Feature

Recently updated colorectal cancer (CRC) screening guidance from the American College of Physicians is raising concerns among some specialists.

The ACP’s clinical guidance, published in Annals of Internal Medicine, called for CRC screenings to start at age 50 in average-risk individuals who are asymptomatic. This recommendation, however, conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which, in 2021, officially lowered the recommended initial age of screening to 45.

Following the ACP’s announcement, several professional organizations, such as the American College of Radiology, criticized the new guidelines, calling them “a step backward” and warning they may hinder recent gains against CRC.

Some physicians believe the discordance will confuse patients and lead to varying referral practices among primary care physicians. And while insurers will likely continue to pay for screening procedures based on the USPSTF guidelines, which dictate insurance coverage, some physicians worry that insurers could create additional roadblocks for CRC screening coverage, such as requiring prior authorization.

“We’re in a conflicted space on this issue as a country,” said John L. Marshall, MD, a GI oncologist and director of The Ruesch Center for the Cure of GI Cancers at Georgetown University, Washington.

Ultimately, the physician community wants an inexpensive screening test that’s effective at preventing cancer and deaths, but the evidence thus far doesn’t necessarily support colonoscopy as that test, said Dr. Marshall, also chief medical officer for Lombardi Comprehensive Cancer Center.

Although colonoscopy can prevent CRC by removing precancerous polyps and can reduce deaths from cancer, it has not been shown to lower all-cause mortality, Dr. Marshall explained. A recent meta-analysis, for example, found that, aside from sigmoidoscopy for colon cancer screening, no other cancer screening modalities meaningfully changed life expectancy.

“That’s why we’re struggling,” Dr. Marshall said. “We’re emotionally invested in having screening available to younger people because we’re seeing colon cancer in younger people. So, we want it to move earlier, but it’s expensive and it’s invasive.”
 

Docs debate differing guidance

The new ACP guidance, based on a critical review of existing guidelines, evidence, and modeling studies, argues that the potential harms of screening average-risk individuals under age 50 may outweigh the potential benefits.

The benefits of screening, of course, include identifying and removing precancerous lesions or localized cancer, while the potential harms include false positives that may lead to unnecessary additional tests, treatments, and costs. More invasive screening procedures, such as colonoscopy, can also come with their own risks, including serious bleeding and perforation.

For colonoscopy, for instance, the ACP team determined that starting screening at age 45 vs. 50 could prevent three additional CRC cases per 1,000 individuals screened (58 vs. 61) and one CRC death (27 vs. 28) over the recommended screening time frame. On the flip side, screening starting at age 45 could increase the incidence of gastrointestinal or cardiovascular events (14 vs. 16).

“Even if we assumed the modeling study had no limitations and accepted the results at face value, we would conclude that the small estimated benefits and harms roughly balance each other out, resulting in an inadequate net benefit to warrant CRC screening in average-risk adults aged 45 to 49 years,” Amir Qaseem, MD, PhD, and ACP coauthors write.

Family physician Kenny Lin, MD, MPH, believes the updated ACP guidelines are reasonable, and points out the ACP is not the first group to disagree with the USPSTF’s recommendations.

“I think the [ACP] guidelines make a lot of sense,” said Dr. Lin, who practices in Lancaster, Pa. The American Academy of Family Physicians “also did not endorse the recommendations to start screenings at 45.” In its 2021 updated guidance, the AAFP recommended screening for CRC starting at age 50, concluding there was “insufficient evidence to assess the benefits and harms of screening” in the 45 to 49 population.

However, Jason R. Woloski, MD, a family physician based in Wilkes-Barre, Pa., expressed concern that the differing guidelines will confuse patients as well as present challenges for primary care physicians.

“I feel like we took the last couple of years convincing people that earlier is better,” said Dr. Woloski, an associate professor of family medicine at Geisinger Commonwealth School of Medicine, Scranton, Pa. “It can send a mixed message to a patient after we’ve been stressing the importance of earlier [screening], and then saying, ‘Maybe we got it wrong; maybe we were okay the first time.’ ”

Mark A. Lewis, MD, a GI oncologist, had a similar initial reaction upon hearing about the updated guidelines: “The lack of synchronization across groups is going to create confusion among patients.”

Although he could not say definitively whether the recommendations will affect GI oncologists, because he only sees patients with advanced CRC, he does see the demands in primary care and gastroenterology shifting.

“I think the much bigger impact will be on primary care physicians and gastroenterologists,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “My best guess is that the procedural burden on the latter will be mitigated by more stool testing ordered by primary care physicians. Patients may understandably prefer the convenience and lack of invasiveness of home-based fecal testing, but a positive FIT [fecal immunochemical test] without a follow-up scope is an incomplete screening.”

Dr. Marshall, however, had a different take. He does not envision the updated guidelines having much of a practical impact on physician practice. Most of the country is already not receiving proper colon cancer screenings, he said. Research shows more than 40% of Americans skip standard CRC screenings. Even anecdotally, he noted, friends in their 60s come to him and admit they haven’t had a colonoscopy yet.
 

Potential impact on patient outcomes, costs

Beyond mixed messaging, some experts worry that pushing CRC screening later could mean cancers are caught later, when they’re more advanced.

Finding cancers earlier, when they are easier and less expensive to treat, make earlier CRC screenings worthwhile, Dr. Woloski explained.

Dr. Lewis sees earlier screening as a way to stop a tumor from progressing before it can really pick up steam.

“To me the biggest advantage of colonoscopy is the interruption of the adenoma-to-carcinoma sequence, whereby a polyp that is completely removed cannot become an invasive adenocarcinoma,” Dr. Lewis said. “We’ve also had evidence for well over a decade that flexible sigmoidoscopy, which doesn’t come close to visualizing the entire colon, can confer a survival benefit.”

Another concern is the potential effect on insurance coverage.

Medicare and other insurers use USPSTF guidelines to make coverage decisions. However, because of this mixed message, Dr. Woloski questioned whether there would be more challenges regarding insurance coverage. “Does it mean primary care doctors are going to have to preauthorize a lot of these screenings even if you have shared decision-making with the patient?” he asked.

When it comes to screening referrals, Douglas A. Corley, MD, PhD, a gastroenterologist at Kaiser Permanente in northern California, said it’s critical for primary care physicians to educate patients about the differing views on screening benefits and harms as well as the different screening options.

“Given the different opinions, it is important to let people in this age group know that screening is an option recommended by some groups,” Dr. Corley said. “Colorectal cancer screening is very effective for decreasing the risk for death from colorectal cancer, which is the second leading cause of cancer death in the United States. Making sure all eligible people know this is an option provides the best way for patients to have an informed choice.”

Dr. Lin has already begun talking with patients about the differing recommendations. He said it’s helpful to simplify the issue and focus the conversation on what patients value most. For more assertive patients whose priority is finding every possible cancer early, starting screenings at age 45 may be reasonable, he said, whereas other patients may not find the process or possible side effects worth it.

“And then you have the middle group that decides, ‘Yes, I want to start at 45, but I want the fecal test. I don’t want to just jump into colonoscopy.’ ” Dr. Lin said. “That would be kind of a compromise where you’d be starting screening earlier, but not subjecting yourself to something that has more potential for harms.”

Dr. Woloski said he plans to continue making referrals based on the USPSTF recommendations.

“With every screening, it is about informed decision-making with the patient, but I think for now, since USPSTF still supports the earlier screening, I will probably stick with offering it earlier,” he said.

But when deciding on the appropriate timing for evaluating CRC, the most important distinction is between screening and diagnosis, Dr. Lewis added.

“The former is only appropriate in patients who are truly asymptomatic and who are truly average-risk,” he said. “The latter is critical in any patient with symptoms. I cannot count the number of times I have seen blood in the stool discounted as hemorrhoids without even an exam, digital rectal, or scope, to demonstrate that hemorrhoids are present and the culprit for blood loss.”

A version of this article first appeared on Medscape.com.

Recently updated colorectal cancer (CRC) screening guidance from the American College of Physicians is raising concerns among some specialists.

The ACP’s clinical guidance, published in Annals of Internal Medicine, called for CRC screenings to start at age 50 in average-risk individuals who are asymptomatic. This recommendation, however, conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which, in 2021, officially lowered the recommended initial age of screening to 45.

Following the ACP’s announcement, several professional organizations, such as the American College of Radiology, criticized the new guidelines, calling them “a step backward” and warning they may hinder recent gains against CRC.

Some physicians believe the discordance will confuse patients and lead to varying referral practices among primary care physicians. And while insurers will likely continue to pay for screening procedures based on the USPSTF guidelines, which dictate insurance coverage, some physicians worry that insurers could create additional roadblocks for CRC screening coverage, such as requiring prior authorization.

“We’re in a conflicted space on this issue as a country,” said John L. Marshall, MD, a GI oncologist and director of The Ruesch Center for the Cure of GI Cancers at Georgetown University, Washington.

Ultimately, the physician community wants an inexpensive screening test that’s effective at preventing cancer and deaths, but the evidence thus far doesn’t necessarily support colonoscopy as that test, said Dr. Marshall, also chief medical officer for Lombardi Comprehensive Cancer Center.

Although colonoscopy can prevent CRC by removing precancerous polyps and can reduce deaths from cancer, it has not been shown to lower all-cause mortality, Dr. Marshall explained. A recent meta-analysis, for example, found that, aside from sigmoidoscopy for colon cancer screening, no other cancer screening modalities meaningfully changed life expectancy.

“That’s why we’re struggling,” Dr. Marshall said. “We’re emotionally invested in having screening available to younger people because we’re seeing colon cancer in younger people. So, we want it to move earlier, but it’s expensive and it’s invasive.”
 

Docs debate differing guidance

The new ACP guidance, based on a critical review of existing guidelines, evidence, and modeling studies, argues that the potential harms of screening average-risk individuals under age 50 may outweigh the potential benefits.

The benefits of screening, of course, include identifying and removing precancerous lesions or localized cancer, while the potential harms include false positives that may lead to unnecessary additional tests, treatments, and costs. More invasive screening procedures, such as colonoscopy, can also come with their own risks, including serious bleeding and perforation.

For colonoscopy, for instance, the ACP team determined that starting screening at age 45 vs. 50 could prevent three additional CRC cases per 1,000 individuals screened (58 vs. 61) and one CRC death (27 vs. 28) over the recommended screening time frame. On the flip side, screening starting at age 45 could increase the incidence of gastrointestinal or cardiovascular events (14 vs. 16).

“Even if we assumed the modeling study had no limitations and accepted the results at face value, we would conclude that the small estimated benefits and harms roughly balance each other out, resulting in an inadequate net benefit to warrant CRC screening in average-risk adults aged 45 to 49 years,” Amir Qaseem, MD, PhD, and ACP coauthors write.

Family physician Kenny Lin, MD, MPH, believes the updated ACP guidelines are reasonable, and points out the ACP is not the first group to disagree with the USPSTF’s recommendations.

“I think the [ACP] guidelines make a lot of sense,” said Dr. Lin, who practices in Lancaster, Pa. The American Academy of Family Physicians “also did not endorse the recommendations to start screenings at 45.” In its 2021 updated guidance, the AAFP recommended screening for CRC starting at age 50, concluding there was “insufficient evidence to assess the benefits and harms of screening” in the 45 to 49 population.

However, Jason R. Woloski, MD, a family physician based in Wilkes-Barre, Pa., expressed concern that the differing guidelines will confuse patients as well as present challenges for primary care physicians.

“I feel like we took the last couple of years convincing people that earlier is better,” said Dr. Woloski, an associate professor of family medicine at Geisinger Commonwealth School of Medicine, Scranton, Pa. “It can send a mixed message to a patient after we’ve been stressing the importance of earlier [screening], and then saying, ‘Maybe we got it wrong; maybe we were okay the first time.’ ”

Mark A. Lewis, MD, a GI oncologist, had a similar initial reaction upon hearing about the updated guidelines: “The lack of synchronization across groups is going to create confusion among patients.”

Although he could not say definitively whether the recommendations will affect GI oncologists, because he only sees patients with advanced CRC, he does see the demands in primary care and gastroenterology shifting.

“I think the much bigger impact will be on primary care physicians and gastroenterologists,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “My best guess is that the procedural burden on the latter will be mitigated by more stool testing ordered by primary care physicians. Patients may understandably prefer the convenience and lack of invasiveness of home-based fecal testing, but a positive FIT [fecal immunochemical test] without a follow-up scope is an incomplete screening.”

Dr. Marshall, however, had a different take. He does not envision the updated guidelines having much of a practical impact on physician practice. Most of the country is already not receiving proper colon cancer screenings, he said. Research shows more than 40% of Americans skip standard CRC screenings. Even anecdotally, he noted, friends in their 60s come to him and admit they haven’t had a colonoscopy yet.
 

Potential impact on patient outcomes, costs

Beyond mixed messaging, some experts worry that pushing CRC screening later could mean cancers are caught later, when they’re more advanced.

Finding cancers earlier, when they are easier and less expensive to treat, make earlier CRC screenings worthwhile, Dr. Woloski explained.

Dr. Lewis sees earlier screening as a way to stop a tumor from progressing before it can really pick up steam.

“To me the biggest advantage of colonoscopy is the interruption of the adenoma-to-carcinoma sequence, whereby a polyp that is completely removed cannot become an invasive adenocarcinoma,” Dr. Lewis said. “We’ve also had evidence for well over a decade that flexible sigmoidoscopy, which doesn’t come close to visualizing the entire colon, can confer a survival benefit.”

Another concern is the potential effect on insurance coverage.

Medicare and other insurers use USPSTF guidelines to make coverage decisions. However, because of this mixed message, Dr. Woloski questioned whether there would be more challenges regarding insurance coverage. “Does it mean primary care doctors are going to have to preauthorize a lot of these screenings even if you have shared decision-making with the patient?” he asked.

When it comes to screening referrals, Douglas A. Corley, MD, PhD, a gastroenterologist at Kaiser Permanente in northern California, said it’s critical for primary care physicians to educate patients about the differing views on screening benefits and harms as well as the different screening options.

“Given the different opinions, it is important to let people in this age group know that screening is an option recommended by some groups,” Dr. Corley said. “Colorectal cancer screening is very effective for decreasing the risk for death from colorectal cancer, which is the second leading cause of cancer death in the United States. Making sure all eligible people know this is an option provides the best way for patients to have an informed choice.”

Dr. Lin has already begun talking with patients about the differing recommendations. He said it’s helpful to simplify the issue and focus the conversation on what patients value most. For more assertive patients whose priority is finding every possible cancer early, starting screenings at age 45 may be reasonable, he said, whereas other patients may not find the process or possible side effects worth it.

“And then you have the middle group that decides, ‘Yes, I want to start at 45, but I want the fecal test. I don’t want to just jump into colonoscopy.’ ” Dr. Lin said. “That would be kind of a compromise where you’d be starting screening earlier, but not subjecting yourself to something that has more potential for harms.”

Dr. Woloski said he plans to continue making referrals based on the USPSTF recommendations.

“With every screening, it is about informed decision-making with the patient, but I think for now, since USPSTF still supports the earlier screening, I will probably stick with offering it earlier,” he said.

But when deciding on the appropriate timing for evaluating CRC, the most important distinction is between screening and diagnosis, Dr. Lewis added.

“The former is only appropriate in patients who are truly asymptomatic and who are truly average-risk,” he said. “The latter is critical in any patient with symptoms. I cannot count the number of times I have seen blood in the stool discounted as hemorrhoids without even an exam, digital rectal, or scope, to demonstrate that hemorrhoids are present and the culprit for blood loss.”

A version of this article first appeared on Medscape.com.

Recently updated colorectal cancer (CRC) screening guidance from the American College of Physicians is raising concerns among some specialists.

The ACP’s clinical guidance, published in Annals of Internal Medicine, called for CRC screenings to start at age 50 in average-risk individuals who are asymptomatic. This recommendation, however, conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which, in 2021, officially lowered the recommended initial age of screening to 45.

Following the ACP’s announcement, several professional organizations, such as the American College of Radiology, criticized the new guidelines, calling them “a step backward” and warning they may hinder recent gains against CRC.

Some physicians believe the discordance will confuse patients and lead to varying referral practices among primary care physicians. And while insurers will likely continue to pay for screening procedures based on the USPSTF guidelines, which dictate insurance coverage, some physicians worry that insurers could create additional roadblocks for CRC screening coverage, such as requiring prior authorization.

“We’re in a conflicted space on this issue as a country,” said John L. Marshall, MD, a GI oncologist and director of The Ruesch Center for the Cure of GI Cancers at Georgetown University, Washington.

Ultimately, the physician community wants an inexpensive screening test that’s effective at preventing cancer and deaths, but the evidence thus far doesn’t necessarily support colonoscopy as that test, said Dr. Marshall, also chief medical officer for Lombardi Comprehensive Cancer Center.

Although colonoscopy can prevent CRC by removing precancerous polyps and can reduce deaths from cancer, it has not been shown to lower all-cause mortality, Dr. Marshall explained. A recent meta-analysis, for example, found that, aside from sigmoidoscopy for colon cancer screening, no other cancer screening modalities meaningfully changed life expectancy.

“That’s why we’re struggling,” Dr. Marshall said. “We’re emotionally invested in having screening available to younger people because we’re seeing colon cancer in younger people. So, we want it to move earlier, but it’s expensive and it’s invasive.”
 

Docs debate differing guidance

The new ACP guidance, based on a critical review of existing guidelines, evidence, and modeling studies, argues that the potential harms of screening average-risk individuals under age 50 may outweigh the potential benefits.

The benefits of screening, of course, include identifying and removing precancerous lesions or localized cancer, while the potential harms include false positives that may lead to unnecessary additional tests, treatments, and costs. More invasive screening procedures, such as colonoscopy, can also come with their own risks, including serious bleeding and perforation.

For colonoscopy, for instance, the ACP team determined that starting screening at age 45 vs. 50 could prevent three additional CRC cases per 1,000 individuals screened (58 vs. 61) and one CRC death (27 vs. 28) over the recommended screening time frame. On the flip side, screening starting at age 45 could increase the incidence of gastrointestinal or cardiovascular events (14 vs. 16).

“Even if we assumed the modeling study had no limitations and accepted the results at face value, we would conclude that the small estimated benefits and harms roughly balance each other out, resulting in an inadequate net benefit to warrant CRC screening in average-risk adults aged 45 to 49 years,” Amir Qaseem, MD, PhD, and ACP coauthors write.

Family physician Kenny Lin, MD, MPH, believes the updated ACP guidelines are reasonable, and points out the ACP is not the first group to disagree with the USPSTF’s recommendations.

“I think the [ACP] guidelines make a lot of sense,” said Dr. Lin, who practices in Lancaster, Pa. The American Academy of Family Physicians “also did not endorse the recommendations to start screenings at 45.” In its 2021 updated guidance, the AAFP recommended screening for CRC starting at age 50, concluding there was “insufficient evidence to assess the benefits and harms of screening” in the 45 to 49 population.

However, Jason R. Woloski, MD, a family physician based in Wilkes-Barre, Pa., expressed concern that the differing guidelines will confuse patients as well as present challenges for primary care physicians.

“I feel like we took the last couple of years convincing people that earlier is better,” said Dr. Woloski, an associate professor of family medicine at Geisinger Commonwealth School of Medicine, Scranton, Pa. “It can send a mixed message to a patient after we’ve been stressing the importance of earlier [screening], and then saying, ‘Maybe we got it wrong; maybe we were okay the first time.’ ”

Mark A. Lewis, MD, a GI oncologist, had a similar initial reaction upon hearing about the updated guidelines: “The lack of synchronization across groups is going to create confusion among patients.”

Although he could not say definitively whether the recommendations will affect GI oncologists, because he only sees patients with advanced CRC, he does see the demands in primary care and gastroenterology shifting.

“I think the much bigger impact will be on primary care physicians and gastroenterologists,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “My best guess is that the procedural burden on the latter will be mitigated by more stool testing ordered by primary care physicians. Patients may understandably prefer the convenience and lack of invasiveness of home-based fecal testing, but a positive FIT [fecal immunochemical test] without a follow-up scope is an incomplete screening.”

Dr. Marshall, however, had a different take. He does not envision the updated guidelines having much of a practical impact on physician practice. Most of the country is already not receiving proper colon cancer screenings, he said. Research shows more than 40% of Americans skip standard CRC screenings. Even anecdotally, he noted, friends in their 60s come to him and admit they haven’t had a colonoscopy yet.
 

Potential impact on patient outcomes, costs

Beyond mixed messaging, some experts worry that pushing CRC screening later could mean cancers are caught later, when they’re more advanced.

Finding cancers earlier, when they are easier and less expensive to treat, make earlier CRC screenings worthwhile, Dr. Woloski explained.

Dr. Lewis sees earlier screening as a way to stop a tumor from progressing before it can really pick up steam.

“To me the biggest advantage of colonoscopy is the interruption of the adenoma-to-carcinoma sequence, whereby a polyp that is completely removed cannot become an invasive adenocarcinoma,” Dr. Lewis said. “We’ve also had evidence for well over a decade that flexible sigmoidoscopy, which doesn’t come close to visualizing the entire colon, can confer a survival benefit.”

Another concern is the potential effect on insurance coverage.

Medicare and other insurers use USPSTF guidelines to make coverage decisions. However, because of this mixed message, Dr. Woloski questioned whether there would be more challenges regarding insurance coverage. “Does it mean primary care doctors are going to have to preauthorize a lot of these screenings even if you have shared decision-making with the patient?” he asked.

When it comes to screening referrals, Douglas A. Corley, MD, PhD, a gastroenterologist at Kaiser Permanente in northern California, said it’s critical for primary care physicians to educate patients about the differing views on screening benefits and harms as well as the different screening options.

“Given the different opinions, it is important to let people in this age group know that screening is an option recommended by some groups,” Dr. Corley said. “Colorectal cancer screening is very effective for decreasing the risk for death from colorectal cancer, which is the second leading cause of cancer death in the United States. Making sure all eligible people know this is an option provides the best way for patients to have an informed choice.”

Dr. Lin has already begun talking with patients about the differing recommendations. He said it’s helpful to simplify the issue and focus the conversation on what patients value most. For more assertive patients whose priority is finding every possible cancer early, starting screenings at age 45 may be reasonable, he said, whereas other patients may not find the process or possible side effects worth it.

“And then you have the middle group that decides, ‘Yes, I want to start at 45, but I want the fecal test. I don’t want to just jump into colonoscopy.’ ” Dr. Lin said. “That would be kind of a compromise where you’d be starting screening earlier, but not subjecting yourself to something that has more potential for harms.”

Dr. Woloski said he plans to continue making referrals based on the USPSTF recommendations.

“With every screening, it is about informed decision-making with the patient, but I think for now, since USPSTF still supports the earlier screening, I will probably stick with offering it earlier,” he said.

But when deciding on the appropriate timing for evaluating CRC, the most important distinction is between screening and diagnosis, Dr. Lewis added.

“The former is only appropriate in patients who are truly asymptomatic and who are truly average-risk,” he said. “The latter is critical in any patient with symptoms. I cannot count the number of times I have seen blood in the stool discounted as hemorrhoids without even an exam, digital rectal, or scope, to demonstrate that hemorrhoids are present and the culprit for blood loss.”

A version of this article first appeared on Medscape.com.

When hematologist James R. Berenson, MD, began practicing medicine in the 1980s, his 45-year-old cousin Stanley broke his ribs while hugging his son in a swimming pool. The cousin was a well-respected orthopedic surgeon in Los Angeles, but his specialty could do nothing for him. Stanley had the bone-ravaging disease known as multiple myeloma (MM).

Back then, the treatments for MM were chemotherapy and steroids. Stem-cell transplants were on the horizon, as was a most unexpected therapy: the infamous drug thalidomide.

But in the wake of the rib facture, the health of Stanley Katz, MD, worsened and he died after 25 weeks, Dr. Berenson recalled in an interview. At that time, Dr. Katz’s horrifically shortened lifespan following diagnosis was not unusual.

About 4 decades later, hematologists like Dr. Berenson are heralding a new era in MM, a sharp reversal of the previous eras of grim prognoses.

In a new study, Dr. Berenson tracked 161 patients with MM treated at his West Hollywood, Calif., private clinic from 2006 to 2023 and found that their median survival was 136.2 months – more than 11 years. “The OS reported in this study ... is the longest reported to date in an unselected, newly diagnosed MM population,” the study authors write.

Dr. Berenson’s patients are unique: They’re largely White, and they didn’t undergo stem-cell transplants. But other recent studies also suggest that lifespans of more than 10 years are increasingly possible after MM diagnosis. Former TV news anchor Tom Brokaw, for one, has reached that point.

In fact, a pair of other hematologists say the overall survival in Dr. Berenson’s report is hardly out of the question. And, they say, patients diagnosed today could potentially live even longer, because treatments continue to improve.

“With data that’s 10 years old, we expect the median overall survival to be 10 years,” hematologist Sagar Lonial, MD, who’s been tracking survival data in MM, said in an interview. “When patients ask about my outlook, I say it’s a constantly evolving field. Things are changing fast enough that I use 10 years as a floor.”

Dr. Lonial is chair of the department of hematology and medical oncology and chief medical officer at Emory University, Atlanta, Winship Cancer Institute.

Hematologist Rafael Fonseca, MD, chief innovation officer at Mayo Clinic–Arizona, put it this way in an interview: Dr. Berenson’s results “are probably in sync with what we would anticipate with similar cohorts of patients. The reality is that we’ve seen a huge improvement in the life expectancy of patients who were diagnosed with multiple myeloma. It’s not unusual to see patients in the clinic now that are 15 or 20 years out from their diagnosis.”

According to Yale Medicine, MM accounts for 10% of blood cancers and 1%-2% of all cancers and is more common in men vs. women and Blacks vs. Whites. It’s most frequently diagnosed between the ages of 65 and 74, according to the National Cancer Institute, and the median age at diagnosis is 69.

Among the most famous American people currently battling MM are newsman Mr. Brokaw, the former NBC News anchor, and Republican Congressman Steve Scalise, majority leader of the U.S. House of Representatives and a candidate for House speaker.

Mr. Brokaw was diagnosed in 2013 while in his early 70s and has talked about his intense struggle with the disease: the infections, operations, infusions, and daily regimens of 24 pills.

“I didn’t want to be Tom Brokaw, cancer victim,” he said in 2018 at the annual meeting of the American Society of Hematology. But he opened up about his illness, and became “the multiple myeloma poster boy.”

Rep. Scalise, who’s in his late 50s, is undergoing chemotherapy. He survived being gravely wounded in an assassination attempt in 2017.

Dr. Berenson’s new study, published in Targeted Oncology, tracked 161 patients (89 women, 72 men; median age, 65.4; 125 White, 3 Black, 10 Hispanic, 15 Asian, and 8 multi-ethnic).

All started frontline treatment at Dr. Berenson’s clinic and were included if they could read consent forms and gave permission for blood draws. None underwent stem-cell transplants as part of initial therapy. Another 1,036 patients had been treated elsewhere and were not included in the study.

Over a median of 42.7 months (range, 1.9-195.1), the 1-, 3-, and 5-year survival rates were 97.5%, 85.3%, and 76.2%, respectively.

The study claims “these results are considerably better than those reported from patients enrolled in clinical trials and those from countries with national registries.”

In the interview, Dr. Berenson said the study is unique because it’s not limited like many studies to younger, healthier patients. Nor does it include those treated at other facilities, he said.

The study is unusual in other ways. Dr. Berenson said his drug regimens aren’t necessarily standard, and he doesn’t treat patients with stem-cell transplants. “I stopped transplanting in about 2000 because clearly it was not improving the length of life,” he said.

Dr. Berenson said colleagues can learn from his insistence on sensitively treating the quality of life of patients, his embrace of clinical trials with novel combinations, and his close monitoring of myeloma proteins to gauge whether patients need to rapidly switch therapies.

He noted that his drug regimens are typically off-label and vary by patient. “We’re not using as high doses of drugs like Velcade [bortezomib] or Revlimid [lenalidomide] as my colleagues. We’re not necessarily giving as many doses. Also, we’re not adding as many drugs in many cases as they are. We’re taking it slower.”

The National Comprehensive Cancer Network recommends bortezomib and lenalidomide as standard induction treatments in patients with MM who are candidates for stem-cell transplantation, a procedure it considers the “preferred approach in transplant-eligible patients.”

There are limitations to Dr. Berenson’s new study. The patients aren’t representative of people with MM as a whole: His cohort is overwhelmingly White (78%) and just 2% Black, while an estimated one-fifth of patients with MM in the United States are Black and have poorer outcomes.

Dr. Berenson also acknowledged that his patients are most likely a wealthier group, although he said it’s not feasible to ask them about income. The study provides no information about socioeconomics.

Dr. Lonial said survival of 10-11 years is fairly typical in MM, with standard-risk patients reaching 14 years.

He highlighted a 2021 Canadian study that tracked 3,030 patients with newly diagnosed MM from 2007 to 2018 (average age, 64; 58.6% men). Those who received an upfront autologous stem-cell transplant had a median overall survival of 122.0 months (95% confidence interval, 115.0-135.0 months) vs. 54.3 months (95% CI, 50.8-58.8 months) for those who didn’t get the transplants. Not surprisingly, survival dipped with each subsequent treatment regimen.

Dr. Lonial is coauthor of a 2020 study that tracked 1,000 consecutive patients (mean age, 61; 35.2% Black) with newly diagnosed myeloma who were treated with RVD (lenalidomide, bortezomib, and dexamethasone) induction therapy from 2007 to 2016. The median overall survival was 126.6 months (95% CI, 113.3-139.8 months).

Dr. Fonseca noted that the news about MM survival rates is not entirely positive. Patients with high-risk disease often die early on in their disease course, he said.

Research suggests even the youngest patients with MM may die within years of diagnosis. A 2021 French study tracked 214 patients in the 18-40 age group for 15 years (2000-2015). At 5 years, “relative survival compared with same age- and sex-matched individuals was 83.5%,” and estimated overall survival was 14.5 years.

Still, a “very, very fertile environment for the development of drugs” has made a huge difference, Dr. Fonseca said. “We’ve had about 19 FDA approvals in the last 15 or 20 years.”

He urged colleagues to keep in mind that survival drops as patients decline in a line of therapy and need to switch to another one. “It might make intuitive sense to say ‘I’m gonna save something for later. I want to keep my powder dry.’ But put your best foot forward. Always go with your best treatments first.”

This approach can play out in a decision, say, to start with a four-drug initial regimen instead of a weaker two-drug regimen, he said. “Be mindful of managing toxicities, but hit harder.”

As he noted, side effects were worse with older generations of drugs. In regard to cost, multidrug treatments can cost hundreds of thousands of dollars. Dr. Fonseca said insurance tends to cover drugs that are approved by guidelines.

Dr. Fonseca discloses relationships with AbbVie, Adaptive Biotechnologies, Amgen, AstraZeneca, Bayer, Binding Site, BMS (Celgene), Millennium Takeda, Janssen, Juno, Kite, Merck, Pfizer, Pharmacyclics, Regeneron, Sanofi, Adaptive Biotechnologies, Caris Life Sciences, Oncotracker, Antegene, and AZBio, and a patent in MM. Dr. Berenson discloses ties with Janssen, Amgen, Sanofi, BMS, Karyopharm, and Incyte. Dr. Lonial reports ties with TG Therapeutics, Celgene, BMS, Janssen, Novartis, GlaxoSmithKline, AbbVie, Takeda, Merck, Sanofi, Pfizer, Regeneron, and Novartis.
 

When hematologist James R. Berenson, MD, began practicing medicine in the 1980s, his 45-year-old cousin Stanley broke his ribs while hugging his son in a swimming pool. The cousin was a well-respected orthopedic surgeon in Los Angeles, but his specialty could do nothing for him. Stanley had the bone-ravaging disease known as multiple myeloma (MM).

Back then, the treatments for MM were chemotherapy and steroids. Stem-cell transplants were on the horizon, as was a most unexpected therapy: the infamous drug thalidomide.

But in the wake of the rib facture, the health of Stanley Katz, MD, worsened and he died after 25 weeks, Dr. Berenson recalled in an interview. At that time, Dr. Katz’s horrifically shortened lifespan following diagnosis was not unusual.

About 4 decades later, hematologists like Dr. Berenson are heralding a new era in MM, a sharp reversal of the previous eras of grim prognoses.

In a new study, Dr. Berenson tracked 161 patients with MM treated at his West Hollywood, Calif., private clinic from 2006 to 2023 and found that their median survival was 136.2 months – more than 11 years. “The OS reported in this study ... is the longest reported to date in an unselected, newly diagnosed MM population,” the study authors write.

Dr. Berenson’s patients are unique: They’re largely White, and they didn’t undergo stem-cell transplants. But other recent studies also suggest that lifespans of more than 10 years are increasingly possible after MM diagnosis. Former TV news anchor Tom Brokaw, for one, has reached that point.

In fact, a pair of other hematologists say the overall survival in Dr. Berenson’s report is hardly out of the question. And, they say, patients diagnosed today could potentially live even longer, because treatments continue to improve.

“With data that’s 10 years old, we expect the median overall survival to be 10 years,” hematologist Sagar Lonial, MD, who’s been tracking survival data in MM, said in an interview. “When patients ask about my outlook, I say it’s a constantly evolving field. Things are changing fast enough that I use 10 years as a floor.”

Dr. Lonial is chair of the department of hematology and medical oncology and chief medical officer at Emory University, Atlanta, Winship Cancer Institute.

Hematologist Rafael Fonseca, MD, chief innovation officer at Mayo Clinic–Arizona, put it this way in an interview: Dr. Berenson’s results “are probably in sync with what we would anticipate with similar cohorts of patients. The reality is that we’ve seen a huge improvement in the life expectancy of patients who were diagnosed with multiple myeloma. It’s not unusual to see patients in the clinic now that are 15 or 20 years out from their diagnosis.”

According to Yale Medicine, MM accounts for 10% of blood cancers and 1%-2% of all cancers and is more common in men vs. women and Blacks vs. Whites. It’s most frequently diagnosed between the ages of 65 and 74, according to the National Cancer Institute, and the median age at diagnosis is 69.

Among the most famous American people currently battling MM are newsman Mr. Brokaw, the former NBC News anchor, and Republican Congressman Steve Scalise, majority leader of the U.S. House of Representatives and a candidate for House speaker.

Mr. Brokaw was diagnosed in 2013 while in his early 70s and has talked about his intense struggle with the disease: the infections, operations, infusions, and daily regimens of 24 pills.

“I didn’t want to be Tom Brokaw, cancer victim,” he said in 2018 at the annual meeting of the American Society of Hematology. But he opened up about his illness, and became “the multiple myeloma poster boy.”

Rep. Scalise, who’s in his late 50s, is undergoing chemotherapy. He survived being gravely wounded in an assassination attempt in 2017.

Dr. Berenson’s new study, published in Targeted Oncology, tracked 161 patients (89 women, 72 men; median age, 65.4; 125 White, 3 Black, 10 Hispanic, 15 Asian, and 8 multi-ethnic).

All started frontline treatment at Dr. Berenson’s clinic and were included if they could read consent forms and gave permission for blood draws. None underwent stem-cell transplants as part of initial therapy. Another 1,036 patients had been treated elsewhere and were not included in the study.

Over a median of 42.7 months (range, 1.9-195.1), the 1-, 3-, and 5-year survival rates were 97.5%, 85.3%, and 76.2%, respectively.

The study claims “these results are considerably better than those reported from patients enrolled in clinical trials and those from countries with national registries.”

In the interview, Dr. Berenson said the study is unique because it’s not limited like many studies to younger, healthier patients. Nor does it include those treated at other facilities, he said.

The study is unusual in other ways. Dr. Berenson said his drug regimens aren’t necessarily standard, and he doesn’t treat patients with stem-cell transplants. “I stopped transplanting in about 2000 because clearly it was not improving the length of life,” he said.

Dr. Berenson said colleagues can learn from his insistence on sensitively treating the quality of life of patients, his embrace of clinical trials with novel combinations, and his close monitoring of myeloma proteins to gauge whether patients need to rapidly switch therapies.

He noted that his drug regimens are typically off-label and vary by patient. “We’re not using as high doses of drugs like Velcade [bortezomib] or Revlimid [lenalidomide] as my colleagues. We’re not necessarily giving as many doses. Also, we’re not adding as many drugs in many cases as they are. We’re taking it slower.”

The National Comprehensive Cancer Network recommends bortezomib and lenalidomide as standard induction treatments in patients with MM who are candidates for stem-cell transplantation, a procedure it considers the “preferred approach in transplant-eligible patients.”

There are limitations to Dr. Berenson’s new study. The patients aren’t representative of people with MM as a whole: His cohort is overwhelmingly White (78%) and just 2% Black, while an estimated one-fifth of patients with MM in the United States are Black and have poorer outcomes.

Dr. Berenson also acknowledged that his patients are most likely a wealthier group, although he said it’s not feasible to ask them about income. The study provides no information about socioeconomics.

Dr. Lonial said survival of 10-11 years is fairly typical in MM, with standard-risk patients reaching 14 years.

He highlighted a 2021 Canadian study that tracked 3,030 patients with newly diagnosed MM from 2007 to 2018 (average age, 64; 58.6% men). Those who received an upfront autologous stem-cell transplant had a median overall survival of 122.0 months (95% confidence interval, 115.0-135.0 months) vs. 54.3 months (95% CI, 50.8-58.8 months) for those who didn’t get the transplants. Not surprisingly, survival dipped with each subsequent treatment regimen.

Dr. Lonial is coauthor of a 2020 study that tracked 1,000 consecutive patients (mean age, 61; 35.2% Black) with newly diagnosed myeloma who were treated with RVD (lenalidomide, bortezomib, and dexamethasone) induction therapy from 2007 to 2016. The median overall survival was 126.6 months (95% CI, 113.3-139.8 months).

Dr. Fonseca noted that the news about MM survival rates is not entirely positive. Patients with high-risk disease often die early on in their disease course, he said.

Research suggests even the youngest patients with MM may die within years of diagnosis. A 2021 French study tracked 214 patients in the 18-40 age group for 15 years (2000-2015). At 5 years, “relative survival compared with same age- and sex-matched individuals was 83.5%,” and estimated overall survival was 14.5 years.

Still, a “very, very fertile environment for the development of drugs” has made a huge difference, Dr. Fonseca said. “We’ve had about 19 FDA approvals in the last 15 or 20 years.”

He urged colleagues to keep in mind that survival drops as patients decline in a line of therapy and need to switch to another one. “It might make intuitive sense to say ‘I’m gonna save something for later. I want to keep my powder dry.’ But put your best foot forward. Always go with your best treatments first.”

This approach can play out in a decision, say, to start with a four-drug initial regimen instead of a weaker two-drug regimen, he said. “Be mindful of managing toxicities, but hit harder.”

As he noted, side effects were worse with older generations of drugs. In regard to cost, multidrug treatments can cost hundreds of thousands of dollars. Dr. Fonseca said insurance tends to cover drugs that are approved by guidelines.

Dr. Fonseca discloses relationships with AbbVie, Adaptive Biotechnologies, Amgen, AstraZeneca, Bayer, Binding Site, BMS (Celgene), Millennium Takeda, Janssen, Juno, Kite, Merck, Pfizer, Pharmacyclics, Regeneron, Sanofi, Adaptive Biotechnologies, Caris Life Sciences, Oncotracker, Antegene, and AZBio, and a patent in MM. Dr. Berenson discloses ties with Janssen, Amgen, Sanofi, BMS, Karyopharm, and Incyte. Dr. Lonial reports ties with TG Therapeutics, Celgene, BMS, Janssen, Novartis, GlaxoSmithKline, AbbVie, Takeda, Merck, Sanofi, Pfizer, Regeneron, and Novartis.
 

When hematologist James R. Berenson, MD, began practicing medicine in the 1980s, his 45-year-old cousin Stanley broke his ribs while hugging his son in a swimming pool. The cousin was a well-respected orthopedic surgeon in Los Angeles, but his specialty could do nothing for him. Stanley had the bone-ravaging disease known as multiple myeloma (MM).

Back then, the treatments for MM were chemotherapy and steroids. Stem-cell transplants were on the horizon, as was a most unexpected therapy: the infamous drug thalidomide.

But in the wake of the rib facture, the health of Stanley Katz, MD, worsened and he died after 25 weeks, Dr. Berenson recalled in an interview. At that time, Dr. Katz’s horrifically shortened lifespan following diagnosis was not unusual.

About 4 decades later, hematologists like Dr. Berenson are heralding a new era in MM, a sharp reversal of the previous eras of grim prognoses.

In a new study, Dr. Berenson tracked 161 patients with MM treated at his West Hollywood, Calif., private clinic from 2006 to 2023 and found that their median survival was 136.2 months – more than 11 years. “The OS reported in this study ... is the longest reported to date in an unselected, newly diagnosed MM population,” the study authors write.

Dr. Berenson’s patients are unique: They’re largely White, and they didn’t undergo stem-cell transplants. But other recent studies also suggest that lifespans of more than 10 years are increasingly possible after MM diagnosis. Former TV news anchor Tom Brokaw, for one, has reached that point.

In fact, a pair of other hematologists say the overall survival in Dr. Berenson’s report is hardly out of the question. And, they say, patients diagnosed today could potentially live even longer, because treatments continue to improve.

“With data that’s 10 years old, we expect the median overall survival to be 10 years,” hematologist Sagar Lonial, MD, who’s been tracking survival data in MM, said in an interview. “When patients ask about my outlook, I say it’s a constantly evolving field. Things are changing fast enough that I use 10 years as a floor.”

Dr. Lonial is chair of the department of hematology and medical oncology and chief medical officer at Emory University, Atlanta, Winship Cancer Institute.

Hematologist Rafael Fonseca, MD, chief innovation officer at Mayo Clinic–Arizona, put it this way in an interview: Dr. Berenson’s results “are probably in sync with what we would anticipate with similar cohorts of patients. The reality is that we’ve seen a huge improvement in the life expectancy of patients who were diagnosed with multiple myeloma. It’s not unusual to see patients in the clinic now that are 15 or 20 years out from their diagnosis.”

According to Yale Medicine, MM accounts for 10% of blood cancers and 1%-2% of all cancers and is more common in men vs. women and Blacks vs. Whites. It’s most frequently diagnosed between the ages of 65 and 74, according to the National Cancer Institute, and the median age at diagnosis is 69.

Among the most famous American people currently battling MM are newsman Mr. Brokaw, the former NBC News anchor, and Republican Congressman Steve Scalise, majority leader of the U.S. House of Representatives and a candidate for House speaker.

Mr. Brokaw was diagnosed in 2013 while in his early 70s and has talked about his intense struggle with the disease: the infections, operations, infusions, and daily regimens of 24 pills.

“I didn’t want to be Tom Brokaw, cancer victim,” he said in 2018 at the annual meeting of the American Society of Hematology. But he opened up about his illness, and became “the multiple myeloma poster boy.”

Rep. Scalise, who’s in his late 50s, is undergoing chemotherapy. He survived being gravely wounded in an assassination attempt in 2017.

Dr. Berenson’s new study, published in Targeted Oncology, tracked 161 patients (89 women, 72 men; median age, 65.4; 125 White, 3 Black, 10 Hispanic, 15 Asian, and 8 multi-ethnic).

All started frontline treatment at Dr. Berenson’s clinic and were included if they could read consent forms and gave permission for blood draws. None underwent stem-cell transplants as part of initial therapy. Another 1,036 patients had been treated elsewhere and were not included in the study.

Over a median of 42.7 months (range, 1.9-195.1), the 1-, 3-, and 5-year survival rates were 97.5%, 85.3%, and 76.2%, respectively.

The study claims “these results are considerably better than those reported from patients enrolled in clinical trials and those from countries with national registries.”

In the interview, Dr. Berenson said the study is unique because it’s not limited like many studies to younger, healthier patients. Nor does it include those treated at other facilities, he said.

The study is unusual in other ways. Dr. Berenson said his drug regimens aren’t necessarily standard, and he doesn’t treat patients with stem-cell transplants. “I stopped transplanting in about 2000 because clearly it was not improving the length of life,” he said.

Dr. Berenson said colleagues can learn from his insistence on sensitively treating the quality of life of patients, his embrace of clinical trials with novel combinations, and his close monitoring of myeloma proteins to gauge whether patients need to rapidly switch therapies.

He noted that his drug regimens are typically off-label and vary by patient. “We’re not using as high doses of drugs like Velcade [bortezomib] or Revlimid [lenalidomide] as my colleagues. We’re not necessarily giving as many doses. Also, we’re not adding as many drugs in many cases as they are. We’re taking it slower.”

The National Comprehensive Cancer Network recommends bortezomib and lenalidomide as standard induction treatments in patients with MM who are candidates for stem-cell transplantation, a procedure it considers the “preferred approach in transplant-eligible patients.”

There are limitations to Dr. Berenson’s new study. The patients aren’t representative of people with MM as a whole: His cohort is overwhelmingly White (78%) and just 2% Black, while an estimated one-fifth of patients with MM in the United States are Black and have poorer outcomes.

Dr. Berenson also acknowledged that his patients are most likely a wealthier group, although he said it’s not feasible to ask them about income. The study provides no information about socioeconomics.

Dr. Lonial said survival of 10-11 years is fairly typical in MM, with standard-risk patients reaching 14 years.

He highlighted a 2021 Canadian study that tracked 3,030 patients with newly diagnosed MM from 2007 to 2018 (average age, 64; 58.6% men). Those who received an upfront autologous stem-cell transplant had a median overall survival of 122.0 months (95% confidence interval, 115.0-135.0 months) vs. 54.3 months (95% CI, 50.8-58.8 months) for those who didn’t get the transplants. Not surprisingly, survival dipped with each subsequent treatment regimen.

Dr. Lonial is coauthor of a 2020 study that tracked 1,000 consecutive patients (mean age, 61; 35.2% Black) with newly diagnosed myeloma who were treated with RVD (lenalidomide, bortezomib, and dexamethasone) induction therapy from 2007 to 2016. The median overall survival was 126.6 months (95% CI, 113.3-139.8 months).

Dr. Fonseca noted that the news about MM survival rates is not entirely positive. Patients with high-risk disease often die early on in their disease course, he said.

Research suggests even the youngest patients with MM may die within years of diagnosis. A 2021 French study tracked 214 patients in the 18-40 age group for 15 years (2000-2015). At 5 years, “relative survival compared with same age- and sex-matched individuals was 83.5%,” and estimated overall survival was 14.5 years.

Still, a “very, very fertile environment for the development of drugs” has made a huge difference, Dr. Fonseca said. “We’ve had about 19 FDA approvals in the last 15 or 20 years.”

He urged colleagues to keep in mind that survival drops as patients decline in a line of therapy and need to switch to another one. “It might make intuitive sense to say ‘I’m gonna save something for later. I want to keep my powder dry.’ But put your best foot forward. Always go with your best treatments first.”

This approach can play out in a decision, say, to start with a four-drug initial regimen instead of a weaker two-drug regimen, he said. “Be mindful of managing toxicities, but hit harder.”

As he noted, side effects were worse with older generations of drugs. In regard to cost, multidrug treatments can cost hundreds of thousands of dollars. Dr. Fonseca said insurance tends to cover drugs that are approved by guidelines.

Dr. Fonseca discloses relationships with AbbVie, Adaptive Biotechnologies, Amgen, AstraZeneca, Bayer, Binding Site, BMS (Celgene), Millennium Takeda, Janssen, Juno, Kite, Merck, Pfizer, Pharmacyclics, Regeneron, Sanofi, Adaptive Biotechnologies, Caris Life Sciences, Oncotracker, Antegene, and AZBio, and a patent in MM. Dr. Berenson discloses ties with Janssen, Amgen, Sanofi, BMS, Karyopharm, and Incyte. Dr. Lonial reports ties with TG Therapeutics, Celgene, BMS, Janssen, Novartis, GlaxoSmithKline, AbbVie, Takeda, Merck, Sanofi, Pfizer, Regeneron, and Novartis.
 

Before he attended medical school, Thomas O’Connor, MD, had a not-very-well-kept secret: As a competitive powerlifter, he had used steroids to build strength.

Now an internist and clinical instructor of medicine at the University of Connecticut, Farmington, Dr. O’Connor’s practice focuses on the needs of men taking testosterone and other anabolic steroids – a group he feels is poorly understood and largely neglected by conventional medical care, perceptions borne out by a 2020 study of steroid users he helped conduct.

“They felt discriminated against, they did not feel comfortable working with their physicians, and they felt that the doctors did not know what they were doing,” Dr. O’Connor said in an interview. His patients often express anger and frustration with doctors they had seen previously.
 

Patients turning to home tests

Not surprisingly, then, many users of illegal anabolic-androgenic steroids (AAS) have adopted a DIY approach to monitoring the side effects of the drugs, turning to direct-to-consumer laboratory tests. Clients can order a panel of labs designed to screen for health conditions commonly associated with use of AAS, such as dyslipidemia, renal and hepatic dysfunction, polycythemia, thrombosis, and insulin resistance. The panels also include tests for levels of different hormones.

Sales of direct-to-consumer tests topped $3.6 billion in the United States in 2022 and are predicted to grow. Some of that spending is coming from people, mostly men, using illegally obtained steroids to build muscle. Although published data on the size of the bodybuilder market are unavailable, the Internet is a ready source of relatively inexpensive tests aimed at helping individuals monitor their health.  

While clinicians may have their doubts about allowing patients to pick and choose tests and interpret their results, proponents claim they empower consumers to take control of their health – and save themselves money in the process.

But a test panel designed to help the user monitor the effects of banned substances is a bit unnerving to many clinicians, including Dr. O’Connor.

“People using anabolic steroids should be aware of the health risks associated with such use and that laboratory analysis is an important step toward improving health outcomes,” he said, “I’m all about open education, but not self-diagnosis and treatment.” 

Testosterone and other AAS such as nandrolone, trenbolone, and boldenone are Schedule III controlled substances that have been banned by numerous athletic governing bodies. Yet recreational users can easily obtain them from online international pharmacies without a prescription. Should they be monitoring themselves for side effects?

A basic problem is that few primary care clinicians routinely ask their patients about the use of AAS or feel competent to manage the complications or withdrawal symptoms associated with the agents. And they may have no idea what the average AAS user looks like.

The American College of Sports Medicine updated its statement on the use of AAS in 2021. The statement warned of a growing new segment of users – up to 70% of people who take the drugs do so recreationally in pursuit of a more muscular appearance, rather than competitive athletes seeking enhanced performance.

The ACSM highlighted the syndrome of muscle dysmorphia, also known as “megarexia” or “bigorexia” (think of it as “reverse anorexia”), as a major risk factor for illicit use of AAS.

Stuart Phillips, PhD, professor and director of the department of kinesiology at McMaster University, Hamilton, Ont., coauthored the ACSM guidelines. 

“The prince in Snow White circa 1950s was a guy with nice hair,” said Dr. Phillips, pointing to a change in cultural expectations for the male body. “But then fast forward to the prince or hero in any other Disney movie recently – and the guy is jacked.”

Since the last guidelines were published in 1987, Dr. Phillips has seen some cultural shifts. Testosterone has gone from a banned substance no one talked about to a mainstream medical therapy for men with low androgen levels, as any television viewer of primetime sports can attest. “But the other thing that’s changed,” he added, “is that we’ve seen the proliferation of illicit anabolic steroid use solely for the purpose of aesthetics.”

As an adolescent medicine physician who specializes in eating disorders, Jason Nagata, MD, MSc, sees many young men in his practice who engage in different behaviors to increase their muscle mass – from exercising, consuming high protein diets or taking protein supplements, even injecting AAS.

“A third of teenage boys across the U.S. report they’re trying to gain weight to bulk up and gain muscle,” said Dr. Nagata, an associate professor of pediatrics at the University of California, San Francisco.

In a 2020 study published in JAMA Pediatrics, Dr. Nagata and colleagues found that use of legal performance-enhancing substances in young men aged 18-26 years was associated with a higher odds of using AAS 7 years later (adjusted odds ratio, 3.18; 95% confidence interval, 1.90-5.32). “Some of the legal performance-enhancing substances like the protein powders or creatine may serve as a gateway to use of AAS,” Dr. Nagata said.  

Another important factor is exposure to AAS use on social media, where muscular influencers gain huge followings. Dr. Nagata said most of the research on eating disorders and social media has examined the role of media on weight loss in girls.

“Although there’s less research on the social media impact on boys and men, a few studies have shown links between more Instagram use and muscle dissatisfaction, as well as thinking about using steroids,” he said.

The number of people using AAS is not trivial. In a longitudinal study (led by Nagata) of young U.S. adults surveyed multiple times between 1994 and 2002, a total of 2.7% of 18- to 26-year-old men and 0.4% of women reported using AAS. In a more recent cohort of adolescents in Minnesota aged 14-22 years followed between 2010 and 2018, a total of 2.2% of males and 1% of females initiated AAS use. 

The Endocrine Society has estimated that between 2.9 and 4 million Americans have used an AAS at some point in their lives. Given that use is illegal without a prescription, a limitation of any survey is that participants may not be willing to disclose their AAS habit, leading to an underestimate of the actual number.

Nor are the complications of AAS use negligible. The drugs can have wide-ranging effects on the body, potentially affecting the brain, heart, liver, kidneys, musculoskeletal system, immune system, and reproductive systems. And individuals might unknowingly expose themselves to AAS: A recent literature review found that over a quarter of dietary supplements tested were found to contain undeclared substances that are on the World Anti-Doping Agency’s list of banned agents.
 

Alarming mistrust of MDs

Dr. O’Connor’s study shed some light on why AAS users might resort to surfing the Internet looking for a way to diagnose their own complications from steroid use. The web-based survey of nearly 2,400 men who said they took the drugs found that participants considered physicians to be the worst source of information, ranking them below coaches, online bodybuilding forums and sites, other AAS users, and bodybuilding books or magazines. The majority (56%) did not reveal AAS use to their clinicians. Of those who did, 55% reported feeling discriminated against for the admission.

Dr. O’Connor said physicians receive scant education on the many different drugs and regimens used by bodybuilders and have no idea how to a manage withdrawal syndrome for people trying to get off steroids. He urged the medical community to develop an educational campaign for clinicians, similar to those from public health officials aimed at combating the opioid epidemic: “Let’s educate med students and the residents. Let’s put [steroid use] on our agenda.”
 

Consumer testing evangelist ... or physician nemesis?

Nelson Vergel, BSChE, MBA, is on a mission to make medical lab testing affordable and accessible to everyone. The chemical engineer founded Discounted Labs 8 years ago, offering commonly ordered tests, such as complete blood counts, liver function tests, and cholesterol levels.

Mr. Vergel has advocated for the use of hormones to treat HIV-wasting disease for nearly 40 years, after his own diagnosis of the infection in 1986. After losing 40 pounds, steroids saved his life, he said.

Mr. Vergel said he was shocked to learn about the lack of continuing medical education on AAS for physicians and agreed with Dr. O’Connor that more training is needed for the medical profession. He also recognized that stigma on the part of clinicians is a huge barrier for many AAS users.

“We have to accept the fact that people are using them instead of demonizing them,” Mr. Vergel said. “What I was seeing is that there was so much stigma – and patients would not even talk to their doctors about their use.”

After reviewing Google analytics for his lab’s website and seeing how often “bodybuilder” came up as a search term, he added a panel of labs a year ago that allows AAS users to monitor themselves for adverse events.

Although he doesn’t condone the use of AAS without a medical indication and advises customers to discuss their results with a doctor, “we have to make sure people are reducing their harm or risk,” he said. “That’s really my goal.”

Many health care professionals would disagree with that statement. Dr. Nagata said he was concerned that management of side effects is too complicated. “There are a lot of nuances in the interpretation of these tests.” Arriving at the correct interpretation of the results requires a clinician’s thorough review of each patient’s health history, family history, and mental health history along with lab results. 
 

‘I’m concerned’

In a second article outlining harm-reduction strategies designed to improve care for patients using AAS, Dr. O’Connor and colleagues outlined an approach for talking with patients who are concerned about their health and are seeking guidance from a clinician.

The first step is to work on developing a rapport, and not to demand that patients stop their use of AAS. His recommended opening line is: “I want to be honest with you – I’m concerned.”

The initial interaction is an opportunity to find out why the person uses AAS, what health concerns they have at present, and why they are seeking care. Open-ended questions may reveal concerns that the patient has about fertility or side effects.

Consistent with harm-reduction approaches used for other public health epidemics – such as opioid abuse and blood-borne pathogens among people who inject drugs – follow-up visits can include nonjudgmental discussions about decreasing or stopping their use.

Ultimately, minimizing the harms of AAS use can serve as a bridge to their cessation, but the medical community needs to build up trust with a community of users who currently rely more on each other and the Internet for guidance than their primary care physicians. “We need more education. We’re going to need resources to do it,” Dr. O’Connell said. “And we’re going to have to do it.”

Dr. Phillips and Dr. Nagata have no financial disclosures. Mr. Vergel is the owner and founder of Discounted Labs but reported no other financial conflicts. Dr. O’Connor owns Anabolic Doc but has no additional financial disclosures.

A version of this article first appeared on Medscape.com.

Before he attended medical school, Thomas O’Connor, MD, had a not-very-well-kept secret: As a competitive powerlifter, he had used steroids to build strength.

Now an internist and clinical instructor of medicine at the University of Connecticut, Farmington, Dr. O’Connor’s practice focuses on the needs of men taking testosterone and other anabolic steroids – a group he feels is poorly understood and largely neglected by conventional medical care, perceptions borne out by a 2020 study of steroid users he helped conduct.

“They felt discriminated against, they did not feel comfortable working with their physicians, and they felt that the doctors did not know what they were doing,” Dr. O’Connor said in an interview. His patients often express anger and frustration with doctors they had seen previously.
 

Patients turning to home tests

Not surprisingly, then, many users of illegal anabolic-androgenic steroids (AAS) have adopted a DIY approach to monitoring the side effects of the drugs, turning to direct-to-consumer laboratory tests. Clients can order a panel of labs designed to screen for health conditions commonly associated with use of AAS, such as dyslipidemia, renal and hepatic dysfunction, polycythemia, thrombosis, and insulin resistance. The panels also include tests for levels of different hormones.

Sales of direct-to-consumer tests topped $3.6 billion in the United States in 2022 and are predicted to grow. Some of that spending is coming from people, mostly men, using illegally obtained steroids to build muscle. Although published data on the size of the bodybuilder market are unavailable, the Internet is a ready source of relatively inexpensive tests aimed at helping individuals monitor their health.  

While clinicians may have their doubts about allowing patients to pick and choose tests and interpret their results, proponents claim they empower consumers to take control of their health – and save themselves money in the process.

But a test panel designed to help the user monitor the effects of banned substances is a bit unnerving to many clinicians, including Dr. O’Connor.

“People using anabolic steroids should be aware of the health risks associated with such use and that laboratory analysis is an important step toward improving health outcomes,” he said, “I’m all about open education, but not self-diagnosis and treatment.” 

Testosterone and other AAS such as nandrolone, trenbolone, and boldenone are Schedule III controlled substances that have been banned by numerous athletic governing bodies. Yet recreational users can easily obtain them from online international pharmacies without a prescription. Should they be monitoring themselves for side effects?

A basic problem is that few primary care clinicians routinely ask their patients about the use of AAS or feel competent to manage the complications or withdrawal symptoms associated with the agents. And they may have no idea what the average AAS user looks like.

The American College of Sports Medicine updated its statement on the use of AAS in 2021. The statement warned of a growing new segment of users – up to 70% of people who take the drugs do so recreationally in pursuit of a more muscular appearance, rather than competitive athletes seeking enhanced performance.

The ACSM highlighted the syndrome of muscle dysmorphia, also known as “megarexia” or “bigorexia” (think of it as “reverse anorexia”), as a major risk factor for illicit use of AAS.

Stuart Phillips, PhD, professor and director of the department of kinesiology at McMaster University, Hamilton, Ont., coauthored the ACSM guidelines. 

“The prince in Snow White circa 1950s was a guy with nice hair,” said Dr. Phillips, pointing to a change in cultural expectations for the male body. “But then fast forward to the prince or hero in any other Disney movie recently – and the guy is jacked.”

Since the last guidelines were published in 1987, Dr. Phillips has seen some cultural shifts. Testosterone has gone from a banned substance no one talked about to a mainstream medical therapy for men with low androgen levels, as any television viewer of primetime sports can attest. “But the other thing that’s changed,” he added, “is that we’ve seen the proliferation of illicit anabolic steroid use solely for the purpose of aesthetics.”

As an adolescent medicine physician who specializes in eating disorders, Jason Nagata, MD, MSc, sees many young men in his practice who engage in different behaviors to increase their muscle mass – from exercising, consuming high protein diets or taking protein supplements, even injecting AAS.

“A third of teenage boys across the U.S. report they’re trying to gain weight to bulk up and gain muscle,” said Dr. Nagata, an associate professor of pediatrics at the University of California, San Francisco.

In a 2020 study published in JAMA Pediatrics, Dr. Nagata and colleagues found that use of legal performance-enhancing substances in young men aged 18-26 years was associated with a higher odds of using AAS 7 years later (adjusted odds ratio, 3.18; 95% confidence interval, 1.90-5.32). “Some of the legal performance-enhancing substances like the protein powders or creatine may serve as a gateway to use of AAS,” Dr. Nagata said.  

Another important factor is exposure to AAS use on social media, where muscular influencers gain huge followings. Dr. Nagata said most of the research on eating disorders and social media has examined the role of media on weight loss in girls.

“Although there’s less research on the social media impact on boys and men, a few studies have shown links between more Instagram use and muscle dissatisfaction, as well as thinking about using steroids,” he said.

The number of people using AAS is not trivial. In a longitudinal study (led by Nagata) of young U.S. adults surveyed multiple times between 1994 and 2002, a total of 2.7% of 18- to 26-year-old men and 0.4% of women reported using AAS. In a more recent cohort of adolescents in Minnesota aged 14-22 years followed between 2010 and 2018, a total of 2.2% of males and 1% of females initiated AAS use. 

The Endocrine Society has estimated that between 2.9 and 4 million Americans have used an AAS at some point in their lives. Given that use is illegal without a prescription, a limitation of any survey is that participants may not be willing to disclose their AAS habit, leading to an underestimate of the actual number.

Nor are the complications of AAS use negligible. The drugs can have wide-ranging effects on the body, potentially affecting the brain, heart, liver, kidneys, musculoskeletal system, immune system, and reproductive systems. And individuals might unknowingly expose themselves to AAS: A recent literature review found that over a quarter of dietary supplements tested were found to contain undeclared substances that are on the World Anti-Doping Agency’s list of banned agents.
 

Alarming mistrust of MDs

Dr. O’Connor’s study shed some light on why AAS users might resort to surfing the Internet looking for a way to diagnose their own complications from steroid use. The web-based survey of nearly 2,400 men who said they took the drugs found that participants considered physicians to be the worst source of information, ranking them below coaches, online bodybuilding forums and sites, other AAS users, and bodybuilding books or magazines. The majority (56%) did not reveal AAS use to their clinicians. Of those who did, 55% reported feeling discriminated against for the admission.

Dr. O’Connor said physicians receive scant education on the many different drugs and regimens used by bodybuilders and have no idea how to a manage withdrawal syndrome for people trying to get off steroids. He urged the medical community to develop an educational campaign for clinicians, similar to those from public health officials aimed at combating the opioid epidemic: “Let’s educate med students and the residents. Let’s put [steroid use] on our agenda.”
 

Consumer testing evangelist ... or physician nemesis?

Nelson Vergel, BSChE, MBA, is on a mission to make medical lab testing affordable and accessible to everyone. The chemical engineer founded Discounted Labs 8 years ago, offering commonly ordered tests, such as complete blood counts, liver function tests, and cholesterol levels.

Mr. Vergel has advocated for the use of hormones to treat HIV-wasting disease for nearly 40 years, after his own diagnosis of the infection in 1986. After losing 40 pounds, steroids saved his life, he said.

Mr. Vergel said he was shocked to learn about the lack of continuing medical education on AAS for physicians and agreed with Dr. O’Connor that more training is needed for the medical profession. He also recognized that stigma on the part of clinicians is a huge barrier for many AAS users.

“We have to accept the fact that people are using them instead of demonizing them,” Mr. Vergel said. “What I was seeing is that there was so much stigma – and patients would not even talk to their doctors about their use.”

After reviewing Google analytics for his lab’s website and seeing how often “bodybuilder” came up as a search term, he added a panel of labs a year ago that allows AAS users to monitor themselves for adverse events.

Although he doesn’t condone the use of AAS without a medical indication and advises customers to discuss their results with a doctor, “we have to make sure people are reducing their harm or risk,” he said. “That’s really my goal.”

Many health care professionals would disagree with that statement. Dr. Nagata said he was concerned that management of side effects is too complicated. “There are a lot of nuances in the interpretation of these tests.” Arriving at the correct interpretation of the results requires a clinician’s thorough review of each patient’s health history, family history, and mental health history along with lab results. 
 

‘I’m concerned’

In a second article outlining harm-reduction strategies designed to improve care for patients using AAS, Dr. O’Connor and colleagues outlined an approach for talking with patients who are concerned about their health and are seeking guidance from a clinician.

The first step is to work on developing a rapport, and not to demand that patients stop their use of AAS. His recommended opening line is: “I want to be honest with you – I’m concerned.”

The initial interaction is an opportunity to find out why the person uses AAS, what health concerns they have at present, and why they are seeking care. Open-ended questions may reveal concerns that the patient has about fertility or side effects.

Consistent with harm-reduction approaches used for other public health epidemics – such as opioid abuse and blood-borne pathogens among people who inject drugs – follow-up visits can include nonjudgmental discussions about decreasing or stopping their use.

Ultimately, minimizing the harms of AAS use can serve as a bridge to their cessation, but the medical community needs to build up trust with a community of users who currently rely more on each other and the Internet for guidance than their primary care physicians. “We need more education. We’re going to need resources to do it,” Dr. O’Connell said. “And we’re going to have to do it.”

Dr. Phillips and Dr. Nagata have no financial disclosures. Mr. Vergel is the owner and founder of Discounted Labs but reported no other financial conflicts. Dr. O’Connor owns Anabolic Doc but has no additional financial disclosures.

A version of this article first appeared on Medscape.com.

Before he attended medical school, Thomas O’Connor, MD, had a not-very-well-kept secret: As a competitive powerlifter, he had used steroids to build strength.

Now an internist and clinical instructor of medicine at the University of Connecticut, Farmington, Dr. O’Connor’s practice focuses on the needs of men taking testosterone and other anabolic steroids – a group he feels is poorly understood and largely neglected by conventional medical care, perceptions borne out by a 2020 study of steroid users he helped conduct.

“They felt discriminated against, they did not feel comfortable working with their physicians, and they felt that the doctors did not know what they were doing,” Dr. O’Connor said in an interview. His patients often express anger and frustration with doctors they had seen previously.
 

Patients turning to home tests

Not surprisingly, then, many users of illegal anabolic-androgenic steroids (AAS) have adopted a DIY approach to monitoring the side effects of the drugs, turning to direct-to-consumer laboratory tests. Clients can order a panel of labs designed to screen for health conditions commonly associated with use of AAS, such as dyslipidemia, renal and hepatic dysfunction, polycythemia, thrombosis, and insulin resistance. The panels also include tests for levels of different hormones.

Sales of direct-to-consumer tests topped $3.6 billion in the United States in 2022 and are predicted to grow. Some of that spending is coming from people, mostly men, using illegally obtained steroids to build muscle. Although published data on the size of the bodybuilder market are unavailable, the Internet is a ready source of relatively inexpensive tests aimed at helping individuals monitor their health.  

While clinicians may have their doubts about allowing patients to pick and choose tests and interpret their results, proponents claim they empower consumers to take control of their health – and save themselves money in the process.

But a test panel designed to help the user monitor the effects of banned substances is a bit unnerving to many clinicians, including Dr. O’Connor.

“People using anabolic steroids should be aware of the health risks associated with such use and that laboratory analysis is an important step toward improving health outcomes,” he said, “I’m all about open education, but not self-diagnosis and treatment.” 

Testosterone and other AAS such as nandrolone, trenbolone, and boldenone are Schedule III controlled substances that have been banned by numerous athletic governing bodies. Yet recreational users can easily obtain them from online international pharmacies without a prescription. Should they be monitoring themselves for side effects?

A basic problem is that few primary care clinicians routinely ask their patients about the use of AAS or feel competent to manage the complications or withdrawal symptoms associated with the agents. And they may have no idea what the average AAS user looks like.

The American College of Sports Medicine updated its statement on the use of AAS in 2021. The statement warned of a growing new segment of users – up to 70% of people who take the drugs do so recreationally in pursuit of a more muscular appearance, rather than competitive athletes seeking enhanced performance.

The ACSM highlighted the syndrome of muscle dysmorphia, also known as “megarexia” or “bigorexia” (think of it as “reverse anorexia”), as a major risk factor for illicit use of AAS.

Stuart Phillips, PhD, professor and director of the department of kinesiology at McMaster University, Hamilton, Ont., coauthored the ACSM guidelines. 

“The prince in Snow White circa 1950s was a guy with nice hair,” said Dr. Phillips, pointing to a change in cultural expectations for the male body. “But then fast forward to the prince or hero in any other Disney movie recently – and the guy is jacked.”

Since the last guidelines were published in 1987, Dr. Phillips has seen some cultural shifts. Testosterone has gone from a banned substance no one talked about to a mainstream medical therapy for men with low androgen levels, as any television viewer of primetime sports can attest. “But the other thing that’s changed,” he added, “is that we’ve seen the proliferation of illicit anabolic steroid use solely for the purpose of aesthetics.”

As an adolescent medicine physician who specializes in eating disorders, Jason Nagata, MD, MSc, sees many young men in his practice who engage in different behaviors to increase their muscle mass – from exercising, consuming high protein diets or taking protein supplements, even injecting AAS.

“A third of teenage boys across the U.S. report they’re trying to gain weight to bulk up and gain muscle,” said Dr. Nagata, an associate professor of pediatrics at the University of California, San Francisco.

In a 2020 study published in JAMA Pediatrics, Dr. Nagata and colleagues found that use of legal performance-enhancing substances in young men aged 18-26 years was associated with a higher odds of using AAS 7 years later (adjusted odds ratio, 3.18; 95% confidence interval, 1.90-5.32). “Some of the legal performance-enhancing substances like the protein powders or creatine may serve as a gateway to use of AAS,” Dr. Nagata said.  

Another important factor is exposure to AAS use on social media, where muscular influencers gain huge followings. Dr. Nagata said most of the research on eating disorders and social media has examined the role of media on weight loss in girls.

“Although there’s less research on the social media impact on boys and men, a few studies have shown links between more Instagram use and muscle dissatisfaction, as well as thinking about using steroids,” he said.

The number of people using AAS is not trivial. In a longitudinal study (led by Nagata) of young U.S. adults surveyed multiple times between 1994 and 2002, a total of 2.7% of 18- to 26-year-old men and 0.4% of women reported using AAS. In a more recent cohort of adolescents in Minnesota aged 14-22 years followed between 2010 and 2018, a total of 2.2% of males and 1% of females initiated AAS use. 

The Endocrine Society has estimated that between 2.9 and 4 million Americans have used an AAS at some point in their lives. Given that use is illegal without a prescription, a limitation of any survey is that participants may not be willing to disclose their AAS habit, leading to an underestimate of the actual number.

Nor are the complications of AAS use negligible. The drugs can have wide-ranging effects on the body, potentially affecting the brain, heart, liver, kidneys, musculoskeletal system, immune system, and reproductive systems. And individuals might unknowingly expose themselves to AAS: A recent literature review found that over a quarter of dietary supplements tested were found to contain undeclared substances that are on the World Anti-Doping Agency’s list of banned agents.
 

Alarming mistrust of MDs

Dr. O’Connor’s study shed some light on why AAS users might resort to surfing the Internet looking for a way to diagnose their own complications from steroid use. The web-based survey of nearly 2,400 men who said they took the drugs found that participants considered physicians to be the worst source of information, ranking them below coaches, online bodybuilding forums and sites, other AAS users, and bodybuilding books or magazines. The majority (56%) did not reveal AAS use to their clinicians. Of those who did, 55% reported feeling discriminated against for the admission.

Dr. O’Connor said physicians receive scant education on the many different drugs and regimens used by bodybuilders and have no idea how to a manage withdrawal syndrome for people trying to get off steroids. He urged the medical community to develop an educational campaign for clinicians, similar to those from public health officials aimed at combating the opioid epidemic: “Let’s educate med students and the residents. Let’s put [steroid use] on our agenda.”
 

Consumer testing evangelist ... or physician nemesis?

Nelson Vergel, BSChE, MBA, is on a mission to make medical lab testing affordable and accessible to everyone. The chemical engineer founded Discounted Labs 8 years ago, offering commonly ordered tests, such as complete blood counts, liver function tests, and cholesterol levels.

Mr. Vergel has advocated for the use of hormones to treat HIV-wasting disease for nearly 40 years, after his own diagnosis of the infection in 1986. After losing 40 pounds, steroids saved his life, he said.

Mr. Vergel said he was shocked to learn about the lack of continuing medical education on AAS for physicians and agreed with Dr. O’Connor that more training is needed for the medical profession. He also recognized that stigma on the part of clinicians is a huge barrier for many AAS users.

“We have to accept the fact that people are using them instead of demonizing them,” Mr. Vergel said. “What I was seeing is that there was so much stigma – and patients would not even talk to their doctors about their use.”

After reviewing Google analytics for his lab’s website and seeing how often “bodybuilder” came up as a search term, he added a panel of labs a year ago that allows AAS users to monitor themselves for adverse events.

Although he doesn’t condone the use of AAS without a medical indication and advises customers to discuss their results with a doctor, “we have to make sure people are reducing their harm or risk,” he said. “That’s really my goal.”

Many health care professionals would disagree with that statement. Dr. Nagata said he was concerned that management of side effects is too complicated. “There are a lot of nuances in the interpretation of these tests.” Arriving at the correct interpretation of the results requires a clinician’s thorough review of each patient’s health history, family history, and mental health history along with lab results. 
 

‘I’m concerned’

In a second article outlining harm-reduction strategies designed to improve care for patients using AAS, Dr. O’Connor and colleagues outlined an approach for talking with patients who are concerned about their health and are seeking guidance from a clinician.

The first step is to work on developing a rapport, and not to demand that patients stop their use of AAS. His recommended opening line is: “I want to be honest with you – I’m concerned.”

The initial interaction is an opportunity to find out why the person uses AAS, what health concerns they have at present, and why they are seeking care. Open-ended questions may reveal concerns that the patient has about fertility or side effects.

Consistent with harm-reduction approaches used for other public health epidemics – such as opioid abuse and blood-borne pathogens among people who inject drugs – follow-up visits can include nonjudgmental discussions about decreasing or stopping their use.

Ultimately, minimizing the harms of AAS use can serve as a bridge to their cessation, but the medical community needs to build up trust with a community of users who currently rely more on each other and the Internet for guidance than their primary care physicians. “We need more education. We’re going to need resources to do it,” Dr. O’Connell said. “And we’re going to have to do it.”

Dr. Phillips and Dr. Nagata have no financial disclosures. Mr. Vergel is the owner and founder of Discounted Labs but reported no other financial conflicts. Dr. O’Connor owns Anabolic Doc but has no additional financial disclosures.

A version of this article first appeared on Medscape.com.

Patient after patient, emergency medicine physicians experience highs and lows, sometimes minutes apart. “It might be another Tuesday for us, but for the patient in that dramatic life moment on that day, it’s everything,” said Charissa Pacella, MD, chief of emergency medicine at UPMC Presbyterian in Pittsburgh.

Emergency department (ED) physicians frequently encounter fatal situations, feel frustration when they can’t save a person, and constantly see patients in distress. How do physicians weather the emotional storm of life in the ED with both their mental health and empathy intact?

Two ED physicians shared how they stay calm, deal with clinical treatments that may not ultimately save the patient, and create sound emotional boundaries.
 

Reserve time for emotions

Dr. Pacella, who has been practicing emergency medicine for 22 years, also serves in a leadership role for Physicians for Physicians, a confidential peer support program at UPMC for doctors struggling with the impact of adverse events and the stress they face. She said it’s essential to know how to compartmentalize and focus on the task at hand, but later revisit emotions from a personal perspective.

“We all separate our cognitive and leadership roles from our emotional response in the moment,” she said. “Everybody is just focused on doing the next right thing. And often it’s not until sometime later when you sit down or go home or maybe even going in for your next shift that it really hits you in a more emotional way.”

If you try to avoid or skip over this part of the process by shoving the emotions down and ignoring them, Dr. Pacella said, you leave out a crucial part of the care process. And over the course of a career, you’ll risk losing empathy and the human connection that most doctors went into medicine for, she told this news organization.
 

Connect with your colleagues

Physicians supporting each other is crucial, said Dr Pacella. And luckily, she added, connection tends to be a strength of the specialty.

“As emergency medicine physicians, we share a lot in common, and part of it is what brought us to choose this specialty in the first place. You picked it because there’s something appealing to you about the unknown. It’s a unique role, a unique environment, and a unique relationship you have with patients and being able to connect with colleagues,” she said.

Lisa Williford, MD, emergency medicine specialist at Texas Health Harris Methodist Hospital in Fort Worth, said her 14-year career has taught her that no matter how focused a medical professional can stay in the moment, emotions are happening at some level.

“During a level 1 trauma, there are a lot of people in the room – trauma surgeons, residents, nurses, x-ray techs, respiratory therapy, anesthesia – and every one of us is having emotions. It’s not realistic to think anyone is avoiding it.”

But beyond simply recognizing a shared experience, it’s important to talk to each other. It’s not just about how you’re feeling, but also what you do to help manage that emotional load.

“I’d say that more of us, especially since COVID, are learning that actually getting a therapist is a good thing, having a life coach is a good thing,” said Dr. Williford. Accepting mental health care and learning how to manage it is also a good thing.
 

Accept unpredictability

You may think you know how a difficult situation will affect you, but that assumption can put you in a vulnerable position. Dr. Pacella said she’s learned that for most physicians, a stress response to a critical incident often has less to do with the type of event and more about who is involved or your past experiences.

“I have reacted in a very emotional way at moments that I would never have expected or predicted,” said Dr. Pacella. “And it’s not always because of some awful event. It’s usually because of some emotional connection or trigger embedded in that encounter.”

For example, she said, you may have had a past case as an emergency physician where the outcome was not favorable, or the patient involved may remind you of yourself or someone you love.

“It might not necessarily be a horrible thing happening to a young, healthy person that triggers someone; it might be a minor problem involving a patient you, for whatever reason, identify with,” she said. “Or you may have had a similar patient where things didn’t go well for them. It’s just highly variable, even for an individual.”

Just as you can’t know what medical issues you’ll face in a day, you can’t predict how you’ll react. Approach each scenario with the knowledge that you may veer off emotional course – and prepare accordingly.
 

Bring mental wellness to the forefront of training

Dr. Williford, who also serves as regional director for ScribeNest, a doctor-operated company that trains medical scribes who are on the path to becoming medical professionals, said she feels strongly about bringing this conversation to the younger generation.

“For me, nobody at the med school level or residency level taught or talked about how to compartmentalize and cope with the traumatic experiences that we saw,” she said. “Only in the last decade have we started teaching our residents and medical students about burnout and resilience.

“I say things like, ‘Hey, we just witnessed an 18-year-old in cardiac arrest. We did CPR for an hour and didn’t get him back. And then you witnessed me tell his mom, who wailed. And then we turned around and treated an ankle sprain. Let’s sit down and talk about how jarring that all is and how nobody else experiences these things.’

“We have this expectation that our physicians know how to move on and connect with each new patient with care and empathy, but we have to tell our future doctors the actual steps we take to be able to do that.”

Seasoned physicians can lead the way for the next generation and turn the tide toward the normalization of talking about these struggles. By making it part of training, it becomes part of a physician’s skill set.

“With a happy, healthy career, we can pay it forward to the next generation and teach them how to be better than we were,” said Dr. Williford.
 

A version of this article appeared on Medscape.com.

Patient after patient, emergency medicine physicians experience highs and lows, sometimes minutes apart. “It might be another Tuesday for us, but for the patient in that dramatic life moment on that day, it’s everything,” said Charissa Pacella, MD, chief of emergency medicine at UPMC Presbyterian in Pittsburgh.

Emergency department (ED) physicians frequently encounter fatal situations, feel frustration when they can’t save a person, and constantly see patients in distress. How do physicians weather the emotional storm of life in the ED with both their mental health and empathy intact?

Two ED physicians shared how they stay calm, deal with clinical treatments that may not ultimately save the patient, and create sound emotional boundaries.
 

Reserve time for emotions

Dr. Pacella, who has been practicing emergency medicine for 22 years, also serves in a leadership role for Physicians for Physicians, a confidential peer support program at UPMC for doctors struggling with the impact of adverse events and the stress they face. She said it’s essential to know how to compartmentalize and focus on the task at hand, but later revisit emotions from a personal perspective.

“We all separate our cognitive and leadership roles from our emotional response in the moment,” she said. “Everybody is just focused on doing the next right thing. And often it’s not until sometime later when you sit down or go home or maybe even going in for your next shift that it really hits you in a more emotional way.”

If you try to avoid or skip over this part of the process by shoving the emotions down and ignoring them, Dr. Pacella said, you leave out a crucial part of the care process. And over the course of a career, you’ll risk losing empathy and the human connection that most doctors went into medicine for, she told this news organization.
 

Connect with your colleagues

Physicians supporting each other is crucial, said Dr Pacella. And luckily, she added, connection tends to be a strength of the specialty.

“As emergency medicine physicians, we share a lot in common, and part of it is what brought us to choose this specialty in the first place. You picked it because there’s something appealing to you about the unknown. It’s a unique role, a unique environment, and a unique relationship you have with patients and being able to connect with colleagues,” she said.

Lisa Williford, MD, emergency medicine specialist at Texas Health Harris Methodist Hospital in Fort Worth, said her 14-year career has taught her that no matter how focused a medical professional can stay in the moment, emotions are happening at some level.

“During a level 1 trauma, there are a lot of people in the room – trauma surgeons, residents, nurses, x-ray techs, respiratory therapy, anesthesia – and every one of us is having emotions. It’s not realistic to think anyone is avoiding it.”

But beyond simply recognizing a shared experience, it’s important to talk to each other. It’s not just about how you’re feeling, but also what you do to help manage that emotional load.

“I’d say that more of us, especially since COVID, are learning that actually getting a therapist is a good thing, having a life coach is a good thing,” said Dr. Williford. Accepting mental health care and learning how to manage it is also a good thing.
 

Accept unpredictability

You may think you know how a difficult situation will affect you, but that assumption can put you in a vulnerable position. Dr. Pacella said she’s learned that for most physicians, a stress response to a critical incident often has less to do with the type of event and more about who is involved or your past experiences.

“I have reacted in a very emotional way at moments that I would never have expected or predicted,” said Dr. Pacella. “And it’s not always because of some awful event. It’s usually because of some emotional connection or trigger embedded in that encounter.”

For example, she said, you may have had a past case as an emergency physician where the outcome was not favorable, or the patient involved may remind you of yourself or someone you love.

“It might not necessarily be a horrible thing happening to a young, healthy person that triggers someone; it might be a minor problem involving a patient you, for whatever reason, identify with,” she said. “Or you may have had a similar patient where things didn’t go well for them. It’s just highly variable, even for an individual.”

Just as you can’t know what medical issues you’ll face in a day, you can’t predict how you’ll react. Approach each scenario with the knowledge that you may veer off emotional course – and prepare accordingly.
 

Bring mental wellness to the forefront of training

Dr. Williford, who also serves as regional director for ScribeNest, a doctor-operated company that trains medical scribes who are on the path to becoming medical professionals, said she feels strongly about bringing this conversation to the younger generation.

“For me, nobody at the med school level or residency level taught or talked about how to compartmentalize and cope with the traumatic experiences that we saw,” she said. “Only in the last decade have we started teaching our residents and medical students about burnout and resilience.

“I say things like, ‘Hey, we just witnessed an 18-year-old in cardiac arrest. We did CPR for an hour and didn’t get him back. And then you witnessed me tell his mom, who wailed. And then we turned around and treated an ankle sprain. Let’s sit down and talk about how jarring that all is and how nobody else experiences these things.’

“We have this expectation that our physicians know how to move on and connect with each new patient with care and empathy, but we have to tell our future doctors the actual steps we take to be able to do that.”

Seasoned physicians can lead the way for the next generation and turn the tide toward the normalization of talking about these struggles. By making it part of training, it becomes part of a physician’s skill set.

“With a happy, healthy career, we can pay it forward to the next generation and teach them how to be better than we were,” said Dr. Williford.
 

A version of this article appeared on Medscape.com.

Patient after patient, emergency medicine physicians experience highs and lows, sometimes minutes apart. “It might be another Tuesday for us, but for the patient in that dramatic life moment on that day, it’s everything,” said Charissa Pacella, MD, chief of emergency medicine at UPMC Presbyterian in Pittsburgh.

Emergency department (ED) physicians frequently encounter fatal situations, feel frustration when they can’t save a person, and constantly see patients in distress. How do physicians weather the emotional storm of life in the ED with both their mental health and empathy intact?

Two ED physicians shared how they stay calm, deal with clinical treatments that may not ultimately save the patient, and create sound emotional boundaries.
 

Reserve time for emotions

Dr. Pacella, who has been practicing emergency medicine for 22 years, also serves in a leadership role for Physicians for Physicians, a confidential peer support program at UPMC for doctors struggling with the impact of adverse events and the stress they face. She said it’s essential to know how to compartmentalize and focus on the task at hand, but later revisit emotions from a personal perspective.

“We all separate our cognitive and leadership roles from our emotional response in the moment,” she said. “Everybody is just focused on doing the next right thing. And often it’s not until sometime later when you sit down or go home or maybe even going in for your next shift that it really hits you in a more emotional way.”

If you try to avoid or skip over this part of the process by shoving the emotions down and ignoring them, Dr. Pacella said, you leave out a crucial part of the care process. And over the course of a career, you’ll risk losing empathy and the human connection that most doctors went into medicine for, she told this news organization.
 

Connect with your colleagues

Physicians supporting each other is crucial, said Dr Pacella. And luckily, she added, connection tends to be a strength of the specialty.

“As emergency medicine physicians, we share a lot in common, and part of it is what brought us to choose this specialty in the first place. You picked it because there’s something appealing to you about the unknown. It’s a unique role, a unique environment, and a unique relationship you have with patients and being able to connect with colleagues,” she said.

Lisa Williford, MD, emergency medicine specialist at Texas Health Harris Methodist Hospital in Fort Worth, said her 14-year career has taught her that no matter how focused a medical professional can stay in the moment, emotions are happening at some level.

“During a level 1 trauma, there are a lot of people in the room – trauma surgeons, residents, nurses, x-ray techs, respiratory therapy, anesthesia – and every one of us is having emotions. It’s not realistic to think anyone is avoiding it.”

But beyond simply recognizing a shared experience, it’s important to talk to each other. It’s not just about how you’re feeling, but also what you do to help manage that emotional load.

“I’d say that more of us, especially since COVID, are learning that actually getting a therapist is a good thing, having a life coach is a good thing,” said Dr. Williford. Accepting mental health care and learning how to manage it is also a good thing.
 

Accept unpredictability

You may think you know how a difficult situation will affect you, but that assumption can put you in a vulnerable position. Dr. Pacella said she’s learned that for most physicians, a stress response to a critical incident often has less to do with the type of event and more about who is involved or your past experiences.

“I have reacted in a very emotional way at moments that I would never have expected or predicted,” said Dr. Pacella. “And it’s not always because of some awful event. It’s usually because of some emotional connection or trigger embedded in that encounter.”

For example, she said, you may have had a past case as an emergency physician where the outcome was not favorable, or the patient involved may remind you of yourself or someone you love.

“It might not necessarily be a horrible thing happening to a young, healthy person that triggers someone; it might be a minor problem involving a patient you, for whatever reason, identify with,” she said. “Or you may have had a similar patient where things didn’t go well for them. It’s just highly variable, even for an individual.”

Just as you can’t know what medical issues you’ll face in a day, you can’t predict how you’ll react. Approach each scenario with the knowledge that you may veer off emotional course – and prepare accordingly.
 

Bring mental wellness to the forefront of training

Dr. Williford, who also serves as regional director for ScribeNest, a doctor-operated company that trains medical scribes who are on the path to becoming medical professionals, said she feels strongly about bringing this conversation to the younger generation.

“For me, nobody at the med school level or residency level taught or talked about how to compartmentalize and cope with the traumatic experiences that we saw,” she said. “Only in the last decade have we started teaching our residents and medical students about burnout and resilience.

“I say things like, ‘Hey, we just witnessed an 18-year-old in cardiac arrest. We did CPR for an hour and didn’t get him back. And then you witnessed me tell his mom, who wailed. And then we turned around and treated an ankle sprain. Let’s sit down and talk about how jarring that all is and how nobody else experiences these things.’

“We have this expectation that our physicians know how to move on and connect with each new patient with care and empathy, but we have to tell our future doctors the actual steps we take to be able to do that.”

Seasoned physicians can lead the way for the next generation and turn the tide toward the normalization of talking about these struggles. By making it part of training, it becomes part of a physician’s skill set.

“With a happy, healthy career, we can pay it forward to the next generation and teach them how to be better than we were,” said Dr. Williford.
 

A version of this article appeared on Medscape.com.

The widening threat of the animal tranquilizer xylazine, otherwise known as tranq, which has been found in illegally manufactured fentanyl, necessitates wider testing, a better understanding of its effects, and more research on treatment options, according to a narrative review published in the Annals of Internal Medicine.

“A lot of doctors and providers are asking about this drug,” said Joseph D’Orazio, MD, an addiction medicine specialist and medical toxicologist at Cooper University Healthcare, Camden, N.J., who led the review.

Xylazine is believed to prolong or intensify the effects of opioids, making it a popular additive to illegally produced opioids, particularly fentanyl, according to the Drug Enforcement Administration. Users end up in a zombie-like state with slowed breathing, and they sometimes develop skin ulcers. Because xylazine is not an opioid, common antidotes such as naloxone are ineffective. The White House has called the fentanyl-xylazine combo an “emerging threat.”

“Xylazine is making the deadliest drug threat our country has ever faced, fentanyl, even deadlier,” said DEA administrator Anne Milgram, in a statement on the agency’s website. “DEA has seized xylazine and fentanyl mixtures in 48 of 50 States. The DEA Laboratory System is reporting that in 2022 approximately 23% of fentanyl powder and 7% of fentanyl pills seized by the DEA contained xylazine.”

Dr. D’Orazio paired clinical experience with available research to provide guidance on the care of patients exposed to xylazine.

He and his team issued a call for more research on the drug’s effects, including more details on dependency and withdrawal.

Testing a patient who may have been exposed to xylazine requires forensic lab capabilities, which makes testing complicated and costly. The review found no evidence of the origin of the drug or why it causes open sores.

The review calls for more education of providers, including primary care physicians, on the treatment and care of patients who have used xylazine and fentanyl. The authors also call for expanding standard urine analysis to test for xylazine and for intensifying surveillance of the drug supply and distribution of xylazine test strips.

The authors of an editorial that accompanied the journal article urged the health care community to get ahead of xylazine before the crisis worsens.

“Not testing for xylazine in current unaffected areas and populations may lead to delays in responding if and when the drug becomes prevalent in the drug supply,” the authors wrote.

Xylazine was detected in 90% of street opioid samples tested in Philadelphia in 2021, and a toxic surveillance study of drug paraphernalia in Maryland found xylazine in 80% of samples tested between 2021 and 2022.

Dr. D’Orazio stressed that although Narcan is ineffective in treating xylazine, because the sedative is almost always mixed with fentanyl or another opiate, the opioid antagonist should still be used in emergencies.

Angelique Campen, MD, an emergency medicine physician at Providence St. Joseph Medical Center, Burbank, Calif., said she has seen an increase in patients entering the emergency department under the influence of what seems like fentanyl or heroin, but standard treatments such as Narcan have a limited effect. These patients remain in a prolonged period of sedation.

Recently, she admitted to her hospital’s intensive care unit a patient suspected of a xylazine overdose who was not responding to treatment.

Dr. Campen said that patients are screened for fentanyl, but because no test is available for xylazine, she presumed xylazine was causing the complication.

“It makes perfect medical sense to me that that’s what was going on,” Dr. Campen, who has worked at St. Joseph’s for 25 years, said. “I’m hoping with physicians being more aware of it that we can have that part of our regular urine drug screen.”

Dr. Campen also said she hopes an antidote is soon developed.

“If we can just keep delivering that message, hopefully, [to] more and more people, it will get through to them,” she said. “Every time you’re taking this, even though you may have taken it a week before and been fine, you never know: The next dose you take may be the lethal dose.”

A review author reports being awarded $1,000 to cover travel cost for Best Overall Abstract at the American Society of Addiction Medicine 2023 Annual Meeting. Another author reports receiving payments for training conducted as part of a NJDMAHS training grant to educate on substance use disorders. Dr. D’Orazio reports a $500 honorarium for a one-time lecture on xylazine at Yale; and a $500 honorarium for speaking one to three times per year on various topics regarding opioid use disorder at the Health Federation of Philadelphia. No other disclosures were reported.

A version of this article first appeared on Medscape.com.

The widening threat of the animal tranquilizer xylazine, otherwise known as tranq, which has been found in illegally manufactured fentanyl, necessitates wider testing, a better understanding of its effects, and more research on treatment options, according to a narrative review published in the Annals of Internal Medicine.

“A lot of doctors and providers are asking about this drug,” said Joseph D’Orazio, MD, an addiction medicine specialist and medical toxicologist at Cooper University Healthcare, Camden, N.J., who led the review.

Xylazine is believed to prolong or intensify the effects of opioids, making it a popular additive to illegally produced opioids, particularly fentanyl, according to the Drug Enforcement Administration. Users end up in a zombie-like state with slowed breathing, and they sometimes develop skin ulcers. Because xylazine is not an opioid, common antidotes such as naloxone are ineffective. The White House has called the fentanyl-xylazine combo an “emerging threat.”

“Xylazine is making the deadliest drug threat our country has ever faced, fentanyl, even deadlier,” said DEA administrator Anne Milgram, in a statement on the agency’s website. “DEA has seized xylazine and fentanyl mixtures in 48 of 50 States. The DEA Laboratory System is reporting that in 2022 approximately 23% of fentanyl powder and 7% of fentanyl pills seized by the DEA contained xylazine.”

Dr. D’Orazio paired clinical experience with available research to provide guidance on the care of patients exposed to xylazine.

He and his team issued a call for more research on the drug’s effects, including more details on dependency and withdrawal.

Testing a patient who may have been exposed to xylazine requires forensic lab capabilities, which makes testing complicated and costly. The review found no evidence of the origin of the drug or why it causes open sores.

The review calls for more education of providers, including primary care physicians, on the treatment and care of patients who have used xylazine and fentanyl. The authors also call for expanding standard urine analysis to test for xylazine and for intensifying surveillance of the drug supply and distribution of xylazine test strips.

The authors of an editorial that accompanied the journal article urged the health care community to get ahead of xylazine before the crisis worsens.

“Not testing for xylazine in current unaffected areas and populations may lead to delays in responding if and when the drug becomes prevalent in the drug supply,” the authors wrote.

Xylazine was detected in 90% of street opioid samples tested in Philadelphia in 2021, and a toxic surveillance study of drug paraphernalia in Maryland found xylazine in 80% of samples tested between 2021 and 2022.

Dr. D’Orazio stressed that although Narcan is ineffective in treating xylazine, because the sedative is almost always mixed with fentanyl or another opiate, the opioid antagonist should still be used in emergencies.

Angelique Campen, MD, an emergency medicine physician at Providence St. Joseph Medical Center, Burbank, Calif., said she has seen an increase in patients entering the emergency department under the influence of what seems like fentanyl or heroin, but standard treatments such as Narcan have a limited effect. These patients remain in a prolonged period of sedation.

Recently, she admitted to her hospital’s intensive care unit a patient suspected of a xylazine overdose who was not responding to treatment.

Dr. Campen said that patients are screened for fentanyl, but because no test is available for xylazine, she presumed xylazine was causing the complication.

“It makes perfect medical sense to me that that’s what was going on,” Dr. Campen, who has worked at St. Joseph’s for 25 years, said. “I’m hoping with physicians being more aware of it that we can have that part of our regular urine drug screen.”

Dr. Campen also said she hopes an antidote is soon developed.

“If we can just keep delivering that message, hopefully, [to] more and more people, it will get through to them,” she said. “Every time you’re taking this, even though you may have taken it a week before and been fine, you never know: The next dose you take may be the lethal dose.”

A review author reports being awarded $1,000 to cover travel cost for Best Overall Abstract at the American Society of Addiction Medicine 2023 Annual Meeting. Another author reports receiving payments for training conducted as part of a NJDMAHS training grant to educate on substance use disorders. Dr. D’Orazio reports a $500 honorarium for a one-time lecture on xylazine at Yale; and a $500 honorarium for speaking one to three times per year on various topics regarding opioid use disorder at the Health Federation of Philadelphia. No other disclosures were reported.

A version of this article first appeared on Medscape.com.

The widening threat of the animal tranquilizer xylazine, otherwise known as tranq, which has been found in illegally manufactured fentanyl, necessitates wider testing, a better understanding of its effects, and more research on treatment options, according to a narrative review published in the Annals of Internal Medicine.

“A lot of doctors and providers are asking about this drug,” said Joseph D’Orazio, MD, an addiction medicine specialist and medical toxicologist at Cooper University Healthcare, Camden, N.J., who led the review.

Xylazine is believed to prolong or intensify the effects of opioids, making it a popular additive to illegally produced opioids, particularly fentanyl, according to the Drug Enforcement Administration. Users end up in a zombie-like state with slowed breathing, and they sometimes develop skin ulcers. Because xylazine is not an opioid, common antidotes such as naloxone are ineffective. The White House has called the fentanyl-xylazine combo an “emerging threat.”

“Xylazine is making the deadliest drug threat our country has ever faced, fentanyl, even deadlier,” said DEA administrator Anne Milgram, in a statement on the agency’s website. “DEA has seized xylazine and fentanyl mixtures in 48 of 50 States. The DEA Laboratory System is reporting that in 2022 approximately 23% of fentanyl powder and 7% of fentanyl pills seized by the DEA contained xylazine.”

Dr. D’Orazio paired clinical experience with available research to provide guidance on the care of patients exposed to xylazine.

He and his team issued a call for more research on the drug’s effects, including more details on dependency and withdrawal.

Testing a patient who may have been exposed to xylazine requires forensic lab capabilities, which makes testing complicated and costly. The review found no evidence of the origin of the drug or why it causes open sores.

The review calls for more education of providers, including primary care physicians, on the treatment and care of patients who have used xylazine and fentanyl. The authors also call for expanding standard urine analysis to test for xylazine and for intensifying surveillance of the drug supply and distribution of xylazine test strips.

The authors of an editorial that accompanied the journal article urged the health care community to get ahead of xylazine before the crisis worsens.

“Not testing for xylazine in current unaffected areas and populations may lead to delays in responding if and when the drug becomes prevalent in the drug supply,” the authors wrote.

Xylazine was detected in 90% of street opioid samples tested in Philadelphia in 2021, and a toxic surveillance study of drug paraphernalia in Maryland found xylazine in 80% of samples tested between 2021 and 2022.

Dr. D’Orazio stressed that although Narcan is ineffective in treating xylazine, because the sedative is almost always mixed with fentanyl or another opiate, the opioid antagonist should still be used in emergencies.

Angelique Campen, MD, an emergency medicine physician at Providence St. Joseph Medical Center, Burbank, Calif., said she has seen an increase in patients entering the emergency department under the influence of what seems like fentanyl or heroin, but standard treatments such as Narcan have a limited effect. These patients remain in a prolonged period of sedation.

Recently, she admitted to her hospital’s intensive care unit a patient suspected of a xylazine overdose who was not responding to treatment.

Dr. Campen said that patients are screened for fentanyl, but because no test is available for xylazine, she presumed xylazine was causing the complication.

“It makes perfect medical sense to me that that’s what was going on,” Dr. Campen, who has worked at St. Joseph’s for 25 years, said. “I’m hoping with physicians being more aware of it that we can have that part of our regular urine drug screen.”

Dr. Campen also said she hopes an antidote is soon developed.

“If we can just keep delivering that message, hopefully, [to] more and more people, it will get through to them,” she said. “Every time you’re taking this, even though you may have taken it a week before and been fine, you never know: The next dose you take may be the lethal dose.”

A review author reports being awarded $1,000 to cover travel cost for Best Overall Abstract at the American Society of Addiction Medicine 2023 Annual Meeting. Another author reports receiving payments for training conducted as part of a NJDMAHS training grant to educate on substance use disorders. Dr. D’Orazio reports a $500 honorarium for a one-time lecture on xylazine at Yale; and a $500 honorarium for speaking one to three times per year on various topics regarding opioid use disorder at the Health Federation of Philadelphia. No other disclosures were reported.

A version of this article first appeared on Medscape.com.

With the emergence of pirfenidone and nintedanib over the past decade or so, pulmonologists now have at their disposal two breakthrough antifibrotic agents for the treatment of idiopathic pulmonary fibrosis.

Artfoliophoto/Thinkstock

But these two drugs have a number of shortcomings that a host of investigative agents are aiming to address. For one, while pirfenidone and nintedanib have been shown to slow disease progression and improve symptoms, they don’t stop or reverse the disease. Also, a large number of patients with IPF don’t tolerate these drugs well. And, their high cost is a barrier for many patients.

Joyce Lee, MD

“There are no curative therapies that improve lung function or improve symptoms, so there remains a very large unmet need in terms of therapies or interventions that have better efficacy, better long-term tolerability, and that improve symptoms and quality of life for our patients with IPF disease,” said Joyce Lee, MD, associate professor of medicine–pulmonary at the University of Colorado at Denver, Aurora, and senior medical adviser for research and health care quality for the Pulmonary Fibrosis Foundation.

The National Institutes of Health estimates that more than 30,000 new cases of IPF are diagnosed in the United States annually, and as many as 3 million people have the disease worldwide. The 5-year survival rate is less than 40% after diagnosis. Bloomberg News reported that more than 80 pharmaceutical companies are working on IPF treatments. iHealthcareAnalyst estimates the global market for IPF will reach $10.1 billion by 2029 thanks to rapidly increasing prevalence and incidence with age, premium-priced drugs, and rapid approval of new treatments.
 

The perils of phase 3 studies

A search on ClinicalTrials.gov turned up 89 investigative IPF treatments in human trials. However, the search for alternatives can be perilous. “In the field, we have gotten used to promising phase 2 studies that failed in the phase 3 stage of development,” Dr. Lee said. “I don’t hold my breath these days just in terms of trying to predict whether or not the efficacy will be present in the phase 3 clinical trial.”

Three notable phase 3 flops include the ISABELA 1 and 2 trials of the autotaxin inhibitor ziritaxestat, which failed to meet their primary endpoint and were halted early (JAMA. 2023;329:1567-78). The phase 3 ZEPHYRUS-1 trial failed to show any benefit of pamrevlumab to improve percent predicted force vital capacity (ppFVC) at week 48, causing discontinuation of a second phase 3 trial. The phase 3 STARSCAPE-OLE study of intravenous recombinant human pentraxin-2 was terminated earlier this year when the sponsor, Hoffmann-LaRoche, decided it was unable to meet its primary objective (NCT04594707).

In the meantime, these six other phase 3 programs in IPF are still in the field:

Anlotinib. A phase 2 and 3 trial in China is evaluating 1-year outcomes of once-daily oral anlotinib for treatment of IPF/progressive fibrosis-interstitial lung disease (PF-ILDS) (NCT05828953). Anlotinib is a tyrosine kinase inhibitor (TKI) that targets four factors: vascular endothelial growth factor receptor (VEGR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. It’s approved in China as a third-line therapy for non–small cell lung cancer (NSCLC).

BI 101550. Enrollment in the FIBRONEER-IPF trial commenced last fall (NCT05321069), with completion scheduled for late next year. BI 1015550 is an oral phosphodiesterase 4B (PDE4B) inhibitor. FIBRONEER-ILD is a separate phase 3 trial in fibrosing idiopathic lung disease (NCT05321082). In both trials, the primary endpoint is the absolute change from baseline in FVC at week 52.

BMS-986278. Results of a phase 2 trial showed that twice-daily treatment with oral BMS-986278 60 mg over 26 weeks reduced the rate of decline in  ppFVC by 69% vs. placebo. The phase 3 ALOFT trial has been approved but hasn’t yet started recruiting patients (NCT06003426). BMS-986278 is a lysophosphatidic acid receptor 1 (LPA1) antagonist.

Lanxoprazole. Commonly used to treat and prevent gastrointestinal problems like stomach ulcers and esophagitis, this oral proton pump inhibitor (PPI) is the focus of a trial in the United Kingdom evaluating if PPIs can slow the progression of IPF (NCT04965298).

N-acetylcysteine (NAC). The PRECISIONS trial is evaluating the effect of NAC plus standard-of-care treatment in IPF patients who have the TOLLIP rs3750910 TT genotype (NCT04300920). Participants receive 600 mg NAC orally or matched placebo three times daily for 24 months. Trial completion is scheduled for 2025.

Treprostinil. Already approved to treat pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease, inhaled Treprostinil is the subject of the TETON 1 and 2 trials evaluating its impact on ppFVC after 52 weeks of treatment (NCT04708782, NCT05255991).
 

Phase 2 candidates

The primary endpoint in most of the phase 2 trials is change in ppFVC capacity from baseline to week 24. The following investigative therapies are in phase 2 trials:

Bexotegrast (PLN-74809), an oral, small molecule, dual-selective inhibitor of alphav/beta6 and alphav/beta1  (NCT04396756).

BBT-877, described as a potent autotaxin (ATX) inhibitor, demonstrated its ability to inhibit lysophosphatidic acid (LPA) production by as much as 90 percent (NCT05483907).

CC-90001, an oral, once-daily c-Jun N-terminal kinases (JNK) inhibitor. JNKs have been implicated in the underlying mechanisms of fibrosis, including epithelial cell death, inflammation and polarization of profibrotic macrophages, fibroblast activation, and collagen production (NCT03142191).

C21 targets the underlying fibrosis in IPF by stimulating the protective arm of the renin-angiotensin system. It also has an upstream effect by promoting alveolar repair by which it can reduce fibrosis formation, stabilize disease, and increase lung capacity (NCT04533022).

CSL312 (garadacimab) is a humanized anti-FXIIa monoclonal antibody administrated intravenously (NCT05130970).

Cudetaxestat, a noncompetitive autotaxin inhibitor (NCT05373914).

Bersiposocin/DWN12088, an inhibitor of prolyl-tRNA synthetase 1 (PARS1), which is suspected to control the pathologic accumulation of collagen containing high amounts of proline in fibrotic diseases (NCT05389215).

ENV-101, a small-molecule inhibitor of the Hedgehog (Hh) signaling pathway, which plays a key role in IPF. This agent was originally developed to target Hh-driven cancers (NCT04968574).

GKT137831 (setanaxib) inhibits nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) isoforms. (NCT03865927).

HZN-825, a lysophosphatidic acid receptor 1 (LPAR1) antagonist. (NCT05032066)

Ifetroban, a potent and selective thromboxane-prostanoid receptor (TPr) antagonist, which exhibits a high affinity for TPr on platelets, vascular and airway smooth muscle, and fibroblasts, and lacks agonistic activity (NCT05571059).

INS018_055, a small-molecule, oral antifibrotic candidate notable for being the first entirely AI-generated drug to enter phase 2 trials. Trial enrollment started in October (NCT05975983, NCT05983920)

Jaktinib dihydrochloride monohydrate, an oral JAK1, JAK2, and JAK3 inhibitor (NCT04312594).

Leramistat, an anti–tumor necrosis factor (TNF) agent (NCT05951296).

LTP001, an oral, selectively deuterated form of pirfenidone designed to retain the antifibrotic and anti-inflammatory activity of pirfenidone with a differentiated pharmacokinetic profile (NCT05497284, NCT05321420).

ME-015 (suplatast tosilate) aims to stabilize ion channels in the neuronal endings in the lungs that mediate IPF-related cough (NCT05983471).

Nalbuphine, a small-molecule, dual-mechanism treatment for chronic cough in IPF. It acts as both a mu opioid receptor antagonist and a kappa opioid receptor agonist (NCT05964335). The CANAL trial, complete last year, is evaluating an extended-release formulation (NCT04030026).

NP-120 (ifenprodil), a small-molecule N-methyl-D-aspartate (NMDA) receptor antagonist, specifically targets the NMDA-type subunit 2B (GluN2B) (NCT04318704).

Orvepitant, a selective antagonist for the NK₁ receptor, is being evaluated to treat IPF-related cough (NCT05815089).

RXC007 (zelasudil), a Rho-associated coiled-coil–containing protein kinase 2 (ROCK2) selective inhibitor, was granted FDA orphan drug designation in August 2023 (NCT05570058).

Saracatinib, a selective Src kinase inhibitor originally developed for oncological indications (NCT04598919).

SHR-1906, an intravenous treatment, inhibits binding of a target protein to a variety of cytokines and growth factors, affects downstream signaling pathways, and reduces cell proliferation and migration (NCT05722964).

TTI-101, an oral, small-molecule inhibitor of signal transducer and activator of transcription (STAT3), which has been found to accumulate in the lungs of IPF patients (NCT05671835).

VAY736 (lanalumab), a BAFF-R inhibitor (NCT03287414).

Vixarelimab, a human monoclonal oncastatin M receptor beta antibody (NCT05785624).

Some investigative programs, however, didn’t make it out of phase 2. The trial evaluating inhaled GB0139, a selective functional antagonist of G-protein–coupled receptor 84, which plays a key role in fibrosis, failed to meet its primary endpoint (NCT03832946). Likewise, oral GLPG1205 failed to show a significant difference in FVC decline vs. placebo (NCT03725852). The program to develop SAR156597, also known as romilkimab, was halted (NCT02345070). ND-L02-s0201n, an siRNA oligonucleotide drug designed to inhibit heat shock protein 47 (HSP47), which regulates collagen synthesis and secretion that causes fibrosis, didn’t show the expected efficacy (NCT03538301).
 

Phase 1 trials

No fewer than 27 phase 1 trials are evaluating investigative treatments for IPF, many in the early phase or not yet recruiting. According to GlobalData, phase 1 drugs for IPF have a 66% chance of moving onto phase 2. Among the advanced phase 1 trials that have gained corporate backing are:

9MW3811, an anti–interleukin-11 monoclonal antibody IV injection (NCT05912049).

ANG-3070, an oral tyrosine kinase inhibitor targeting platelet-derived growth factor (PDGFR) alpha and beta (NCT05387785).

C106, an angiotensin II type 2 receptor agonist (NCT05427253).

HuL001, which targets alpha-enolase (NCT04540770).

LTI-03, a Caveolin-1 (Cav1)-related peptide designed to restore Cav1 expression in lung tissue (NCT05954988).

ORIN1001, a first-in-class small molecule that selectively blocks the inositol requiring enzyme 1alphase (IRE1) RNAse and blocks X-box binding protein 1 (XBP1) activation (NCT04643769).

PRS-220 is an orally inhaled anticalin protein targeting connective tissue growth factor (CTGF) (NTC05473533).

TRK-250, a single-strand, long-chain nucleic acid that selectively suppresses expression of transforming growth factor-beta 1 (TGF-beta1) protein (NCT03727802).

“While we have therapies that we’re able to give patients, we need to do more and we need to do better,” Dr. Lee said. “We’re all hopeful the next phase 3 clinical trial will be something that will help change the treatment paradigm for our patients. We’re very patient, and hopefully those that are interested in improving this treatment landscape will continue to persist.”

Dr. Lee disclosed financial relationships with Boehringer Ingelheim, Pliant Therapeutics, Blade Therapeutics, United Therapeutics, Eleven P15. and Avalyn Pharma.

With the emergence of pirfenidone and nintedanib over the past decade or so, pulmonologists now have at their disposal two breakthrough antifibrotic agents for the treatment of idiopathic pulmonary fibrosis.

Artfoliophoto/Thinkstock

But these two drugs have a number of shortcomings that a host of investigative agents are aiming to address. For one, while pirfenidone and nintedanib have been shown to slow disease progression and improve symptoms, they don’t stop or reverse the disease. Also, a large number of patients with IPF don’t tolerate these drugs well. And, their high cost is a barrier for many patients.

Joyce Lee, MD

“There are no curative therapies that improve lung function or improve symptoms, so there remains a very large unmet need in terms of therapies or interventions that have better efficacy, better long-term tolerability, and that improve symptoms and quality of life for our patients with IPF disease,” said Joyce Lee, MD, associate professor of medicine–pulmonary at the University of Colorado at Denver, Aurora, and senior medical adviser for research and health care quality for the Pulmonary Fibrosis Foundation.

The National Institutes of Health estimates that more than 30,000 new cases of IPF are diagnosed in the United States annually, and as many as 3 million people have the disease worldwide. The 5-year survival rate is less than 40% after diagnosis. Bloomberg News reported that more than 80 pharmaceutical companies are working on IPF treatments. iHealthcareAnalyst estimates the global market for IPF will reach $10.1 billion by 2029 thanks to rapidly increasing prevalence and incidence with age, premium-priced drugs, and rapid approval of new treatments.
 

The perils of phase 3 studies

A search on ClinicalTrials.gov turned up 89 investigative IPF treatments in human trials. However, the search for alternatives can be perilous. “In the field, we have gotten used to promising phase 2 studies that failed in the phase 3 stage of development,” Dr. Lee said. “I don’t hold my breath these days just in terms of trying to predict whether or not the efficacy will be present in the phase 3 clinical trial.”

Three notable phase 3 flops include the ISABELA 1 and 2 trials of the autotaxin inhibitor ziritaxestat, which failed to meet their primary endpoint and were halted early (JAMA. 2023;329:1567-78). The phase 3 ZEPHYRUS-1 trial failed to show any benefit of pamrevlumab to improve percent predicted force vital capacity (ppFVC) at week 48, causing discontinuation of a second phase 3 trial. The phase 3 STARSCAPE-OLE study of intravenous recombinant human pentraxin-2 was terminated earlier this year when the sponsor, Hoffmann-LaRoche, decided it was unable to meet its primary objective (NCT04594707).

In the meantime, these six other phase 3 programs in IPF are still in the field:

Anlotinib. A phase 2 and 3 trial in China is evaluating 1-year outcomes of once-daily oral anlotinib for treatment of IPF/progressive fibrosis-interstitial lung disease (PF-ILDS) (NCT05828953). Anlotinib is a tyrosine kinase inhibitor (TKI) that targets four factors: vascular endothelial growth factor receptor (VEGR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. It’s approved in China as a third-line therapy for non–small cell lung cancer (NSCLC).

BI 101550. Enrollment in the FIBRONEER-IPF trial commenced last fall (NCT05321069), with completion scheduled for late next year. BI 1015550 is an oral phosphodiesterase 4B (PDE4B) inhibitor. FIBRONEER-ILD is a separate phase 3 trial in fibrosing idiopathic lung disease (NCT05321082). In both trials, the primary endpoint is the absolute change from baseline in FVC at week 52.

BMS-986278. Results of a phase 2 trial showed that twice-daily treatment with oral BMS-986278 60 mg over 26 weeks reduced the rate of decline in  ppFVC by 69% vs. placebo. The phase 3 ALOFT trial has been approved but hasn’t yet started recruiting patients (NCT06003426). BMS-986278 is a lysophosphatidic acid receptor 1 (LPA1) antagonist.

Lanxoprazole. Commonly used to treat and prevent gastrointestinal problems like stomach ulcers and esophagitis, this oral proton pump inhibitor (PPI) is the focus of a trial in the United Kingdom evaluating if PPIs can slow the progression of IPF (NCT04965298).

N-acetylcysteine (NAC). The PRECISIONS trial is evaluating the effect of NAC plus standard-of-care treatment in IPF patients who have the TOLLIP rs3750910 TT genotype (NCT04300920). Participants receive 600 mg NAC orally or matched placebo three times daily for 24 months. Trial completion is scheduled for 2025.

Treprostinil. Already approved to treat pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease, inhaled Treprostinil is the subject of the TETON 1 and 2 trials evaluating its impact on ppFVC after 52 weeks of treatment (NCT04708782, NCT05255991).
 

Phase 2 candidates

The primary endpoint in most of the phase 2 trials is change in ppFVC capacity from baseline to week 24. The following investigative therapies are in phase 2 trials:

Bexotegrast (PLN-74809), an oral, small molecule, dual-selective inhibitor of alphav/beta6 and alphav/beta1  (NCT04396756).

BBT-877, described as a potent autotaxin (ATX) inhibitor, demonstrated its ability to inhibit lysophosphatidic acid (LPA) production by as much as 90 percent (NCT05483907).

CC-90001, an oral, once-daily c-Jun N-terminal kinases (JNK) inhibitor. JNKs have been implicated in the underlying mechanisms of fibrosis, including epithelial cell death, inflammation and polarization of profibrotic macrophages, fibroblast activation, and collagen production (NCT03142191).

C21 targets the underlying fibrosis in IPF by stimulating the protective arm of the renin-angiotensin system. It also has an upstream effect by promoting alveolar repair by which it can reduce fibrosis formation, stabilize disease, and increase lung capacity (NCT04533022).

CSL312 (garadacimab) is a humanized anti-FXIIa monoclonal antibody administrated intravenously (NCT05130970).

Cudetaxestat, a noncompetitive autotaxin inhibitor (NCT05373914).

Bersiposocin/DWN12088, an inhibitor of prolyl-tRNA synthetase 1 (PARS1), which is suspected to control the pathologic accumulation of collagen containing high amounts of proline in fibrotic diseases (NCT05389215).

ENV-101, a small-molecule inhibitor of the Hedgehog (Hh) signaling pathway, which plays a key role in IPF. This agent was originally developed to target Hh-driven cancers (NCT04968574).

GKT137831 (setanaxib) inhibits nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) isoforms. (NCT03865927).

HZN-825, a lysophosphatidic acid receptor 1 (LPAR1) antagonist. (NCT05032066)

Ifetroban, a potent and selective thromboxane-prostanoid receptor (TPr) antagonist, which exhibits a high affinity for TPr on platelets, vascular and airway smooth muscle, and fibroblasts, and lacks agonistic activity (NCT05571059).

INS018_055, a small-molecule, oral antifibrotic candidate notable for being the first entirely AI-generated drug to enter phase 2 trials. Trial enrollment started in October (NCT05975983, NCT05983920)

Jaktinib dihydrochloride monohydrate, an oral JAK1, JAK2, and JAK3 inhibitor (NCT04312594).

Leramistat, an anti–tumor necrosis factor (TNF) agent (NCT05951296).

LTP001, an oral, selectively deuterated form of pirfenidone designed to retain the antifibrotic and anti-inflammatory activity of pirfenidone with a differentiated pharmacokinetic profile (NCT05497284, NCT05321420).

ME-015 (suplatast tosilate) aims to stabilize ion channels in the neuronal endings in the lungs that mediate IPF-related cough (NCT05983471).

Nalbuphine, a small-molecule, dual-mechanism treatment for chronic cough in IPF. It acts as both a mu opioid receptor antagonist and a kappa opioid receptor agonist (NCT05964335). The CANAL trial, complete last year, is evaluating an extended-release formulation (NCT04030026).

NP-120 (ifenprodil), a small-molecule N-methyl-D-aspartate (NMDA) receptor antagonist, specifically targets the NMDA-type subunit 2B (GluN2B) (NCT04318704).

Orvepitant, a selective antagonist for the NK₁ receptor, is being evaluated to treat IPF-related cough (NCT05815089).

RXC007 (zelasudil), a Rho-associated coiled-coil–containing protein kinase 2 (ROCK2) selective inhibitor, was granted FDA orphan drug designation in August 2023 (NCT05570058).

Saracatinib, a selective Src kinase inhibitor originally developed for oncological indications (NCT04598919).

SHR-1906, an intravenous treatment, inhibits binding of a target protein to a variety of cytokines and growth factors, affects downstream signaling pathways, and reduces cell proliferation and migration (NCT05722964).

TTI-101, an oral, small-molecule inhibitor of signal transducer and activator of transcription (STAT3), which has been found to accumulate in the lungs of IPF patients (NCT05671835).

VAY736 (lanalumab), a BAFF-R inhibitor (NCT03287414).

Vixarelimab, a human monoclonal oncastatin M receptor beta antibody (NCT05785624).

Some investigative programs, however, didn’t make it out of phase 2. The trial evaluating inhaled GB0139, a selective functional antagonist of G-protein–coupled receptor 84, which plays a key role in fibrosis, failed to meet its primary endpoint (NCT03832946). Likewise, oral GLPG1205 failed to show a significant difference in FVC decline vs. placebo (NCT03725852). The program to develop SAR156597, also known as romilkimab, was halted (NCT02345070). ND-L02-s0201n, an siRNA oligonucleotide drug designed to inhibit heat shock protein 47 (HSP47), which regulates collagen synthesis and secretion that causes fibrosis, didn’t show the expected efficacy (NCT03538301).
 

Phase 1 trials

No fewer than 27 phase 1 trials are evaluating investigative treatments for IPF, many in the early phase or not yet recruiting. According to GlobalData, phase 1 drugs for IPF have a 66% chance of moving onto phase 2. Among the advanced phase 1 trials that have gained corporate backing are:

9MW3811, an anti–interleukin-11 monoclonal antibody IV injection (NCT05912049).

ANG-3070, an oral tyrosine kinase inhibitor targeting platelet-derived growth factor (PDGFR) alpha and beta (NCT05387785).

C106, an angiotensin II type 2 receptor agonist (NCT05427253).

HuL001, which targets alpha-enolase (NCT04540770).

LTI-03, a Caveolin-1 (Cav1)-related peptide designed to restore Cav1 expression in lung tissue (NCT05954988).

ORIN1001, a first-in-class small molecule that selectively blocks the inositol requiring enzyme 1alphase (IRE1) RNAse and blocks X-box binding protein 1 (XBP1) activation (NCT04643769).

PRS-220 is an orally inhaled anticalin protein targeting connective tissue growth factor (CTGF) (NTC05473533).

TRK-250, a single-strand, long-chain nucleic acid that selectively suppresses expression of transforming growth factor-beta 1 (TGF-beta1) protein (NCT03727802).

“While we have therapies that we’re able to give patients, we need to do more and we need to do better,” Dr. Lee said. “We’re all hopeful the next phase 3 clinical trial will be something that will help change the treatment paradigm for our patients. We’re very patient, and hopefully those that are interested in improving this treatment landscape will continue to persist.”

Dr. Lee disclosed financial relationships with Boehringer Ingelheim, Pliant Therapeutics, Blade Therapeutics, United Therapeutics, Eleven P15. and Avalyn Pharma.

With the emergence of pirfenidone and nintedanib over the past decade or so, pulmonologists now have at their disposal two breakthrough antifibrotic agents for the treatment of idiopathic pulmonary fibrosis.

Artfoliophoto/Thinkstock

But these two drugs have a number of shortcomings that a host of investigative agents are aiming to address. For one, while pirfenidone and nintedanib have been shown to slow disease progression and improve symptoms, they don’t stop or reverse the disease. Also, a large number of patients with IPF don’t tolerate these drugs well. And, their high cost is a barrier for many patients.

Joyce Lee, MD

“There are no curative therapies that improve lung function or improve symptoms, so there remains a very large unmet need in terms of therapies or interventions that have better efficacy, better long-term tolerability, and that improve symptoms and quality of life for our patients with IPF disease,” said Joyce Lee, MD, associate professor of medicine–pulmonary at the University of Colorado at Denver, Aurora, and senior medical adviser for research and health care quality for the Pulmonary Fibrosis Foundation.

The National Institutes of Health estimates that more than 30,000 new cases of IPF are diagnosed in the United States annually, and as many as 3 million people have the disease worldwide. The 5-year survival rate is less than 40% after diagnosis. Bloomberg News reported that more than 80 pharmaceutical companies are working on IPF treatments. iHealthcareAnalyst estimates the global market for IPF will reach $10.1 billion by 2029 thanks to rapidly increasing prevalence and incidence with age, premium-priced drugs, and rapid approval of new treatments.
 

The perils of phase 3 studies

A search on ClinicalTrials.gov turned up 89 investigative IPF treatments in human trials. However, the search for alternatives can be perilous. “In the field, we have gotten used to promising phase 2 studies that failed in the phase 3 stage of development,” Dr. Lee said. “I don’t hold my breath these days just in terms of trying to predict whether or not the efficacy will be present in the phase 3 clinical trial.”

Three notable phase 3 flops include the ISABELA 1 and 2 trials of the autotaxin inhibitor ziritaxestat, which failed to meet their primary endpoint and were halted early (JAMA. 2023;329:1567-78). The phase 3 ZEPHYRUS-1 trial failed to show any benefit of pamrevlumab to improve percent predicted force vital capacity (ppFVC) at week 48, causing discontinuation of a second phase 3 trial. The phase 3 STARSCAPE-OLE study of intravenous recombinant human pentraxin-2 was terminated earlier this year when the sponsor, Hoffmann-LaRoche, decided it was unable to meet its primary objective (NCT04594707).

In the meantime, these six other phase 3 programs in IPF are still in the field:

Anlotinib. A phase 2 and 3 trial in China is evaluating 1-year outcomes of once-daily oral anlotinib for treatment of IPF/progressive fibrosis-interstitial lung disease (PF-ILDS) (NCT05828953). Anlotinib is a tyrosine kinase inhibitor (TKI) that targets four factors: vascular endothelial growth factor receptor (VEGR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. It’s approved in China as a third-line therapy for non–small cell lung cancer (NSCLC).

BI 101550. Enrollment in the FIBRONEER-IPF trial commenced last fall (NCT05321069), with completion scheduled for late next year. BI 1015550 is an oral phosphodiesterase 4B (PDE4B) inhibitor. FIBRONEER-ILD is a separate phase 3 trial in fibrosing idiopathic lung disease (NCT05321082). In both trials, the primary endpoint is the absolute change from baseline in FVC at week 52.

BMS-986278. Results of a phase 2 trial showed that twice-daily treatment with oral BMS-986278 60 mg over 26 weeks reduced the rate of decline in  ppFVC by 69% vs. placebo. The phase 3 ALOFT trial has been approved but hasn’t yet started recruiting patients (NCT06003426). BMS-986278 is a lysophosphatidic acid receptor 1 (LPA1) antagonist.

Lanxoprazole. Commonly used to treat and prevent gastrointestinal problems like stomach ulcers and esophagitis, this oral proton pump inhibitor (PPI) is the focus of a trial in the United Kingdom evaluating if PPIs can slow the progression of IPF (NCT04965298).

N-acetylcysteine (NAC). The PRECISIONS trial is evaluating the effect of NAC plus standard-of-care treatment in IPF patients who have the TOLLIP rs3750910 TT genotype (NCT04300920). Participants receive 600 mg NAC orally or matched placebo three times daily for 24 months. Trial completion is scheduled for 2025.

Treprostinil. Already approved to treat pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease, inhaled Treprostinil is the subject of the TETON 1 and 2 trials evaluating its impact on ppFVC after 52 weeks of treatment (NCT04708782, NCT05255991).
 

Phase 2 candidates

The primary endpoint in most of the phase 2 trials is change in ppFVC capacity from baseline to week 24. The following investigative therapies are in phase 2 trials:

Bexotegrast (PLN-74809), an oral, small molecule, dual-selective inhibitor of alphav/beta6 and alphav/beta1  (NCT04396756).

BBT-877, described as a potent autotaxin (ATX) inhibitor, demonstrated its ability to inhibit lysophosphatidic acid (LPA) production by as much as 90 percent (NCT05483907).

CC-90001, an oral, once-daily c-Jun N-terminal kinases (JNK) inhibitor. JNKs have been implicated in the underlying mechanisms of fibrosis, including epithelial cell death, inflammation and polarization of profibrotic macrophages, fibroblast activation, and collagen production (NCT03142191).

C21 targets the underlying fibrosis in IPF by stimulating the protective arm of the renin-angiotensin system. It also has an upstream effect by promoting alveolar repair by which it can reduce fibrosis formation, stabilize disease, and increase lung capacity (NCT04533022).

CSL312 (garadacimab) is a humanized anti-FXIIa monoclonal antibody administrated intravenously (NCT05130970).

Cudetaxestat, a noncompetitive autotaxin inhibitor (NCT05373914).

Bersiposocin/DWN12088, an inhibitor of prolyl-tRNA synthetase 1 (PARS1), which is suspected to control the pathologic accumulation of collagen containing high amounts of proline in fibrotic diseases (NCT05389215).

ENV-101, a small-molecule inhibitor of the Hedgehog (Hh) signaling pathway, which plays a key role in IPF. This agent was originally developed to target Hh-driven cancers (NCT04968574).

GKT137831 (setanaxib) inhibits nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) isoforms. (NCT03865927).

HZN-825, a lysophosphatidic acid receptor 1 (LPAR1) antagonist. (NCT05032066)

Ifetroban, a potent and selective thromboxane-prostanoid receptor (TPr) antagonist, which exhibits a high affinity for TPr on platelets, vascular and airway smooth muscle, and fibroblasts, and lacks agonistic activity (NCT05571059).

INS018_055, a small-molecule, oral antifibrotic candidate notable for being the first entirely AI-generated drug to enter phase 2 trials. Trial enrollment started in October (NCT05975983, NCT05983920)

Jaktinib dihydrochloride monohydrate, an oral JAK1, JAK2, and JAK3 inhibitor (NCT04312594).

Leramistat, an anti–tumor necrosis factor (TNF) agent (NCT05951296).

LTP001, an oral, selectively deuterated form of pirfenidone designed to retain the antifibrotic and anti-inflammatory activity of pirfenidone with a differentiated pharmacokinetic profile (NCT05497284, NCT05321420).

ME-015 (suplatast tosilate) aims to stabilize ion channels in the neuronal endings in the lungs that mediate IPF-related cough (NCT05983471).

Nalbuphine, a small-molecule, dual-mechanism treatment for chronic cough in IPF. It acts as both a mu opioid receptor antagonist and a kappa opioid receptor agonist (NCT05964335). The CANAL trial, complete last year, is evaluating an extended-release formulation (NCT04030026).

NP-120 (ifenprodil), a small-molecule N-methyl-D-aspartate (NMDA) receptor antagonist, specifically targets the NMDA-type subunit 2B (GluN2B) (NCT04318704).

Orvepitant, a selective antagonist for the NK₁ receptor, is being evaluated to treat IPF-related cough (NCT05815089).

RXC007 (zelasudil), a Rho-associated coiled-coil–containing protein kinase 2 (ROCK2) selective inhibitor, was granted FDA orphan drug designation in August 2023 (NCT05570058).

Saracatinib, a selective Src kinase inhibitor originally developed for oncological indications (NCT04598919).

SHR-1906, an intravenous treatment, inhibits binding of a target protein to a variety of cytokines and growth factors, affects downstream signaling pathways, and reduces cell proliferation and migration (NCT05722964).

TTI-101, an oral, small-molecule inhibitor of signal transducer and activator of transcription (STAT3), which has been found to accumulate in the lungs of IPF patients (NCT05671835).

VAY736 (lanalumab), a BAFF-R inhibitor (NCT03287414).

Vixarelimab, a human monoclonal oncastatin M receptor beta antibody (NCT05785624).

Some investigative programs, however, didn’t make it out of phase 2. The trial evaluating inhaled GB0139, a selective functional antagonist of G-protein–coupled receptor 84, which plays a key role in fibrosis, failed to meet its primary endpoint (NCT03832946). Likewise, oral GLPG1205 failed to show a significant difference in FVC decline vs. placebo (NCT03725852). The program to develop SAR156597, also known as romilkimab, was halted (NCT02345070). ND-L02-s0201n, an siRNA oligonucleotide drug designed to inhibit heat shock protein 47 (HSP47), which regulates collagen synthesis and secretion that causes fibrosis, didn’t show the expected efficacy (NCT03538301).
 

Phase 1 trials

No fewer than 27 phase 1 trials are evaluating investigative treatments for IPF, many in the early phase or not yet recruiting. According to GlobalData, phase 1 drugs for IPF have a 66% chance of moving onto phase 2. Among the advanced phase 1 trials that have gained corporate backing are:

9MW3811, an anti–interleukin-11 monoclonal antibody IV injection (NCT05912049).

ANG-3070, an oral tyrosine kinase inhibitor targeting platelet-derived growth factor (PDGFR) alpha and beta (NCT05387785).

C106, an angiotensin II type 2 receptor agonist (NCT05427253).

HuL001, which targets alpha-enolase (NCT04540770).

LTI-03, a Caveolin-1 (Cav1)-related peptide designed to restore Cav1 expression in lung tissue (NCT05954988).

ORIN1001, a first-in-class small molecule that selectively blocks the inositol requiring enzyme 1alphase (IRE1) RNAse and blocks X-box binding protein 1 (XBP1) activation (NCT04643769).

PRS-220 is an orally inhaled anticalin protein targeting connective tissue growth factor (CTGF) (NTC05473533).

TRK-250, a single-strand, long-chain nucleic acid that selectively suppresses expression of transforming growth factor-beta 1 (TGF-beta1) protein (NCT03727802).

“While we have therapies that we’re able to give patients, we need to do more and we need to do better,” Dr. Lee said. “We’re all hopeful the next phase 3 clinical trial will be something that will help change the treatment paradigm for our patients. We’re very patient, and hopefully those that are interested in improving this treatment landscape will continue to persist.”

Dr. Lee disclosed financial relationships with Boehringer Ingelheim, Pliant Therapeutics, Blade Therapeutics, United Therapeutics, Eleven P15. and Avalyn Pharma.

It’s as if hospitals, clinicians, and the health care system itself were unprepared for such success as a powerful multiple-drug regimen emerged for hospitalized patients with heart failure with reduced ejection fraction (HFrEF).

Uptake in practice has been sluggish for the management strategy driven by a quartet of medications, each with its own mechanisms of action, started in the hospital simultaneously or in rapid succession over a few days. Key to the regimen, dosages are at least partly uptitrated in the hospital then optimized during close postdischarge follow-up.

The so-called four pillars of medical therapy for HFrEF, defined by a left ventricular ejection fraction (LVEF) of 40% or lower, include an SGLT2 inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin-system (RAS) inhibitor – preferably sacubitril-valsartan (Entresto) or, as a backup, an ACE inhibitor or angiotensin receptor blocker (ARB).

Academic consensus on the strategy is strong. The approach is consistent with heart failure (HF) guidelines on both sides of the Atlantic and is backed by solid trial evidence suggesting striking improvements in survival, readmission risk, and quality of life.

In HFrEF, the four medications “clearly reduce all-cause mortality, are nonoverlapping and truly and fully additive, and their benefits are cumulative, incremental, and begin within days,” Gregg C. Fonarow, MD, University of California, Los Angeles, said in an interview.

“Yet, when we look at their actual implementation in clinical practice, we’ve seen this slow and variable uptake.”
 

So, why is that?

The STRONG-HF trial tested a version of the multiple-drug strategy and demonstrated what it could achieve even without a contribution from SGLT2 inhibitors, which weren’t yet indicated for HF. Eligibility for the trial, with more than 1,000 patients, wasn’t dependent on their LVEF.

Patients assigned to early and rapidly sequential initiation of a beta-blocker, an MRA, and a RAS inhibitor, compared with a standard-care control group, benefited with a 34% drop (P = .002) in risk for death or HF readmission over the next 6 months.

Few doubt – and the bulk of evidence suggests – that adding an SGLT2 inhibitor to round out the four-pillar strategy would safely boost its clinical potential in HFrEF.

The strategy’s smooth adoption in practice likely has multiple confounders that include clinical inertia, perceptions of HF medical management as a long-term outpatient process, and the onerous and Kafkaesque systems of care and reimbursement in the United States.

For example, the drug initiation and uptitration process may seem too complex for integration into slow-to-change hospital practices. And there could be a misguided sense that the regimen and follow-up must abide by the same exacting detail and standards set forth in, for example, the STRONG-HF protocol.

But starting hospitalized patients with HFrEF on the quartet of drugs and optimizing their dosages in hospital and after discharge can be simpler and more straightforward than that, Dr. Fonarow and other experts explain.

The academic community’s buy-in is a first step, but broader acceptance is frustrated by an “overwhelming culture of clinical care for heart failure” that encourages a more drawn-out process for adding medications, said Stephen J. Greene, MD, Duke Clinical Research Institute, Durham, N.C. “We need to turn our thinking on its head about heart failure in clinical practice.”

The “dramatic” underuse of the four pillars in the hospital stems in part from “outmoded” treatment algorithms that clinicians are following, Dr. Fonarow said. And they have “no sense of urgency,” sometimes wrongly believing “that it takes months for these medications to ultimately kick in.”

For hospitalized patients with HFrEF, “there is an imperative to overcome these timid algorithms and timid thinking,” he said. They should be on “full quadruple therapy” before discharge.

“And for newly diagnosed outpatients, you should essentially give yourself 7 days to get these drugs on board,” he added, either simultaneously or in “very rapid sequence.”

What’s needed is a “cultural shift” in medicine that “elevates heart failure to the same level of urgency that we have in the care of some other disease states,” agreed Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital and Harvard Medical School, Boston.
 

Hospital as opportunity

The patient’s 4-7 days in the hospital typically represent a “wonderful opportunity” to initiate all four drug classes in rapid succession and start uptitrations. But most hospitals and other health care settings, Dr. Vaduganathan observed, lack the structure and systems to support the process. Broad application will require “buy-in from multiple parties – from the clinician, from the patient, their caregivers, and their partners as well as the health system.”

Physician awareness and support for the strategy, suggests at least one of these experts, is probably much less of a challenge to its broad adoption than the bewildering mechanics of health care delivery and reimbursement.

“The problem is not education. The problem is the way that our health care system is structured,” said Milton Packer, MD, Baylor Heart and Vascular Institute, Dallas.

For example, sacubitril-valsartan and the SGLT2 inhibitors are still under patent and are far more expensive than longtime generic beta-blockers and MRAs. That means physicians typically spend valuable time pursuing prior authorizations for the brand-name drugs under pressure to eventually discharge the patient because of limits on hospital reimbursement.

Clinicians in the hospital are “almost disincentivized by the system” to implement management plans that call for early and rapid initiation of multiple drugs, Dr. Vaduganathan pointed out.
 

One change per day

There’s no one formula for carrying out the quadruple drug strategy, Dr. Vaduganathan noted. “I make only a single change per day” to the regimen, such as uptitration or addition of a single agent. That way, tolerability can be evaluated one drug at a time, “and then the following day, I can make the next therapeutic change.”

The order in which the drugs are started mostly does not matter, in contrast to a traditional approach that might have added new drugs in the sequence of their approval for HFrEF or adoption in guidelines. Under that scenario, each successive agent might be fully uptitrated before the next could be brought on board.

Historically, Dr. Packer observed, “you would start with an ACE inhibitor, add a beta-blocker, add an MRA, switch to sacubitril-valsartan, add an SGLT2 inhibitor – and it would take 8 months.” Any prescribed sequence is pointless given the short time frame that is ideal for initiating all the drugs, he said.

Hypothetically, however, there is some rationale for starting them in an order that leverages their unique actions and side effects. For example, Dr. Vaduganathan and others observed, it may be helpful to start an SGLT2 inhibitor and sacubitril-valsartan early in the process, because they can mitigate any hyperkalemia from the subsequent addition of an MRA.

That being said, “I don’t think we have firm evidence that any particular order is more efficacious than another,” Dr. Vaduganathan said. “It’s really about getting patients on all four drugs as quickly as possible, regardless of the sequence.”

Discussions about sequencing the drugs are “a distraction for our field,” Dr. Greene said. In trials, clinical benefit from the multiple-drug regimen has emerged almost right away once the drugs were on board. “The data clearly show that initiating all four, at least at low doses, gives the best bang for your buck and would be a high-yield strategy.”

Best evidence suggests that once all four agents have been started, attention can turn to uptitration, “with the beta-blocker as the higher priority,” Dr. Greene said. “The bottom line is to keep it simple: four drugs, simultaneously or within 1 week, and prioritize initiation at low doses to maximize tolerability.”

The four-drug approach yields survival and rehospitalization benefits even when uptitrations don’t reach prespecified goals, Dr. Fonarow observed. The SGLT2 inhibitors are started and maintained at the same dosage. But for the other three agents, uptitration should aim for the highest well-tolerated level, up to the target, even if the highest tolerated is the initial dosage.
 

‘Challenging to generalize’

The goal in STRONG-HF was to start and at least partly uptitrate a beta-blocker, an MRA, and sacubitril-valsartan in the hospital and fully optimize their dosages within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were closely monitored at four in-person evaluations during the first 6 outpatient weeks.

But few believe the trial’s intensive drug regimen and postdischarge follow-up, as stipulated in the protocol, would be tolerated by current systems of care and reimbursement.

STRONG-HF “affirms the strategy in a rigorous, well conducted way,” Dr. Vaduganathan said, but would be “challenging to generalize to all health care systems.”

As a result, some in the field are “quick to almost disregard STRONG-HF in its entirety” and consider it “wishful thinking,” Dr. Greene said. Better that providers not become distracted by the precise details of its protocol.

At Duke, he said, “we see all our patients within 1 week of discharge to ensure they’re doing okay in terms of volume status and look for opportunities to escalate their guideline-directed medical therapy.”

But that can be done without in-person visits. A lot of the follow-up and uptitrations, Dr. Greene said, can be achieved by telephone or at virtual appointments in conjunction with regular laboratory testing. “That, I think, really is the path for the future, in this age when clinics are overwhelmed by in-person visits.”
 

Mildly reduced and preserved EF

STRONG-HF, in which patients were enrolled without regard to ejection fraction, suggests that its rapidly sequential drug regimen and intensive management protocol improves outcomes for patients with HF at any level of LVEF.

Those findings and others, along with DELIVER, EMPEROR-Preserved and other studies, make a tantalizing case for the quadruple drug approach in patients with HF and LVEF >40% – that is, those with mildly reduced (LVEF > 40% to < 50%, HFmrEF) or preserved LVEF > 50%, HFpEF) ejection fraction.

But the case isn’t solid enough to declare the four agents as core therapy for HF and LVEF > 40%, observed Dr. Vaduganathan. Currently, SGLT2 inhibitors “are the only drug class that we are routinely implementing” in HFmrEF and HFpEF.

There have been suggestions of clinical benefit for such patients with sacubitril-valsartan and MRAs, especially in PARAGON-HF and TOPCAT, respectively. The evidence is stronger in HFmrEF than in HFpEF, but in either case it’s weaker than the clear-cut trial support for SGLT2 inhibitors in those HF categories.

Trials also suggest that in HF with LVEF > 40%, clinical benefits from RAS inhibitors and MRAs taper off with increasing ejection fraction, especially into the > 60% range.

In both HFmrEF and HFpEF, “I routinely try to get the patient on an SGLT2 inhibitor rapidly and then treat with some of the other agents on a more individual basis,” Dr. Vaduganathan said. An LVEF in the HFmrEF range, for example, would likely call for the addition of an MRA and sacubitril-valsartan.

Dr. Packer said he would likely recommend all four agents for patients with HF and LVEF up to 60%, which he considers a more appropriate definition of HFrEF. Their clinical benefits appear consistent across that LVEF range, he said, although they thin out somewhat at the higher end.

Evidence supporting the four pillars in HF with LV > 40% and < 60% is weakest for beta-blockers, Dr. Packer noted, so arguably those drugs could be left out of the mix for patients with ejection fractions in that range.

Dr. Fonarow reported ties with Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr. Greene disclosed ties with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Bristol-Myers Squibb, Corteria, CSL Vifor, Cytokinetics, Lexicon Merck, Novartis, Pfizer, PharmaIN, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals. Dr. Vaduganathan disclosed ties with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Galmed, Impulse Dynamics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Occlutech, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health. Dr. Packer disclosed relationships with 89bio, AbbVie, Actavis, Amarin, Amgen, AstraZeneca, Attralus, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Medtronic, Moderna, Novartis, Pharmacosmos, Reata, Regeneron, Relypsa, and Salamandra.
 

A version of this article first appeared on Medscape.com.

It’s as if hospitals, clinicians, and the health care system itself were unprepared for such success as a powerful multiple-drug regimen emerged for hospitalized patients with heart failure with reduced ejection fraction (HFrEF).

Uptake in practice has been sluggish for the management strategy driven by a quartet of medications, each with its own mechanisms of action, started in the hospital simultaneously or in rapid succession over a few days. Key to the regimen, dosages are at least partly uptitrated in the hospital then optimized during close postdischarge follow-up.

The so-called four pillars of medical therapy for HFrEF, defined by a left ventricular ejection fraction (LVEF) of 40% or lower, include an SGLT2 inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin-system (RAS) inhibitor – preferably sacubitril-valsartan (Entresto) or, as a backup, an ACE inhibitor or angiotensin receptor blocker (ARB).

Academic consensus on the strategy is strong. The approach is consistent with heart failure (HF) guidelines on both sides of the Atlantic and is backed by solid trial evidence suggesting striking improvements in survival, readmission risk, and quality of life.

In HFrEF, the four medications “clearly reduce all-cause mortality, are nonoverlapping and truly and fully additive, and their benefits are cumulative, incremental, and begin within days,” Gregg C. Fonarow, MD, University of California, Los Angeles, said in an interview.

“Yet, when we look at their actual implementation in clinical practice, we’ve seen this slow and variable uptake.”
 

So, why is that?

The STRONG-HF trial tested a version of the multiple-drug strategy and demonstrated what it could achieve even without a contribution from SGLT2 inhibitors, which weren’t yet indicated for HF. Eligibility for the trial, with more than 1,000 patients, wasn’t dependent on their LVEF.

Patients assigned to early and rapidly sequential initiation of a beta-blocker, an MRA, and a RAS inhibitor, compared with a standard-care control group, benefited with a 34% drop (P = .002) in risk for death or HF readmission over the next 6 months.

Few doubt – and the bulk of evidence suggests – that adding an SGLT2 inhibitor to round out the four-pillar strategy would safely boost its clinical potential in HFrEF.

The strategy’s smooth adoption in practice likely has multiple confounders that include clinical inertia, perceptions of HF medical management as a long-term outpatient process, and the onerous and Kafkaesque systems of care and reimbursement in the United States.

For example, the drug initiation and uptitration process may seem too complex for integration into slow-to-change hospital practices. And there could be a misguided sense that the regimen and follow-up must abide by the same exacting detail and standards set forth in, for example, the STRONG-HF protocol.

But starting hospitalized patients with HFrEF on the quartet of drugs and optimizing their dosages in hospital and after discharge can be simpler and more straightforward than that, Dr. Fonarow and other experts explain.

The academic community’s buy-in is a first step, but broader acceptance is frustrated by an “overwhelming culture of clinical care for heart failure” that encourages a more drawn-out process for adding medications, said Stephen J. Greene, MD, Duke Clinical Research Institute, Durham, N.C. “We need to turn our thinking on its head about heart failure in clinical practice.”

The “dramatic” underuse of the four pillars in the hospital stems in part from “outmoded” treatment algorithms that clinicians are following, Dr. Fonarow said. And they have “no sense of urgency,” sometimes wrongly believing “that it takes months for these medications to ultimately kick in.”

For hospitalized patients with HFrEF, “there is an imperative to overcome these timid algorithms and timid thinking,” he said. They should be on “full quadruple therapy” before discharge.

“And for newly diagnosed outpatients, you should essentially give yourself 7 days to get these drugs on board,” he added, either simultaneously or in “very rapid sequence.”

What’s needed is a “cultural shift” in medicine that “elevates heart failure to the same level of urgency that we have in the care of some other disease states,” agreed Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital and Harvard Medical School, Boston.
 

Hospital as opportunity

The patient’s 4-7 days in the hospital typically represent a “wonderful opportunity” to initiate all four drug classes in rapid succession and start uptitrations. But most hospitals and other health care settings, Dr. Vaduganathan observed, lack the structure and systems to support the process. Broad application will require “buy-in from multiple parties – from the clinician, from the patient, their caregivers, and their partners as well as the health system.”

Physician awareness and support for the strategy, suggests at least one of these experts, is probably much less of a challenge to its broad adoption than the bewildering mechanics of health care delivery and reimbursement.

“The problem is not education. The problem is the way that our health care system is structured,” said Milton Packer, MD, Baylor Heart and Vascular Institute, Dallas.

For example, sacubitril-valsartan and the SGLT2 inhibitors are still under patent and are far more expensive than longtime generic beta-blockers and MRAs. That means physicians typically spend valuable time pursuing prior authorizations for the brand-name drugs under pressure to eventually discharge the patient because of limits on hospital reimbursement.

Clinicians in the hospital are “almost disincentivized by the system” to implement management plans that call for early and rapid initiation of multiple drugs, Dr. Vaduganathan pointed out.
 

One change per day

There’s no one formula for carrying out the quadruple drug strategy, Dr. Vaduganathan noted. “I make only a single change per day” to the regimen, such as uptitration or addition of a single agent. That way, tolerability can be evaluated one drug at a time, “and then the following day, I can make the next therapeutic change.”

The order in which the drugs are started mostly does not matter, in contrast to a traditional approach that might have added new drugs in the sequence of their approval for HFrEF or adoption in guidelines. Under that scenario, each successive agent might be fully uptitrated before the next could be brought on board.

Historically, Dr. Packer observed, “you would start with an ACE inhibitor, add a beta-blocker, add an MRA, switch to sacubitril-valsartan, add an SGLT2 inhibitor – and it would take 8 months.” Any prescribed sequence is pointless given the short time frame that is ideal for initiating all the drugs, he said.

Hypothetically, however, there is some rationale for starting them in an order that leverages their unique actions and side effects. For example, Dr. Vaduganathan and others observed, it may be helpful to start an SGLT2 inhibitor and sacubitril-valsartan early in the process, because they can mitigate any hyperkalemia from the subsequent addition of an MRA.

That being said, “I don’t think we have firm evidence that any particular order is more efficacious than another,” Dr. Vaduganathan said. “It’s really about getting patients on all four drugs as quickly as possible, regardless of the sequence.”

Discussions about sequencing the drugs are “a distraction for our field,” Dr. Greene said. In trials, clinical benefit from the multiple-drug regimen has emerged almost right away once the drugs were on board. “The data clearly show that initiating all four, at least at low doses, gives the best bang for your buck and would be a high-yield strategy.”

Best evidence suggests that once all four agents have been started, attention can turn to uptitration, “with the beta-blocker as the higher priority,” Dr. Greene said. “The bottom line is to keep it simple: four drugs, simultaneously or within 1 week, and prioritize initiation at low doses to maximize tolerability.”

The four-drug approach yields survival and rehospitalization benefits even when uptitrations don’t reach prespecified goals, Dr. Fonarow observed. The SGLT2 inhibitors are started and maintained at the same dosage. But for the other three agents, uptitration should aim for the highest well-tolerated level, up to the target, even if the highest tolerated is the initial dosage.
 

‘Challenging to generalize’

The goal in STRONG-HF was to start and at least partly uptitrate a beta-blocker, an MRA, and sacubitril-valsartan in the hospital and fully optimize their dosages within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were closely monitored at four in-person evaluations during the first 6 outpatient weeks.

But few believe the trial’s intensive drug regimen and postdischarge follow-up, as stipulated in the protocol, would be tolerated by current systems of care and reimbursement.

STRONG-HF “affirms the strategy in a rigorous, well conducted way,” Dr. Vaduganathan said, but would be “challenging to generalize to all health care systems.”

As a result, some in the field are “quick to almost disregard STRONG-HF in its entirety” and consider it “wishful thinking,” Dr. Greene said. Better that providers not become distracted by the precise details of its protocol.

At Duke, he said, “we see all our patients within 1 week of discharge to ensure they’re doing okay in terms of volume status and look for opportunities to escalate their guideline-directed medical therapy.”

But that can be done without in-person visits. A lot of the follow-up and uptitrations, Dr. Greene said, can be achieved by telephone or at virtual appointments in conjunction with regular laboratory testing. “That, I think, really is the path for the future, in this age when clinics are overwhelmed by in-person visits.”
 

Mildly reduced and preserved EF

STRONG-HF, in which patients were enrolled without regard to ejection fraction, suggests that its rapidly sequential drug regimen and intensive management protocol improves outcomes for patients with HF at any level of LVEF.

Those findings and others, along with DELIVER, EMPEROR-Preserved and other studies, make a tantalizing case for the quadruple drug approach in patients with HF and LVEF >40% – that is, those with mildly reduced (LVEF > 40% to < 50%, HFmrEF) or preserved LVEF > 50%, HFpEF) ejection fraction.

But the case isn’t solid enough to declare the four agents as core therapy for HF and LVEF > 40%, observed Dr. Vaduganathan. Currently, SGLT2 inhibitors “are the only drug class that we are routinely implementing” in HFmrEF and HFpEF.

There have been suggestions of clinical benefit for such patients with sacubitril-valsartan and MRAs, especially in PARAGON-HF and TOPCAT, respectively. The evidence is stronger in HFmrEF than in HFpEF, but in either case it’s weaker than the clear-cut trial support for SGLT2 inhibitors in those HF categories.

Trials also suggest that in HF with LVEF > 40%, clinical benefits from RAS inhibitors and MRAs taper off with increasing ejection fraction, especially into the > 60% range.

In both HFmrEF and HFpEF, “I routinely try to get the patient on an SGLT2 inhibitor rapidly and then treat with some of the other agents on a more individual basis,” Dr. Vaduganathan said. An LVEF in the HFmrEF range, for example, would likely call for the addition of an MRA and sacubitril-valsartan.

Dr. Packer said he would likely recommend all four agents for patients with HF and LVEF up to 60%, which he considers a more appropriate definition of HFrEF. Their clinical benefits appear consistent across that LVEF range, he said, although they thin out somewhat at the higher end.

Evidence supporting the four pillars in HF with LV > 40% and < 60% is weakest for beta-blockers, Dr. Packer noted, so arguably those drugs could be left out of the mix for patients with ejection fractions in that range.

Dr. Fonarow reported ties with Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr. Greene disclosed ties with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Bristol-Myers Squibb, Corteria, CSL Vifor, Cytokinetics, Lexicon Merck, Novartis, Pfizer, PharmaIN, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals. Dr. Vaduganathan disclosed ties with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Galmed, Impulse Dynamics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Occlutech, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health. Dr. Packer disclosed relationships with 89bio, AbbVie, Actavis, Amarin, Amgen, AstraZeneca, Attralus, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Medtronic, Moderna, Novartis, Pharmacosmos, Reata, Regeneron, Relypsa, and Salamandra.
 

A version of this article first appeared on Medscape.com.

It’s as if hospitals, clinicians, and the health care system itself were unprepared for such success as a powerful multiple-drug regimen emerged for hospitalized patients with heart failure with reduced ejection fraction (HFrEF).

Uptake in practice has been sluggish for the management strategy driven by a quartet of medications, each with its own mechanisms of action, started in the hospital simultaneously or in rapid succession over a few days. Key to the regimen, dosages are at least partly uptitrated in the hospital then optimized during close postdischarge follow-up.

The so-called four pillars of medical therapy for HFrEF, defined by a left ventricular ejection fraction (LVEF) of 40% or lower, include an SGLT2 inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin-system (RAS) inhibitor – preferably sacubitril-valsartan (Entresto) or, as a backup, an ACE inhibitor or angiotensin receptor blocker (ARB).

Academic consensus on the strategy is strong. The approach is consistent with heart failure (HF) guidelines on both sides of the Atlantic and is backed by solid trial evidence suggesting striking improvements in survival, readmission risk, and quality of life.

In HFrEF, the four medications “clearly reduce all-cause mortality, are nonoverlapping and truly and fully additive, and their benefits are cumulative, incremental, and begin within days,” Gregg C. Fonarow, MD, University of California, Los Angeles, said in an interview.

“Yet, when we look at their actual implementation in clinical practice, we’ve seen this slow and variable uptake.”
 

So, why is that?

The STRONG-HF trial tested a version of the multiple-drug strategy and demonstrated what it could achieve even without a contribution from SGLT2 inhibitors, which weren’t yet indicated for HF. Eligibility for the trial, with more than 1,000 patients, wasn’t dependent on their LVEF.

Patients assigned to early and rapidly sequential initiation of a beta-blocker, an MRA, and a RAS inhibitor, compared with a standard-care control group, benefited with a 34% drop (P = .002) in risk for death or HF readmission over the next 6 months.

Few doubt – and the bulk of evidence suggests – that adding an SGLT2 inhibitor to round out the four-pillar strategy would safely boost its clinical potential in HFrEF.

The strategy’s smooth adoption in practice likely has multiple confounders that include clinical inertia, perceptions of HF medical management as a long-term outpatient process, and the onerous and Kafkaesque systems of care and reimbursement in the United States.

For example, the drug initiation and uptitration process may seem too complex for integration into slow-to-change hospital practices. And there could be a misguided sense that the regimen and follow-up must abide by the same exacting detail and standards set forth in, for example, the STRONG-HF protocol.

But starting hospitalized patients with HFrEF on the quartet of drugs and optimizing their dosages in hospital and after discharge can be simpler and more straightforward than that, Dr. Fonarow and other experts explain.

The academic community’s buy-in is a first step, but broader acceptance is frustrated by an “overwhelming culture of clinical care for heart failure” that encourages a more drawn-out process for adding medications, said Stephen J. Greene, MD, Duke Clinical Research Institute, Durham, N.C. “We need to turn our thinking on its head about heart failure in clinical practice.”

The “dramatic” underuse of the four pillars in the hospital stems in part from “outmoded” treatment algorithms that clinicians are following, Dr. Fonarow said. And they have “no sense of urgency,” sometimes wrongly believing “that it takes months for these medications to ultimately kick in.”

For hospitalized patients with HFrEF, “there is an imperative to overcome these timid algorithms and timid thinking,” he said. They should be on “full quadruple therapy” before discharge.

“And for newly diagnosed outpatients, you should essentially give yourself 7 days to get these drugs on board,” he added, either simultaneously or in “very rapid sequence.”

What’s needed is a “cultural shift” in medicine that “elevates heart failure to the same level of urgency that we have in the care of some other disease states,” agreed Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital and Harvard Medical School, Boston.
 

Hospital as opportunity

The patient’s 4-7 days in the hospital typically represent a “wonderful opportunity” to initiate all four drug classes in rapid succession and start uptitrations. But most hospitals and other health care settings, Dr. Vaduganathan observed, lack the structure and systems to support the process. Broad application will require “buy-in from multiple parties – from the clinician, from the patient, their caregivers, and their partners as well as the health system.”

Physician awareness and support for the strategy, suggests at least one of these experts, is probably much less of a challenge to its broad adoption than the bewildering mechanics of health care delivery and reimbursement.

“The problem is not education. The problem is the way that our health care system is structured,” said Milton Packer, MD, Baylor Heart and Vascular Institute, Dallas.

For example, sacubitril-valsartan and the SGLT2 inhibitors are still under patent and are far more expensive than longtime generic beta-blockers and MRAs. That means physicians typically spend valuable time pursuing prior authorizations for the brand-name drugs under pressure to eventually discharge the patient because of limits on hospital reimbursement.

Clinicians in the hospital are “almost disincentivized by the system” to implement management plans that call for early and rapid initiation of multiple drugs, Dr. Vaduganathan pointed out.
 

One change per day

There’s no one formula for carrying out the quadruple drug strategy, Dr. Vaduganathan noted. “I make only a single change per day” to the regimen, such as uptitration or addition of a single agent. That way, tolerability can be evaluated one drug at a time, “and then the following day, I can make the next therapeutic change.”

The order in which the drugs are started mostly does not matter, in contrast to a traditional approach that might have added new drugs in the sequence of their approval for HFrEF or adoption in guidelines. Under that scenario, each successive agent might be fully uptitrated before the next could be brought on board.

Historically, Dr. Packer observed, “you would start with an ACE inhibitor, add a beta-blocker, add an MRA, switch to sacubitril-valsartan, add an SGLT2 inhibitor – and it would take 8 months.” Any prescribed sequence is pointless given the short time frame that is ideal for initiating all the drugs, he said.

Hypothetically, however, there is some rationale for starting them in an order that leverages their unique actions and side effects. For example, Dr. Vaduganathan and others observed, it may be helpful to start an SGLT2 inhibitor and sacubitril-valsartan early in the process, because they can mitigate any hyperkalemia from the subsequent addition of an MRA.

That being said, “I don’t think we have firm evidence that any particular order is more efficacious than another,” Dr. Vaduganathan said. “It’s really about getting patients on all four drugs as quickly as possible, regardless of the sequence.”

Discussions about sequencing the drugs are “a distraction for our field,” Dr. Greene said. In trials, clinical benefit from the multiple-drug regimen has emerged almost right away once the drugs were on board. “The data clearly show that initiating all four, at least at low doses, gives the best bang for your buck and would be a high-yield strategy.”

Best evidence suggests that once all four agents have been started, attention can turn to uptitration, “with the beta-blocker as the higher priority,” Dr. Greene said. “The bottom line is to keep it simple: four drugs, simultaneously or within 1 week, and prioritize initiation at low doses to maximize tolerability.”

The four-drug approach yields survival and rehospitalization benefits even when uptitrations don’t reach prespecified goals, Dr. Fonarow observed. The SGLT2 inhibitors are started and maintained at the same dosage. But for the other three agents, uptitration should aim for the highest well-tolerated level, up to the target, even if the highest tolerated is the initial dosage.
 

‘Challenging to generalize’

The goal in STRONG-HF was to start and at least partly uptitrate a beta-blocker, an MRA, and sacubitril-valsartan in the hospital and fully optimize their dosages within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were closely monitored at four in-person evaluations during the first 6 outpatient weeks.

But few believe the trial’s intensive drug regimen and postdischarge follow-up, as stipulated in the protocol, would be tolerated by current systems of care and reimbursement.

STRONG-HF “affirms the strategy in a rigorous, well conducted way,” Dr. Vaduganathan said, but would be “challenging to generalize to all health care systems.”

As a result, some in the field are “quick to almost disregard STRONG-HF in its entirety” and consider it “wishful thinking,” Dr. Greene said. Better that providers not become distracted by the precise details of its protocol.

At Duke, he said, “we see all our patients within 1 week of discharge to ensure they’re doing okay in terms of volume status and look for opportunities to escalate their guideline-directed medical therapy.”

But that can be done without in-person visits. A lot of the follow-up and uptitrations, Dr. Greene said, can be achieved by telephone or at virtual appointments in conjunction with regular laboratory testing. “That, I think, really is the path for the future, in this age when clinics are overwhelmed by in-person visits.”
 

Mildly reduced and preserved EF

STRONG-HF, in which patients were enrolled without regard to ejection fraction, suggests that its rapidly sequential drug regimen and intensive management protocol improves outcomes for patients with HF at any level of LVEF.

Those findings and others, along with DELIVER, EMPEROR-Preserved and other studies, make a tantalizing case for the quadruple drug approach in patients with HF and LVEF >40% – that is, those with mildly reduced (LVEF > 40% to < 50%, HFmrEF) or preserved LVEF > 50%, HFpEF) ejection fraction.

But the case isn’t solid enough to declare the four agents as core therapy for HF and LVEF > 40%, observed Dr. Vaduganathan. Currently, SGLT2 inhibitors “are the only drug class that we are routinely implementing” in HFmrEF and HFpEF.

There have been suggestions of clinical benefit for such patients with sacubitril-valsartan and MRAs, especially in PARAGON-HF and TOPCAT, respectively. The evidence is stronger in HFmrEF than in HFpEF, but in either case it’s weaker than the clear-cut trial support for SGLT2 inhibitors in those HF categories.

Trials also suggest that in HF with LVEF > 40%, clinical benefits from RAS inhibitors and MRAs taper off with increasing ejection fraction, especially into the > 60% range.

In both HFmrEF and HFpEF, “I routinely try to get the patient on an SGLT2 inhibitor rapidly and then treat with some of the other agents on a more individual basis,” Dr. Vaduganathan said. An LVEF in the HFmrEF range, for example, would likely call for the addition of an MRA and sacubitril-valsartan.

Dr. Packer said he would likely recommend all four agents for patients with HF and LVEF up to 60%, which he considers a more appropriate definition of HFrEF. Their clinical benefits appear consistent across that LVEF range, he said, although they thin out somewhat at the higher end.

Evidence supporting the four pillars in HF with LV > 40% and < 60% is weakest for beta-blockers, Dr. Packer noted, so arguably those drugs could be left out of the mix for patients with ejection fractions in that range.

Dr. Fonarow reported ties with Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr. Greene disclosed ties with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Bristol-Myers Squibb, Corteria, CSL Vifor, Cytokinetics, Lexicon Merck, Novartis, Pfizer, PharmaIN, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals. Dr. Vaduganathan disclosed ties with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Galmed, Impulse Dynamics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Occlutech, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health. Dr. Packer disclosed relationships with 89bio, AbbVie, Actavis, Amarin, Amgen, AstraZeneca, Attralus, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Medtronic, Moderna, Novartis, Pharmacosmos, Reata, Regeneron, Relypsa, and Salamandra.
 

A version of this article first appeared on Medscape.com.

A noteworthy shift recently occurred in the field of hepatology, but it didn’t stem from a clinical trial or medical finding. Instead, the change arose from a matter of semantics.

In a special article published online in the journal Hepatology, a diverse international consensus group introduced new terminology for one of the world’s most rapidly growing diseases.

The term nonalcoholic fatty liver disease (NAFLD) was to be officially retired, replaced with a more precise and descriptive term – metabolic dysfunction–associated steatotic liver disease (MASLD).

In addition, steatotic liver disease (SLD) would be used as an umbrella term encompassing both MASLD and a new subcategory, MetALD, for individuals with MASLD whose alcohol consumption ranges from 140 to 350 g/wk for women and from 210 to 420 g/wk for men. Nonalcoholic steatohepatitis (NASH) would be known as metabolic dysfunction-associated steatohepatitis (MASH).

The new terminology represents small changes with significant implications, especially for patients with MetALD, said the NAFLD nomenclature consensus group’s co-lead, Mary E. Rinella, MD, professor of medicine at University of Chicago and director of the metabolic and fatty liver program at University of Chicago Hospitals.

“The only really new thing we did is identify a group of people who meet criteria for MASLD and also drink more than the allowable limit,” she said. “There are tons of these patients who were not being considered before. Now they’re in a category by themselves, where they are going to be able to be studied and better understood.”
 

Why make a change?

The unveiling of the new nomenclature marked the culmination of 3 years of dedicated work that was built upon decades of growing understanding about the pathophysiologic underpinnings of these disease states.

The terms NAFLD and NASH emerged in 1980 to describe patients with chronic liver disease who denied excessive alcohol consumption. However, in the past 2 decades, it became increasingly evident that the existing terminology was inadequate, the consensus group’s co-lead, Philip Newsome, PhD, said in an interview.

“There was a strong desire for a name that describes what the condition is, rather than what it isn’t; avoiding use of stigmatizing terms, such as fatty and alcoholic; and finally, a nomenclature that could recognize the coexistence of conditions,” said Dr. Newsome, former secretary general of the European Association for the Study of the Liver (EASL), and director of the Centre for Liver and Gastrointestinal Research at the University of Birmingham, England.

These forces, combined with the recognition that NAFLD and alcohol-related liver disease shared biological processes, created momentum for change.

The idea gained traction with a 2020 article that proposed “MAFLD” as a more suitable term because it would link the disease with its known cardiometabolic risks, Dr. Rinella explained.

“We thought that paper was going to be the beginning of a conversation, but what happened instead is it became a full-court press,” Dr. Rinella said.

Dr. Rinella and Dr. Newsome then spearheaded a study to determine whether content experts and patients supported change. The process was led by three prominent international liver societies: EASL, the American Association for the Study of Liver Diseases (AASLD), and the Asociación Latinoamericana para el Estudio del Hígado. The organizations received input from 236 panelists from 56 countries, reflecting the diverse voices essential for addressing a disease with an expanding global prevalence rate.

In this globalized world, you cannot make a decision from on high and then expect everybody to just adopt it, Dr. Rinella noted.

The panel utilized a modified Delphi consensus approach, necessitating a supermajority of respondents (67%) to vote in favor of the changes. Seventy-four percent felt that the current nomenclature was sufficiently flawed to consider a name change, and 89% preferred terminology that describes the underlying cause of the disease. A supermajority felt that having “metabolic disease or dysfunction” in the name would help patients better understand their disease (72%) and help health care professionals better explain or understand the disease (80%).

The participants settled on the new terminology, and the study resulted in a conclusion: “The new nomenclature and diagnostic criteria are widely supported, nonstigmatizing, and can improve awareness and patient identification.”

It was by no means a simple or straightforward task, according to Dr. Rinella. “Anytime you have a contentious issue and you engage a broad range of stakeholders, many of which you know are in disagreement, you’re going to have a difficult time reaching consensus,” she said.
 

Reassuring reluctant adopters

The backing of international liver societies will be crucial to ensuring the smooth and relatively swift adoption of the new nomenclature. The AASLD announced in July that it would begin this process by holding conversations with key stakeholders, including the Food and Drug Administration, patient organizations, and pharmaceutical industry representatives.

“By engaging external groups, we have gained valuable insights into potential roadblocks or barriers that may impede the full implementation of the new MASLD nomenclature,” AASLD President Norah Terrault, MD, MPH, FAASLD, told this news organization. “Knowing the types of issues they face will allow us to build an implementation plan that will help guide the field through adoption.”

Even with buy-in from key stakeholders, implementing the changes will be no small feat. It’s a “vast undertaking” that may result in short-term frustrations for some groups, Dr. Terrault said.

“For instance, researchers whose work commenced under the old nomenclature may not be able to alter their research papers and will need to publish under the old nomenclature, which may impact which journals their research could be published in,” she said. “Some patient advocacy groups may have the old nomenclature in their names, resulting in a need to rebrand and revise their educational resources. Patient materials need to be updated. Primary care professionals need to be educated. The list goes on.”

These changes demand both patience and time, Dr. Terrault said. This applies to those tasked with persuading colleagues and patients, as well as clinicians, many of whom have already expressed some resistance to the updated terminology.

The panel anticipated pushback from clinicians who still advocate for NAFLD. However, Dr. Rinella countered that a diagnosis of MASLD requires only one cardiometabolic risk factor and has 99% overlap in most populations. In contrast, the MAFLD diagnostic criteria put forward in 2020 proposed even more restrictive cardiometabolic criteria and greater tolerance for alcohol consumption and would alter the disease natural history, she said.

Concerns have also been raised that replacing NAFLD with MASLD might complicate the value of prior research efforts. However, this should not be a cause for concern, as extensive examination across multiple populations has demonstrated near complete overlap between the two definitions, Dr. Rinella said. Biomarker development, natural history studies, and drug development research will remain unaffected, she said.

Some detractors argue that the term “fatty” is sufficiently descriptive and not stigmatizing. However, Dr. Newsome contends that the panel’s research unequivocally disproves this notion.

“Our Delphi process demonstrated very clearly that over 50% felt it was stigmatizing, and in particular, there were clear supportive views for this change from many patient groups,” he noted. “The new nomenclature empowers patients to explain what the condition means without the use of emotional language.”
 

An opportunity to improve care

One compelling way to persuade reluctant adopters of the new nomenclature’s value is to highlight the opportunities it presents.

The updated terminology opens avenues for research and clinical improvements for patients who meet MASLD criteria and consume alcohol at higher levels (MetALD), Dr. Newsome said.

“There are questions about the relative contribution of these two factors to liver injury, and I see this as an opportunity to explore this area further,” he said.

Hepatologists should embrace this change as a means of increasing awareness regarding the metabolic origins of the disease, Dr. Rinella said. This, in turn, will help identify more patients who require treatment but who are currently overlooked by the existing system, she noted.

“Right now, only around 1% of people with advanced disease are being identified by primary care physicians,” she said. “Hopefully, by elevating the role of metabolic disease, primary care physicians, endocrinologists, and gastroenterologists will be able to identify more patients and bring them to care before they develop cirrhosis.”

Such an outcome would signify much more than a mere semantic shift; it would represent a major advancement in the diagnosis and management of the disease.

A version of this article appeared on Medscape.com.

A noteworthy shift recently occurred in the field of hepatology, but it didn’t stem from a clinical trial or medical finding. Instead, the change arose from a matter of semantics.

In a special article published online in the journal Hepatology, a diverse international consensus group introduced new terminology for one of the world’s most rapidly growing diseases.

The term nonalcoholic fatty liver disease (NAFLD) was to be officially retired, replaced with a more precise and descriptive term – metabolic dysfunction–associated steatotic liver disease (MASLD).

In addition, steatotic liver disease (SLD) would be used as an umbrella term encompassing both MASLD and a new subcategory, MetALD, for individuals with MASLD whose alcohol consumption ranges from 140 to 350 g/wk for women and from 210 to 420 g/wk for men. Nonalcoholic steatohepatitis (NASH) would be known as metabolic dysfunction-associated steatohepatitis (MASH).

The new terminology represents small changes with significant implications, especially for patients with MetALD, said the NAFLD nomenclature consensus group’s co-lead, Mary E. Rinella, MD, professor of medicine at University of Chicago and director of the metabolic and fatty liver program at University of Chicago Hospitals.

“The only really new thing we did is identify a group of people who meet criteria for MASLD and also drink more than the allowable limit,” she said. “There are tons of these patients who were not being considered before. Now they’re in a category by themselves, where they are going to be able to be studied and better understood.”
 

Why make a change?

The unveiling of the new nomenclature marked the culmination of 3 years of dedicated work that was built upon decades of growing understanding about the pathophysiologic underpinnings of these disease states.

The terms NAFLD and NASH emerged in 1980 to describe patients with chronic liver disease who denied excessive alcohol consumption. However, in the past 2 decades, it became increasingly evident that the existing terminology was inadequate, the consensus group’s co-lead, Philip Newsome, PhD, said in an interview.

“There was a strong desire for a name that describes what the condition is, rather than what it isn’t; avoiding use of stigmatizing terms, such as fatty and alcoholic; and finally, a nomenclature that could recognize the coexistence of conditions,” said Dr. Newsome, former secretary general of the European Association for the Study of the Liver (EASL), and director of the Centre for Liver and Gastrointestinal Research at the University of Birmingham, England.

These forces, combined with the recognition that NAFLD and alcohol-related liver disease shared biological processes, created momentum for change.

The idea gained traction with a 2020 article that proposed “MAFLD” as a more suitable term because it would link the disease with its known cardiometabolic risks, Dr. Rinella explained.

“We thought that paper was going to be the beginning of a conversation, but what happened instead is it became a full-court press,” Dr. Rinella said.

Dr. Rinella and Dr. Newsome then spearheaded a study to determine whether content experts and patients supported change. The process was led by three prominent international liver societies: EASL, the American Association for the Study of Liver Diseases (AASLD), and the Asociación Latinoamericana para el Estudio del Hígado. The organizations received input from 236 panelists from 56 countries, reflecting the diverse voices essential for addressing a disease with an expanding global prevalence rate.

In this globalized world, you cannot make a decision from on high and then expect everybody to just adopt it, Dr. Rinella noted.

The panel utilized a modified Delphi consensus approach, necessitating a supermajority of respondents (67%) to vote in favor of the changes. Seventy-four percent felt that the current nomenclature was sufficiently flawed to consider a name change, and 89% preferred terminology that describes the underlying cause of the disease. A supermajority felt that having “metabolic disease or dysfunction” in the name would help patients better understand their disease (72%) and help health care professionals better explain or understand the disease (80%).

The participants settled on the new terminology, and the study resulted in a conclusion: “The new nomenclature and diagnostic criteria are widely supported, nonstigmatizing, and can improve awareness and patient identification.”

It was by no means a simple or straightforward task, according to Dr. Rinella. “Anytime you have a contentious issue and you engage a broad range of stakeholders, many of which you know are in disagreement, you’re going to have a difficult time reaching consensus,” she said.
 

Reassuring reluctant adopters

The backing of international liver societies will be crucial to ensuring the smooth and relatively swift adoption of the new nomenclature. The AASLD announced in July that it would begin this process by holding conversations with key stakeholders, including the Food and Drug Administration, patient organizations, and pharmaceutical industry representatives.

“By engaging external groups, we have gained valuable insights into potential roadblocks or barriers that may impede the full implementation of the new MASLD nomenclature,” AASLD President Norah Terrault, MD, MPH, FAASLD, told this news organization. “Knowing the types of issues they face will allow us to build an implementation plan that will help guide the field through adoption.”

Even with buy-in from key stakeholders, implementing the changes will be no small feat. It’s a “vast undertaking” that may result in short-term frustrations for some groups, Dr. Terrault said.

“For instance, researchers whose work commenced under the old nomenclature may not be able to alter their research papers and will need to publish under the old nomenclature, which may impact which journals their research could be published in,” she said. “Some patient advocacy groups may have the old nomenclature in their names, resulting in a need to rebrand and revise their educational resources. Patient materials need to be updated. Primary care professionals need to be educated. The list goes on.”

These changes demand both patience and time, Dr. Terrault said. This applies to those tasked with persuading colleagues and patients, as well as clinicians, many of whom have already expressed some resistance to the updated terminology.

The panel anticipated pushback from clinicians who still advocate for NAFLD. However, Dr. Rinella countered that a diagnosis of MASLD requires only one cardiometabolic risk factor and has 99% overlap in most populations. In contrast, the MAFLD diagnostic criteria put forward in 2020 proposed even more restrictive cardiometabolic criteria and greater tolerance for alcohol consumption and would alter the disease natural history, she said.

Concerns have also been raised that replacing NAFLD with MASLD might complicate the value of prior research efforts. However, this should not be a cause for concern, as extensive examination across multiple populations has demonstrated near complete overlap between the two definitions, Dr. Rinella said. Biomarker development, natural history studies, and drug development research will remain unaffected, she said.

Some detractors argue that the term “fatty” is sufficiently descriptive and not stigmatizing. However, Dr. Newsome contends that the panel’s research unequivocally disproves this notion.

“Our Delphi process demonstrated very clearly that over 50% felt it was stigmatizing, and in particular, there were clear supportive views for this change from many patient groups,” he noted. “The new nomenclature empowers patients to explain what the condition means without the use of emotional language.”
 

An opportunity to improve care

One compelling way to persuade reluctant adopters of the new nomenclature’s value is to highlight the opportunities it presents.

The updated terminology opens avenues for research and clinical improvements for patients who meet MASLD criteria and consume alcohol at higher levels (MetALD), Dr. Newsome said.

“There are questions about the relative contribution of these two factors to liver injury, and I see this as an opportunity to explore this area further,” he said.

Hepatologists should embrace this change as a means of increasing awareness regarding the metabolic origins of the disease, Dr. Rinella said. This, in turn, will help identify more patients who require treatment but who are currently overlooked by the existing system, she noted.

“Right now, only around 1% of people with advanced disease are being identified by primary care physicians,” she said. “Hopefully, by elevating the role of metabolic disease, primary care physicians, endocrinologists, and gastroenterologists will be able to identify more patients and bring them to care before they develop cirrhosis.”

Such an outcome would signify much more than a mere semantic shift; it would represent a major advancement in the diagnosis and management of the disease.

A version of this article appeared on Medscape.com.

A noteworthy shift recently occurred in the field of hepatology, but it didn’t stem from a clinical trial or medical finding. Instead, the change arose from a matter of semantics.

In a special article published online in the journal Hepatology, a diverse international consensus group introduced new terminology for one of the world’s most rapidly growing diseases.

The term nonalcoholic fatty liver disease (NAFLD) was to be officially retired, replaced with a more precise and descriptive term – metabolic dysfunction–associated steatotic liver disease (MASLD).

In addition, steatotic liver disease (SLD) would be used as an umbrella term encompassing both MASLD and a new subcategory, MetALD, for individuals with MASLD whose alcohol consumption ranges from 140 to 350 g/wk for women and from 210 to 420 g/wk for men. Nonalcoholic steatohepatitis (NASH) would be known as metabolic dysfunction-associated steatohepatitis (MASH).

The new terminology represents small changes with significant implications, especially for patients with MetALD, said the NAFLD nomenclature consensus group’s co-lead, Mary E. Rinella, MD, professor of medicine at University of Chicago and director of the metabolic and fatty liver program at University of Chicago Hospitals.

“The only really new thing we did is identify a group of people who meet criteria for MASLD and also drink more than the allowable limit,” she said. “There are tons of these patients who were not being considered before. Now they’re in a category by themselves, where they are going to be able to be studied and better understood.”
 

Why make a change?

The unveiling of the new nomenclature marked the culmination of 3 years of dedicated work that was built upon decades of growing understanding about the pathophysiologic underpinnings of these disease states.

The terms NAFLD and NASH emerged in 1980 to describe patients with chronic liver disease who denied excessive alcohol consumption. However, in the past 2 decades, it became increasingly evident that the existing terminology was inadequate, the consensus group’s co-lead, Philip Newsome, PhD, said in an interview.

“There was a strong desire for a name that describes what the condition is, rather than what it isn’t; avoiding use of stigmatizing terms, such as fatty and alcoholic; and finally, a nomenclature that could recognize the coexistence of conditions,” said Dr. Newsome, former secretary general of the European Association for the Study of the Liver (EASL), and director of the Centre for Liver and Gastrointestinal Research at the University of Birmingham, England.

These forces, combined with the recognition that NAFLD and alcohol-related liver disease shared biological processes, created momentum for change.

The idea gained traction with a 2020 article that proposed “MAFLD” as a more suitable term because it would link the disease with its known cardiometabolic risks, Dr. Rinella explained.

“We thought that paper was going to be the beginning of a conversation, but what happened instead is it became a full-court press,” Dr. Rinella said.

Dr. Rinella and Dr. Newsome then spearheaded a study to determine whether content experts and patients supported change. The process was led by three prominent international liver societies: EASL, the American Association for the Study of Liver Diseases (AASLD), and the Asociación Latinoamericana para el Estudio del Hígado. The organizations received input from 236 panelists from 56 countries, reflecting the diverse voices essential for addressing a disease with an expanding global prevalence rate.

In this globalized world, you cannot make a decision from on high and then expect everybody to just adopt it, Dr. Rinella noted.

The panel utilized a modified Delphi consensus approach, necessitating a supermajority of respondents (67%) to vote in favor of the changes. Seventy-four percent felt that the current nomenclature was sufficiently flawed to consider a name change, and 89% preferred terminology that describes the underlying cause of the disease. A supermajority felt that having “metabolic disease or dysfunction” in the name would help patients better understand their disease (72%) and help health care professionals better explain or understand the disease (80%).

The participants settled on the new terminology, and the study resulted in a conclusion: “The new nomenclature and diagnostic criteria are widely supported, nonstigmatizing, and can improve awareness and patient identification.”

It was by no means a simple or straightforward task, according to Dr. Rinella. “Anytime you have a contentious issue and you engage a broad range of stakeholders, many of which you know are in disagreement, you’re going to have a difficult time reaching consensus,” she said.
 

Reassuring reluctant adopters

The backing of international liver societies will be crucial to ensuring the smooth and relatively swift adoption of the new nomenclature. The AASLD announced in July that it would begin this process by holding conversations with key stakeholders, including the Food and Drug Administration, patient organizations, and pharmaceutical industry representatives.

“By engaging external groups, we have gained valuable insights into potential roadblocks or barriers that may impede the full implementation of the new MASLD nomenclature,” AASLD President Norah Terrault, MD, MPH, FAASLD, told this news organization. “Knowing the types of issues they face will allow us to build an implementation plan that will help guide the field through adoption.”

Even with buy-in from key stakeholders, implementing the changes will be no small feat. It’s a “vast undertaking” that may result in short-term frustrations for some groups, Dr. Terrault said.

“For instance, researchers whose work commenced under the old nomenclature may not be able to alter their research papers and will need to publish under the old nomenclature, which may impact which journals their research could be published in,” she said. “Some patient advocacy groups may have the old nomenclature in their names, resulting in a need to rebrand and revise their educational resources. Patient materials need to be updated. Primary care professionals need to be educated. The list goes on.”

These changes demand both patience and time, Dr. Terrault said. This applies to those tasked with persuading colleagues and patients, as well as clinicians, many of whom have already expressed some resistance to the updated terminology.

The panel anticipated pushback from clinicians who still advocate for NAFLD. However, Dr. Rinella countered that a diagnosis of MASLD requires only one cardiometabolic risk factor and has 99% overlap in most populations. In contrast, the MAFLD diagnostic criteria put forward in 2020 proposed even more restrictive cardiometabolic criteria and greater tolerance for alcohol consumption and would alter the disease natural history, she said.

Concerns have also been raised that replacing NAFLD with MASLD might complicate the value of prior research efforts. However, this should not be a cause for concern, as extensive examination across multiple populations has demonstrated near complete overlap between the two definitions, Dr. Rinella said. Biomarker development, natural history studies, and drug development research will remain unaffected, she said.

Some detractors argue that the term “fatty” is sufficiently descriptive and not stigmatizing. However, Dr. Newsome contends that the panel’s research unequivocally disproves this notion.

“Our Delphi process demonstrated very clearly that over 50% felt it was stigmatizing, and in particular, there were clear supportive views for this change from many patient groups,” he noted. “The new nomenclature empowers patients to explain what the condition means without the use of emotional language.”
 

An opportunity to improve care

One compelling way to persuade reluctant adopters of the new nomenclature’s value is to highlight the opportunities it presents.

The updated terminology opens avenues for research and clinical improvements for patients who meet MASLD criteria and consume alcohol at higher levels (MetALD), Dr. Newsome said.

“There are questions about the relative contribution of these two factors to liver injury, and I see this as an opportunity to explore this area further,” he said.

Hepatologists should embrace this change as a means of increasing awareness regarding the metabolic origins of the disease, Dr. Rinella said. This, in turn, will help identify more patients who require treatment but who are currently overlooked by the existing system, she noted.

“Right now, only around 1% of people with advanced disease are being identified by primary care physicians,” she said. “Hopefully, by elevating the role of metabolic disease, primary care physicians, endocrinologists, and gastroenterologists will be able to identify more patients and bring them to care before they develop cirrhosis.”

Such an outcome would signify much more than a mere semantic shift; it would represent a major advancement in the diagnosis and management of the disease.

A version of this article appeared on Medscape.com.

Multicancer early-detection blood (MCED) tests are the focus of intensive development. What techniques do these tests use? What potential do they show? Suzette Delaloge, MD, MSc, oncologist, breast cancer specialist, and director of the individualized cancer prevention program (Interception) at the Gustave Roussy Institute in Villejuif, France, looks into these “liquid biopsies” and shares her reservations about their potential marketing, especially to the organized care plans.

Question: What are the general principles underpinning these MCED tests?

Suzette Delaloge, MD, MSc: Despite their specificities, the general idea is to detect certain cancer markers in various body fluids (blood, urine, saliva, etc.), for example, molecules released by cancer cells (cytokines, inflammatory proteins, leptin, etc.) or distinctive features of the DNA in tumor cells. In blood, these molecules can be found in plasma or in serum. In urine, it’s more about detecting kidney, bladder, and urinary tract cancers.

Q: What sort of time frame are we looking at for these MCED tests to be used in routine practice?

Dr. Delaloge: They first appeared around 10 years ago. Development of these tests has intensified in recent years. There are numerous research laboratories, both public and private, that are developing different early-detection tests for cancer.

Some of these development processes are about to come to an end and are expected to be in regular, concrete use within 5-10 years. For the most advanced developments, the main biologic material researched and analyzed is DNA from cancer cells. We all have fragments of DNA from dead cells in our plasma (apoptosis), but cancer cells release more of these than others, and most importantly, their DNA has distinctive characteristics. The idea is to develop tests capable of detecting these characteristics.

Liquid biopsies based on genomic biomarkers could make MCED a reality, especially for cancers for which there is no standard screening process. But at this stage of the research, there are limitations, including low sensitivity for detecting stage I cancers in validation studies and an increased risk for overdiagnosis.

Q: What specific set of characteristics are the most advanced approaches based on?

Dr. Delaloge: They’re based on the analysis of DNA methylation, a biological process by which CH3 methyl groups are added to the DNA molecule and that determines gene expression. This phenomenon differs depending on whether the cell is cancerous. Among the tests currently under development making use of this specific characteristic is the Galleri test, which is the most advanced of them all.

A previous British National Health Service study, SYMPLIFY, which was published in 2023 by researchers at the University of Oxford, was conducted in symptomatic patients attending a health center. It offers promising results in a diagnostic situation. It has nothing at all to do with screening here. A large, randomized English study, NHS-Galleri, is underway, this time involving the general population, with the aim of assessing the potential benefit of the same test as screening in 140,000 people between ages 50 and 77 years.

In the SYMPLIFY study, which was carried out in symptomatic patients attending a health center, the Galleri MCED test had a positive predictive value of 75.5%, a negative predictive value of 97.6%, a sensitivity of 66.3%, and a specificity of 98.4%. Sensitivity increased with age and cancer stage from 24.2% at stage I to 95.3% at stage IV. For cases for which a cancer signal was detected in patients with cancer, the prediction of the original site of the cancer by the MCED test was accurate in 85.2% of cases. This large-scale prospective evaluation of an MCED diagnostic test confirms its feasibility in a symptomatic population but is not yet sufficiently accurate to “confirm or rule out the presence of cancer.” According to the authors, “in cases in which the MCED test detects a cancer signal in this context, the probability of a diagnosis of cancer being made is considerably higher and may identify cancers at sites other than those suspected during the initial referral phase, thus reducing delays in diagnosis.” A negative test means a lower likelihood of cancer but not so low that proper investigation can be ruled out. Further tests will be needed to optimize use of a negative predictive value.

Q: Does MCED testing concern all types of cancer?

Dr. Delaloge: The Galleri test is based on full profiling of DNA methylation. This allows for early diagnosis of cancer even before it can be seen on imaging tests. The issue with these tests is that they aren’t that good at early diagnosis of the most common types of cancer (breast, colorectal, cervical, etc.) for which we already have more efficient means such as the fecal immunochemical test for colorectal cancer, mammography, HPV testing, and so on.

These blood tests would thus not be aimed at replacing routine screening but rather at screening asymptomatic individuals or those with nonspecific signs for cancers for which we have few or no screening measures and which are on the rise, such as deep tumors and cancer diagnosed at a late stage, namely pancreas, bile duct, ovarian, esophageal, lung, stomach, etc.

The results from the studies published are promising, but others are underway to confirm the benefit of these MCEDs. The challenge is to identify cancer at an early stage, at a stage where it will be easier to cure the patient and control its growth using treatments that are less onerous for the patient and that have fewer aftereffects but not at the expense of a massive increase in overdiagnosis, as seen with prostate-specific antigen levels in prostate cancer a few years ago!

Q: What would be the focus of these MCED tests?

Dr. Delaloge: We must be alert to the risk for the market development of MCED tests. For now, they are mostly, especially the Galleri test, developed in the general population to screen for types of cancer that could not be detected in any other way but also because it’s the most financially beneficial situation. The designers want to position themselves in the general population, regardless of whether this means they’ll have to test hundreds of people to find one for whom the test is beneficial. What’s more, developing tests in isolation, without considering their place in ad hoc treatment pathways, is not realistic. It’s likely that some of these tests will be marketed within the next 10 years, but the health care systems destined to receive them are not remotely ready to do so.

Q: An even more recent publication, from late July 2023, is even more exciting in relation to early detection of lung cancer using circulating DNA sequencing. What are your thoughts on it?

Dr. Delaloge: Initially overtaken by other technologies in favor of MCED approaches, DNA sequencing as a technique to detect somatic mutations seems to have reentered the competition with this new-generation research. The authors published some very interesting results, especially for stage I lung cancer with a very high sensitivity of 75%. [Editor’s note: A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected more than 90% of patients with lung cancer, including those with stage I and II disease.]

This research illustrates the difficulty of providing high performance while covering a broad range of cancers. Here, the good results mainly concern lung cancer. Researchers and health care authorities must be alert to ensuring that MCED tests prove themselves in terms of sensitivity and specificity in responding to a medical need and in their impact on specific mortality. This craze for MCED tests must not hinder the development of “single-cancer” technologies that may be much better for detecting specific cancers. This recent publication is interesting in this respect, because this sequencing test seems to be particularly good at detecting lung cancer.

Q: Another approach used in MCED tests is based on analyzing the size of DNA fragments in the blood. Can you explain how this works?

Dr. Delaloge: When cancer is not present, the size of DNA fragments in cells is much more homogeneous. Here also, the benefit of MCED based on this technique rests on the very early detection of cancers that are less common than those for which we already have good screening methods available.

Other approaches, still at the experimental stage, detect certain proteins, certain inflammatory molecules, RNA, etc. But for many researchers, the future will involve pairing tests on the basis of circulating DNA in the blood with the detection of specific molecules indicating the presence of cancer to obtain early screening tests that are even more effective or that possibly even allow us to identify an appropriate treatment at an early stage.

The development of a simple test based on a blood draw that allows us to screen early for all cancers and that would replace all current screening measures is, therefore, not imminent, although it could potentially be on the horizon in years to come. Alongside this, an important issue is the benefit of cancer screening in the general population vs. in a targeted population with a specific risk. The latter option is in development but requires an individualized screening pathway based on blood testing and current screening methods: imaging, etc. It also depends on an individual’s cancer risk profile such as age, personal and family medical history, genetic predisposition, and so on.

According to recent modeling, these multicancer tests could theoretically prevent a minimum of 2,000 deaths from cancer per 100,000 people between ages 50 and 79 years screened per year (17% fewer deaths from cancer per year).

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

Multicancer early-detection blood (MCED) tests are the focus of intensive development. What techniques do these tests use? What potential do they show? Suzette Delaloge, MD, MSc, oncologist, breast cancer specialist, and director of the individualized cancer prevention program (Interception) at the Gustave Roussy Institute in Villejuif, France, looks into these “liquid biopsies” and shares her reservations about their potential marketing, especially to the organized care plans.

Question: What are the general principles underpinning these MCED tests?

Suzette Delaloge, MD, MSc: Despite their specificities, the general idea is to detect certain cancer markers in various body fluids (blood, urine, saliva, etc.), for example, molecules released by cancer cells (cytokines, inflammatory proteins, leptin, etc.) or distinctive features of the DNA in tumor cells. In blood, these molecules can be found in plasma or in serum. In urine, it’s more about detecting kidney, bladder, and urinary tract cancers.

Q: What sort of time frame are we looking at for these MCED tests to be used in routine practice?

Dr. Delaloge: They first appeared around 10 years ago. Development of these tests has intensified in recent years. There are numerous research laboratories, both public and private, that are developing different early-detection tests for cancer.

Some of these development processes are about to come to an end and are expected to be in regular, concrete use within 5-10 years. For the most advanced developments, the main biologic material researched and analyzed is DNA from cancer cells. We all have fragments of DNA from dead cells in our plasma (apoptosis), but cancer cells release more of these than others, and most importantly, their DNA has distinctive characteristics. The idea is to develop tests capable of detecting these characteristics.

Liquid biopsies based on genomic biomarkers could make MCED a reality, especially for cancers for which there is no standard screening process. But at this stage of the research, there are limitations, including low sensitivity for detecting stage I cancers in validation studies and an increased risk for overdiagnosis.

Q: What specific set of characteristics are the most advanced approaches based on?

Dr. Delaloge: They’re based on the analysis of DNA methylation, a biological process by which CH3 methyl groups are added to the DNA molecule and that determines gene expression. This phenomenon differs depending on whether the cell is cancerous. Among the tests currently under development making use of this specific characteristic is the Galleri test, which is the most advanced of them all.

A previous British National Health Service study, SYMPLIFY, which was published in 2023 by researchers at the University of Oxford, was conducted in symptomatic patients attending a health center. It offers promising results in a diagnostic situation. It has nothing at all to do with screening here. A large, randomized English study, NHS-Galleri, is underway, this time involving the general population, with the aim of assessing the potential benefit of the same test as screening in 140,000 people between ages 50 and 77 years.

In the SYMPLIFY study, which was carried out in symptomatic patients attending a health center, the Galleri MCED test had a positive predictive value of 75.5%, a negative predictive value of 97.6%, a sensitivity of 66.3%, and a specificity of 98.4%. Sensitivity increased with age and cancer stage from 24.2% at stage I to 95.3% at stage IV. For cases for which a cancer signal was detected in patients with cancer, the prediction of the original site of the cancer by the MCED test was accurate in 85.2% of cases. This large-scale prospective evaluation of an MCED diagnostic test confirms its feasibility in a symptomatic population but is not yet sufficiently accurate to “confirm or rule out the presence of cancer.” According to the authors, “in cases in which the MCED test detects a cancer signal in this context, the probability of a diagnosis of cancer being made is considerably higher and may identify cancers at sites other than those suspected during the initial referral phase, thus reducing delays in diagnosis.” A negative test means a lower likelihood of cancer but not so low that proper investigation can be ruled out. Further tests will be needed to optimize use of a negative predictive value.

Q: Does MCED testing concern all types of cancer?

Dr. Delaloge: The Galleri test is based on full profiling of DNA methylation. This allows for early diagnosis of cancer even before it can be seen on imaging tests. The issue with these tests is that they aren’t that good at early diagnosis of the most common types of cancer (breast, colorectal, cervical, etc.) for which we already have more efficient means such as the fecal immunochemical test for colorectal cancer, mammography, HPV testing, and so on.

These blood tests would thus not be aimed at replacing routine screening but rather at screening asymptomatic individuals or those with nonspecific signs for cancers for which we have few or no screening measures and which are on the rise, such as deep tumors and cancer diagnosed at a late stage, namely pancreas, bile duct, ovarian, esophageal, lung, stomach, etc.

The results from the studies published are promising, but others are underway to confirm the benefit of these MCEDs. The challenge is to identify cancer at an early stage, at a stage where it will be easier to cure the patient and control its growth using treatments that are less onerous for the patient and that have fewer aftereffects but not at the expense of a massive increase in overdiagnosis, as seen with prostate-specific antigen levels in prostate cancer a few years ago!

Q: What would be the focus of these MCED tests?

Dr. Delaloge: We must be alert to the risk for the market development of MCED tests. For now, they are mostly, especially the Galleri test, developed in the general population to screen for types of cancer that could not be detected in any other way but also because it’s the most financially beneficial situation. The designers want to position themselves in the general population, regardless of whether this means they’ll have to test hundreds of people to find one for whom the test is beneficial. What’s more, developing tests in isolation, without considering their place in ad hoc treatment pathways, is not realistic. It’s likely that some of these tests will be marketed within the next 10 years, but the health care systems destined to receive them are not remotely ready to do so.

Q: An even more recent publication, from late July 2023, is even more exciting in relation to early detection of lung cancer using circulating DNA sequencing. What are your thoughts on it?

Dr. Delaloge: Initially overtaken by other technologies in favor of MCED approaches, DNA sequencing as a technique to detect somatic mutations seems to have reentered the competition with this new-generation research. The authors published some very interesting results, especially for stage I lung cancer with a very high sensitivity of 75%. [Editor’s note: A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected more than 90% of patients with lung cancer, including those with stage I and II disease.]

This research illustrates the difficulty of providing high performance while covering a broad range of cancers. Here, the good results mainly concern lung cancer. Researchers and health care authorities must be alert to ensuring that MCED tests prove themselves in terms of sensitivity and specificity in responding to a medical need and in their impact on specific mortality. This craze for MCED tests must not hinder the development of “single-cancer” technologies that may be much better for detecting specific cancers. This recent publication is interesting in this respect, because this sequencing test seems to be particularly good at detecting lung cancer.

Q: Another approach used in MCED tests is based on analyzing the size of DNA fragments in the blood. Can you explain how this works?

Dr. Delaloge: When cancer is not present, the size of DNA fragments in cells is much more homogeneous. Here also, the benefit of MCED based on this technique rests on the very early detection of cancers that are less common than those for which we already have good screening methods available.

Other approaches, still at the experimental stage, detect certain proteins, certain inflammatory molecules, RNA, etc. But for many researchers, the future will involve pairing tests on the basis of circulating DNA in the blood with the detection of specific molecules indicating the presence of cancer to obtain early screening tests that are even more effective or that possibly even allow us to identify an appropriate treatment at an early stage.

The development of a simple test based on a blood draw that allows us to screen early for all cancers and that would replace all current screening measures is, therefore, not imminent, although it could potentially be on the horizon in years to come. Alongside this, an important issue is the benefit of cancer screening in the general population vs. in a targeted population with a specific risk. The latter option is in development but requires an individualized screening pathway based on blood testing and current screening methods: imaging, etc. It also depends on an individual’s cancer risk profile such as age, personal and family medical history, genetic predisposition, and so on.

According to recent modeling, these multicancer tests could theoretically prevent a minimum of 2,000 deaths from cancer per 100,000 people between ages 50 and 79 years screened per year (17% fewer deaths from cancer per year).

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

Multicancer early-detection blood (MCED) tests are the focus of intensive development. What techniques do these tests use? What potential do they show? Suzette Delaloge, MD, MSc, oncologist, breast cancer specialist, and director of the individualized cancer prevention program (Interception) at the Gustave Roussy Institute in Villejuif, France, looks into these “liquid biopsies” and shares her reservations about their potential marketing, especially to the organized care plans.

Question: What are the general principles underpinning these MCED tests?

Suzette Delaloge, MD, MSc: Despite their specificities, the general idea is to detect certain cancer markers in various body fluids (blood, urine, saliva, etc.), for example, molecules released by cancer cells (cytokines, inflammatory proteins, leptin, etc.) or distinctive features of the DNA in tumor cells. In blood, these molecules can be found in plasma or in serum. In urine, it’s more about detecting kidney, bladder, and urinary tract cancers.

Q: What sort of time frame are we looking at for these MCED tests to be used in routine practice?

Dr. Delaloge: They first appeared around 10 years ago. Development of these tests has intensified in recent years. There are numerous research laboratories, both public and private, that are developing different early-detection tests for cancer.

Some of these development processes are about to come to an end and are expected to be in regular, concrete use within 5-10 years. For the most advanced developments, the main biologic material researched and analyzed is DNA from cancer cells. We all have fragments of DNA from dead cells in our plasma (apoptosis), but cancer cells release more of these than others, and most importantly, their DNA has distinctive characteristics. The idea is to develop tests capable of detecting these characteristics.

Liquid biopsies based on genomic biomarkers could make MCED a reality, especially for cancers for which there is no standard screening process. But at this stage of the research, there are limitations, including low sensitivity for detecting stage I cancers in validation studies and an increased risk for overdiagnosis.

Q: What specific set of characteristics are the most advanced approaches based on?

Dr. Delaloge: They’re based on the analysis of DNA methylation, a biological process by which CH3 methyl groups are added to the DNA molecule and that determines gene expression. This phenomenon differs depending on whether the cell is cancerous. Among the tests currently under development making use of this specific characteristic is the Galleri test, which is the most advanced of them all.

A previous British National Health Service study, SYMPLIFY, which was published in 2023 by researchers at the University of Oxford, was conducted in symptomatic patients attending a health center. It offers promising results in a diagnostic situation. It has nothing at all to do with screening here. A large, randomized English study, NHS-Galleri, is underway, this time involving the general population, with the aim of assessing the potential benefit of the same test as screening in 140,000 people between ages 50 and 77 years.

In the SYMPLIFY study, which was carried out in symptomatic patients attending a health center, the Galleri MCED test had a positive predictive value of 75.5%, a negative predictive value of 97.6%, a sensitivity of 66.3%, and a specificity of 98.4%. Sensitivity increased with age and cancer stage from 24.2% at stage I to 95.3% at stage IV. For cases for which a cancer signal was detected in patients with cancer, the prediction of the original site of the cancer by the MCED test was accurate in 85.2% of cases. This large-scale prospective evaluation of an MCED diagnostic test confirms its feasibility in a symptomatic population but is not yet sufficiently accurate to “confirm or rule out the presence of cancer.” According to the authors, “in cases in which the MCED test detects a cancer signal in this context, the probability of a diagnosis of cancer being made is considerably higher and may identify cancers at sites other than those suspected during the initial referral phase, thus reducing delays in diagnosis.” A negative test means a lower likelihood of cancer but not so low that proper investigation can be ruled out. Further tests will be needed to optimize use of a negative predictive value.

Q: Does MCED testing concern all types of cancer?

Dr. Delaloge: The Galleri test is based on full profiling of DNA methylation. This allows for early diagnosis of cancer even before it can be seen on imaging tests. The issue with these tests is that they aren’t that good at early diagnosis of the most common types of cancer (breast, colorectal, cervical, etc.) for which we already have more efficient means such as the fecal immunochemical test for colorectal cancer, mammography, HPV testing, and so on.

These blood tests would thus not be aimed at replacing routine screening but rather at screening asymptomatic individuals or those with nonspecific signs for cancers for which we have few or no screening measures and which are on the rise, such as deep tumors and cancer diagnosed at a late stage, namely pancreas, bile duct, ovarian, esophageal, lung, stomach, etc.

The results from the studies published are promising, but others are underway to confirm the benefit of these MCEDs. The challenge is to identify cancer at an early stage, at a stage where it will be easier to cure the patient and control its growth using treatments that are less onerous for the patient and that have fewer aftereffects but not at the expense of a massive increase in overdiagnosis, as seen with prostate-specific antigen levels in prostate cancer a few years ago!

Q: What would be the focus of these MCED tests?

Dr. Delaloge: We must be alert to the risk for the market development of MCED tests. For now, they are mostly, especially the Galleri test, developed in the general population to screen for types of cancer that could not be detected in any other way but also because it’s the most financially beneficial situation. The designers want to position themselves in the general population, regardless of whether this means they’ll have to test hundreds of people to find one for whom the test is beneficial. What’s more, developing tests in isolation, without considering their place in ad hoc treatment pathways, is not realistic. It’s likely that some of these tests will be marketed within the next 10 years, but the health care systems destined to receive them are not remotely ready to do so.

Q: An even more recent publication, from late July 2023, is even more exciting in relation to early detection of lung cancer using circulating DNA sequencing. What are your thoughts on it?

Dr. Delaloge: Initially overtaken by other technologies in favor of MCED approaches, DNA sequencing as a technique to detect somatic mutations seems to have reentered the competition with this new-generation research. The authors published some very interesting results, especially for stage I lung cancer with a very high sensitivity of 75%. [Editor’s note: A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected more than 90% of patients with lung cancer, including those with stage I and II disease.]

This research illustrates the difficulty of providing high performance while covering a broad range of cancers. Here, the good results mainly concern lung cancer. Researchers and health care authorities must be alert to ensuring that MCED tests prove themselves in terms of sensitivity and specificity in responding to a medical need and in their impact on specific mortality. This craze for MCED tests must not hinder the development of “single-cancer” technologies that may be much better for detecting specific cancers. This recent publication is interesting in this respect, because this sequencing test seems to be particularly good at detecting lung cancer.

Q: Another approach used in MCED tests is based on analyzing the size of DNA fragments in the blood. Can you explain how this works?

Dr. Delaloge: When cancer is not present, the size of DNA fragments in cells is much more homogeneous. Here also, the benefit of MCED based on this technique rests on the very early detection of cancers that are less common than those for which we already have good screening methods available.

Other approaches, still at the experimental stage, detect certain proteins, certain inflammatory molecules, RNA, etc. But for many researchers, the future will involve pairing tests on the basis of circulating DNA in the blood with the detection of specific molecules indicating the presence of cancer to obtain early screening tests that are even more effective or that possibly even allow us to identify an appropriate treatment at an early stage.

The development of a simple test based on a blood draw that allows us to screen early for all cancers and that would replace all current screening measures is, therefore, not imminent, although it could potentially be on the horizon in years to come. Alongside this, an important issue is the benefit of cancer screening in the general population vs. in a targeted population with a specific risk. The latter option is in development but requires an individualized screening pathway based on blood testing and current screening methods: imaging, etc. It also depends on an individual’s cancer risk profile such as age, personal and family medical history, genetic predisposition, and so on.

According to recent modeling, these multicancer tests could theoretically prevent a minimum of 2,000 deaths from cancer per 100,000 people between ages 50 and 79 years screened per year (17% fewer deaths from cancer per year).

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

With physicians under increasing pressure to see more patients in shorter office visits, developing a social media presence may offer valuable opportunities to connect with patients, explain procedures, combat misinformation, talk through a published article, and even share a joke or meme.

But there are caveats for doctors posting on social media platforms. This news organization spoke to four doctors who successfully use social media. Here is what they want you to know before you post – and how to make your posts personable and helpful to patients and your practice simultaneously.
 

Use social media for the right reasons

While you’re under no obligation to build a social media presence, if you’re going to do it, be sure your intentions are solid, said Don S. Dizon, MD, professor of medicine and professor of surgery at Brown University, Providence, R.I. Dr. Dizon, as @DoctorDon, has 44,700 TikTok followers and uses the platform to answer cancer-related questions.

“It should be your altruism that motivates you to post,” said Dr. Dizon, who is also associate director of community outreach and engagement at the Legorreta Cancer Center in Providence, R.I., and director of medical oncology at Rhode Island Hospital. “What we can do for society at large is to provide our input into issues, add informed opinions where there’s controversy, and address misinformation.”

If you don’t know where to start, consider seeking a digital mentor to talk through your options.

“You may never meet this person, but you should choose them if you like their style, their content, their delivery, and their perspective,” Dr. Dizon said. “Find another doctor out there on social media whom you feel you can emulate. Take your time, too. Soon enough, you’ll develop your own style and your own online persona.”
 

Post clear, accurate information

If you want to be lighthearted on social media, that’s your choice. But Jennifer Trachtenberg, a pediatrician with nearly 7,000 Instagram followers in New York who posts as @askdrjen, prefers to offer vaccine scheduling tips, alert parents about COVID-19 rates, and offer advice on cold and flu prevention.

“Right now, I’m mainly doing this to educate patients and make them aware of topics that I think are important and that I see my patients needing more information on,” she said. “We have to be clear: People take what we say seriously. So, while it’s important to be relatable, it’s even more important to share evidence-based information.”
 

Many patients get their information on social media

While patients once came to the doctor armed with information sourced via “Doctor Google,” today, just as many patients use social media to learn about their condition or the medications they’re taking.

Unfortunately, a recent Ohio State University, Columbus, study found that the majority of gynecologic cancer advice on TikTok, for example, was either misleading or inaccurate.

“This misinformation should be a motivator for physicians to explore the social media space,” Dr. Dizon said. “Our voices need to be on there.”
 

Break down barriers – and make connections

Mike Natter, MD, an endocrinologist in New York, has type 1 diabetes. This informs his work – and his life – and he’s passionate about sharing it with his 117,000 followers as @mike.natter on Instagram.

“A lot of type 1s follow me, so there’s an advocacy component to what I do,” he said. “I enjoy being able to raise awareness and keep people up to date on the newest research and treatment.”

But that’s not all: Dr. Natter is also an artist who went to art school before he went to medical school, and his account is rife with his cartoons and illustrations about everything from valvular disease to diabetic ketoacidosis.

“I found that I was drawing a lot of my notes in medical school,” he said. “When I drew my notes, I did quite well, and I think that using art and illustration is a great tool. It breaks down barriers and makes health information all the more accessible to everyone.”
 

Share your expertise as a doctor – and a person

As a mom and pediatrician, Krupa Playforth, MD, who practices in Vienna, Va., knows that what she posts carries weight. So, whether she’s writing about backpack safety tips, choking hazards, or separation anxiety, her followers can rest assured that she’s posting responsibly.

“Pediatricians often underestimate how smart parents are,” said Dr. Playforth, who has three kids, ages 8, 5, and 2, and has 137,000 followers on @thepediatricianmom, her Instagram account. “Their anxiety comes from an understandable place, which is why I see my role as that of a parent and pediatrician who can translate the knowledge pediatricians have into something parents can understand.”

Dr. Playforth, who jumped on social media during COVID-19 and experienced a positive response in her local community, said being on social media is imperative if you’re a pediatrician.

“This is the future of pediatric medicine in particular,” she said. “A lot of pediatricians don’t want to embrace social media, but I think that’s a mistake. After all, while parents think pediatricians have all the answers, when we think of our own children, most doctors are like other parents – we can’t think objectively about our kids. It’s helpful for me to share that and to help parents feel less alone.”

If you’re not yet using social media to the best of your physician abilities, you might take a shot at becoming widely recognizable. Pick a preferred platform, answer common patient questions, dispel medical myths, provide pertinent information, and let your personality shine.

A version of this article first appeared on Medscape.com.

With physicians under increasing pressure to see more patients in shorter office visits, developing a social media presence may offer valuable opportunities to connect with patients, explain procedures, combat misinformation, talk through a published article, and even share a joke or meme.

But there are caveats for doctors posting on social media platforms. This news organization spoke to four doctors who successfully use social media. Here is what they want you to know before you post – and how to make your posts personable and helpful to patients and your practice simultaneously.
 

Use social media for the right reasons

While you’re under no obligation to build a social media presence, if you’re going to do it, be sure your intentions are solid, said Don S. Dizon, MD, professor of medicine and professor of surgery at Brown University, Providence, R.I. Dr. Dizon, as @DoctorDon, has 44,700 TikTok followers and uses the platform to answer cancer-related questions.

“It should be your altruism that motivates you to post,” said Dr. Dizon, who is also associate director of community outreach and engagement at the Legorreta Cancer Center in Providence, R.I., and director of medical oncology at Rhode Island Hospital. “What we can do for society at large is to provide our input into issues, add informed opinions where there’s controversy, and address misinformation.”

If you don’t know where to start, consider seeking a digital mentor to talk through your options.

“You may never meet this person, but you should choose them if you like their style, their content, their delivery, and their perspective,” Dr. Dizon said. “Find another doctor out there on social media whom you feel you can emulate. Take your time, too. Soon enough, you’ll develop your own style and your own online persona.”
 

Post clear, accurate information

If you want to be lighthearted on social media, that’s your choice. But Jennifer Trachtenberg, a pediatrician with nearly 7,000 Instagram followers in New York who posts as @askdrjen, prefers to offer vaccine scheduling tips, alert parents about COVID-19 rates, and offer advice on cold and flu prevention.

“Right now, I’m mainly doing this to educate patients and make them aware of topics that I think are important and that I see my patients needing more information on,” she said. “We have to be clear: People take what we say seriously. So, while it’s important to be relatable, it’s even more important to share evidence-based information.”
 

Many patients get their information on social media

While patients once came to the doctor armed with information sourced via “Doctor Google,” today, just as many patients use social media to learn about their condition or the medications they’re taking.

Unfortunately, a recent Ohio State University, Columbus, study found that the majority of gynecologic cancer advice on TikTok, for example, was either misleading or inaccurate.

“This misinformation should be a motivator for physicians to explore the social media space,” Dr. Dizon said. “Our voices need to be on there.”
 

Break down barriers – and make connections

Mike Natter, MD, an endocrinologist in New York, has type 1 diabetes. This informs his work – and his life – and he’s passionate about sharing it with his 117,000 followers as @mike.natter on Instagram.

“A lot of type 1s follow me, so there’s an advocacy component to what I do,” he said. “I enjoy being able to raise awareness and keep people up to date on the newest research and treatment.”

But that’s not all: Dr. Natter is also an artist who went to art school before he went to medical school, and his account is rife with his cartoons and illustrations about everything from valvular disease to diabetic ketoacidosis.

“I found that I was drawing a lot of my notes in medical school,” he said. “When I drew my notes, I did quite well, and I think that using art and illustration is a great tool. It breaks down barriers and makes health information all the more accessible to everyone.”
 

Share your expertise as a doctor – and a person

As a mom and pediatrician, Krupa Playforth, MD, who practices in Vienna, Va., knows that what she posts carries weight. So, whether she’s writing about backpack safety tips, choking hazards, or separation anxiety, her followers can rest assured that she’s posting responsibly.

“Pediatricians often underestimate how smart parents are,” said Dr. Playforth, who has three kids, ages 8, 5, and 2, and has 137,000 followers on @thepediatricianmom, her Instagram account. “Their anxiety comes from an understandable place, which is why I see my role as that of a parent and pediatrician who can translate the knowledge pediatricians have into something parents can understand.”

Dr. Playforth, who jumped on social media during COVID-19 and experienced a positive response in her local community, said being on social media is imperative if you’re a pediatrician.

“This is the future of pediatric medicine in particular,” she said. “A lot of pediatricians don’t want to embrace social media, but I think that’s a mistake. After all, while parents think pediatricians have all the answers, when we think of our own children, most doctors are like other parents – we can’t think objectively about our kids. It’s helpful for me to share that and to help parents feel less alone.”

If you’re not yet using social media to the best of your physician abilities, you might take a shot at becoming widely recognizable. Pick a preferred platform, answer common patient questions, dispel medical myths, provide pertinent information, and let your personality shine.

A version of this article first appeared on Medscape.com.

With physicians under increasing pressure to see more patients in shorter office visits, developing a social media presence may offer valuable opportunities to connect with patients, explain procedures, combat misinformation, talk through a published article, and even share a joke or meme.

But there are caveats for doctors posting on social media platforms. This news organization spoke to four doctors who successfully use social media. Here is what they want you to know before you post – and how to make your posts personable and helpful to patients and your practice simultaneously.
 

Use social media for the right reasons

While you’re under no obligation to build a social media presence, if you’re going to do it, be sure your intentions are solid, said Don S. Dizon, MD, professor of medicine and professor of surgery at Brown University, Providence, R.I. Dr. Dizon, as @DoctorDon, has 44,700 TikTok followers and uses the platform to answer cancer-related questions.

“It should be your altruism that motivates you to post,” said Dr. Dizon, who is also associate director of community outreach and engagement at the Legorreta Cancer Center in Providence, R.I., and director of medical oncology at Rhode Island Hospital. “What we can do for society at large is to provide our input into issues, add informed opinions where there’s controversy, and address misinformation.”

If you don’t know where to start, consider seeking a digital mentor to talk through your options.

“You may never meet this person, but you should choose them if you like their style, their content, their delivery, and their perspective,” Dr. Dizon said. “Find another doctor out there on social media whom you feel you can emulate. Take your time, too. Soon enough, you’ll develop your own style and your own online persona.”
 

Post clear, accurate information

If you want to be lighthearted on social media, that’s your choice. But Jennifer Trachtenberg, a pediatrician with nearly 7,000 Instagram followers in New York who posts as @askdrjen, prefers to offer vaccine scheduling tips, alert parents about COVID-19 rates, and offer advice on cold and flu prevention.

“Right now, I’m mainly doing this to educate patients and make them aware of topics that I think are important and that I see my patients needing more information on,” she said. “We have to be clear: People take what we say seriously. So, while it’s important to be relatable, it’s even more important to share evidence-based information.”
 

Many patients get their information on social media

While patients once came to the doctor armed with information sourced via “Doctor Google,” today, just as many patients use social media to learn about their condition or the medications they’re taking.

Unfortunately, a recent Ohio State University, Columbus, study found that the majority of gynecologic cancer advice on TikTok, for example, was either misleading or inaccurate.

“This misinformation should be a motivator for physicians to explore the social media space,” Dr. Dizon said. “Our voices need to be on there.”
 

Break down barriers – and make connections

Mike Natter, MD, an endocrinologist in New York, has type 1 diabetes. This informs his work – and his life – and he’s passionate about sharing it with his 117,000 followers as @mike.natter on Instagram.

“A lot of type 1s follow me, so there’s an advocacy component to what I do,” he said. “I enjoy being able to raise awareness and keep people up to date on the newest research and treatment.”

But that’s not all: Dr. Natter is also an artist who went to art school before he went to medical school, and his account is rife with his cartoons and illustrations about everything from valvular disease to diabetic ketoacidosis.

“I found that I was drawing a lot of my notes in medical school,” he said. “When I drew my notes, I did quite well, and I think that using art and illustration is a great tool. It breaks down barriers and makes health information all the more accessible to everyone.”
 

Share your expertise as a doctor – and a person

As a mom and pediatrician, Krupa Playforth, MD, who practices in Vienna, Va., knows that what she posts carries weight. So, whether she’s writing about backpack safety tips, choking hazards, or separation anxiety, her followers can rest assured that she’s posting responsibly.

“Pediatricians often underestimate how smart parents are,” said Dr. Playforth, who has three kids, ages 8, 5, and 2, and has 137,000 followers on @thepediatricianmom, her Instagram account. “Their anxiety comes from an understandable place, which is why I see my role as that of a parent and pediatrician who can translate the knowledge pediatricians have into something parents can understand.”

Dr. Playforth, who jumped on social media during COVID-19 and experienced a positive response in her local community, said being on social media is imperative if you’re a pediatrician.

“This is the future of pediatric medicine in particular,” she said. “A lot of pediatricians don’t want to embrace social media, but I think that’s a mistake. After all, while parents think pediatricians have all the answers, when we think of our own children, most doctors are like other parents – we can’t think objectively about our kids. It’s helpful for me to share that and to help parents feel less alone.”

If you’re not yet using social media to the best of your physician abilities, you might take a shot at becoming widely recognizable. Pick a preferred platform, answer common patient questions, dispel medical myths, provide pertinent information, and let your personality shine.

A version of this article first appeared on Medscape.com.