Pharmacology

LISBON – Two-thirds of antibiotic prescriptions written for Black patients and more than half of antibiotic prescriptions for Hispanic/Latinx patients are inappropriate, according to data from a study of antibiotic prescribing habits in U.S. doctors’ offices, hospital clinics, and emergency departments.

Eric Young, PharmD, PhD, from the University of Texas at Austin, and UT Health, San Antonio, presented his work as a poster at the 32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022.

“We were really surprised mainly by the racial findings, because Black patients have the highest overall and the highest inappropriate prescribing of antibiotics,” he told this news organization. “There was also a difference seen for age [across all ethnicities].”

Pediatric patients were found to have high overall prescribing but, notably, the lowest inappropriate prescribing among all the patient groups, reported Dr. Young. “This is interesting because oftentimes we think the more antibiotics are prescribed, then surely the greater the inappropriate prescribing would be too, but pediatricians actually have one of the lowest rates of inappropriate antibiotic prescribing. They do a great job.”

The study included more than 7 billion patient visits, 11.3% of which involved an antibiotic prescription.

The rate of antibiotic prescribing was 122 per 1,000 visits in Black patients and 139 per 1,000 visits in Hispanic patients, while in White patients, the rate was 109 per 1,000 visits. The rate was 114 per 1,000 visits in patients younger than 18 years and 170 per 1,000 visits in females.

Dr. Young found that almost 64% of antibiotic prescriptions written for Black patients and 58% for Hispanic patients were inappropriate. For White patients, the rate of inappropriate antibiotic prescribing was 56%. Similarly, 74% of prescriptions dispensed to patients aged 65 years and older and 58% to males were deemed inappropriate.

Kajal Bhakta, PharmD, BCACP, ambulatory care clinical pharmacist, University Health System, UT Health Science Center San Antonio, who was not involved in the study, pointed out that antibiotics are frequently prescribed without confirmation of an infection, owing to the fact that the verification process may delay care, especially in the outpatient setting.

Dr. Bhakta said that overprescribing in the elderly population and in certain ethnic groups was “likely due to socioeconomic and cultural factors. These prescribing methods may lead to unnecessary drug side effects and/or antimicrobial resistance.”

Regarding the patient-doctor consultation process, she pointed out that “older patients may have trouble describing their symptoms, and when those symptoms remain unresolved, providers may be more inclined to prescribe antibiotics to help.”

Sometimes overprescribing can occur because of the logistics involved in getting to the doctor’s office in the outpatient setting. “Sometimes patients struggle with transportation, as two separate trips to the doctor and pharmacy may not be feasible. Additionally, these same patients may have limited access to health care and therefore may use an urgent care facility for their acute infection–like symptoms,” Dr. Bhakta explained.

Dr. Young, who is of Asian descent, first became interested in disparities in health care when he noticed that ethnic minority groups showed greater hesitancy toward COVID-19 vaccination. “I noticed that there weren’t many Asians involved in previous trials and realized at this point that disparities were rampant.”

Dr. Young had been involved in investigating the overall use and the inappropriate use of antibiotics across the whole U.S. population when his interest in health disparities prompted him to study these patterns in specific demographic groups.

“Most previous data are derived from inpatient studies where the physician is giving the antibiotics,” said Dr. Young, who looked specifically at outpatient prescribing.

Dr. Young used prescribing data from the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey, which covers more than 5.7 billion adult (aged 18 and older) and 1.3 billion child visits to outpatient practices between 2009 and 2016 across all 50 U.S. states and Washington, D.C.

He gathered patient data on ICD-9-CM and ICD-10 diagnostic codes for infections and for diagnoses that “appeared like infections.” All of the patients who were included had received at least one oral antibiotic. Antibiotic prescribing was defined as visits that included an antibiotic per 1,000 total patient visits.

On the basis of previous research, Dr. Young and his colleagues then determined whether each antibiotic prescription was appropriate, possibly appropriate, or inappropriate. Patient demographics included age (younger than 18 years, 18-64 years, and older than 64 years), sex (male or female), race, and ethnicity (White, Black, more than one race, Hispanic/Latinx, and other). These data were used to evaluate overall and inappropriate use.

“The health care community needs to be really careful with the judicious use of antibiotics,” Dr. Young said. “We have good guidelines on antimicrobial stewardship both in the inpatient and outpatient settings, but sometimes we overlook the disparities and cultural implications held by some patients.”

Typical examples of socioeconomic and cultural factors at play included patients not being able to afford the antibiotics, having limited access to care, or not returning for a follow-up visit for whatever reason.

“Patients of Black and Hispanic descent often don’t have the same degree of established care that many White patients have,” Dr. Young noted.

In the future, Dr. Young wants to conduct research into whether patients are actually taking their prescribed antibiotics, as well as their outcomes. For example, he would like to investigate whether rates of antibiotic resistance or Clostridioides difficile infection are higher among Black patients.

Dr. Young and Dr. Bhakta have disclosed no relevant financial relationships.

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

LISBON – Two-thirds of antibiotic prescriptions written for Black patients and more than half of antibiotic prescriptions for Hispanic/Latinx patients are inappropriate, according to data from a study of antibiotic prescribing habits in U.S. doctors’ offices, hospital clinics, and emergency departments.

Eric Young, PharmD, PhD, from the University of Texas at Austin, and UT Health, San Antonio, presented his work as a poster at the 32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022.

“We were really surprised mainly by the racial findings, because Black patients have the highest overall and the highest inappropriate prescribing of antibiotics,” he told this news organization. “There was also a difference seen for age [across all ethnicities].”

Pediatric patients were found to have high overall prescribing but, notably, the lowest inappropriate prescribing among all the patient groups, reported Dr. Young. “This is interesting because oftentimes we think the more antibiotics are prescribed, then surely the greater the inappropriate prescribing would be too, but pediatricians actually have one of the lowest rates of inappropriate antibiotic prescribing. They do a great job.”

The study included more than 7 billion patient visits, 11.3% of which involved an antibiotic prescription.

The rate of antibiotic prescribing was 122 per 1,000 visits in Black patients and 139 per 1,000 visits in Hispanic patients, while in White patients, the rate was 109 per 1,000 visits. The rate was 114 per 1,000 visits in patients younger than 18 years and 170 per 1,000 visits in females.

Dr. Young found that almost 64% of antibiotic prescriptions written for Black patients and 58% for Hispanic patients were inappropriate. For White patients, the rate of inappropriate antibiotic prescribing was 56%. Similarly, 74% of prescriptions dispensed to patients aged 65 years and older and 58% to males were deemed inappropriate.

Kajal Bhakta, PharmD, BCACP, ambulatory care clinical pharmacist, University Health System, UT Health Science Center San Antonio, who was not involved in the study, pointed out that antibiotics are frequently prescribed without confirmation of an infection, owing to the fact that the verification process may delay care, especially in the outpatient setting.

Dr. Bhakta said that overprescribing in the elderly population and in certain ethnic groups was “likely due to socioeconomic and cultural factors. These prescribing methods may lead to unnecessary drug side effects and/or antimicrobial resistance.”

Regarding the patient-doctor consultation process, she pointed out that “older patients may have trouble describing their symptoms, and when those symptoms remain unresolved, providers may be more inclined to prescribe antibiotics to help.”

Sometimes overprescribing can occur because of the logistics involved in getting to the doctor’s office in the outpatient setting. “Sometimes patients struggle with transportation, as two separate trips to the doctor and pharmacy may not be feasible. Additionally, these same patients may have limited access to health care and therefore may use an urgent care facility for their acute infection–like symptoms,” Dr. Bhakta explained.

Dr. Young, who is of Asian descent, first became interested in disparities in health care when he noticed that ethnic minority groups showed greater hesitancy toward COVID-19 vaccination. “I noticed that there weren’t many Asians involved in previous trials and realized at this point that disparities were rampant.”

Dr. Young had been involved in investigating the overall use and the inappropriate use of antibiotics across the whole U.S. population when his interest in health disparities prompted him to study these patterns in specific demographic groups.

“Most previous data are derived from inpatient studies where the physician is giving the antibiotics,” said Dr. Young, who looked specifically at outpatient prescribing.

Dr. Young used prescribing data from the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey, which covers more than 5.7 billion adult (aged 18 and older) and 1.3 billion child visits to outpatient practices between 2009 and 2016 across all 50 U.S. states and Washington, D.C.

He gathered patient data on ICD-9-CM and ICD-10 diagnostic codes for infections and for diagnoses that “appeared like infections.” All of the patients who were included had received at least one oral antibiotic. Antibiotic prescribing was defined as visits that included an antibiotic per 1,000 total patient visits.

On the basis of previous research, Dr. Young and his colleagues then determined whether each antibiotic prescription was appropriate, possibly appropriate, or inappropriate. Patient demographics included age (younger than 18 years, 18-64 years, and older than 64 years), sex (male or female), race, and ethnicity (White, Black, more than one race, Hispanic/Latinx, and other). These data were used to evaluate overall and inappropriate use.

“The health care community needs to be really careful with the judicious use of antibiotics,” Dr. Young said. “We have good guidelines on antimicrobial stewardship both in the inpatient and outpatient settings, but sometimes we overlook the disparities and cultural implications held by some patients.”

Typical examples of socioeconomic and cultural factors at play included patients not being able to afford the antibiotics, having limited access to care, or not returning for a follow-up visit for whatever reason.

“Patients of Black and Hispanic descent often don’t have the same degree of established care that many White patients have,” Dr. Young noted.

In the future, Dr. Young wants to conduct research into whether patients are actually taking their prescribed antibiotics, as well as their outcomes. For example, he would like to investigate whether rates of antibiotic resistance or Clostridioides difficile infection are higher among Black patients.

Dr. Young and Dr. Bhakta have disclosed no relevant financial relationships.

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

LISBON – Two-thirds of antibiotic prescriptions written for Black patients and more than half of antibiotic prescriptions for Hispanic/Latinx patients are inappropriate, according to data from a study of antibiotic prescribing habits in U.S. doctors’ offices, hospital clinics, and emergency departments.

Eric Young, PharmD, PhD, from the University of Texas at Austin, and UT Health, San Antonio, presented his work as a poster at the 32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022.

“We were really surprised mainly by the racial findings, because Black patients have the highest overall and the highest inappropriate prescribing of antibiotics,” he told this news organization. “There was also a difference seen for age [across all ethnicities].”

Pediatric patients were found to have high overall prescribing but, notably, the lowest inappropriate prescribing among all the patient groups, reported Dr. Young. “This is interesting because oftentimes we think the more antibiotics are prescribed, then surely the greater the inappropriate prescribing would be too, but pediatricians actually have one of the lowest rates of inappropriate antibiotic prescribing. They do a great job.”

The study included more than 7 billion patient visits, 11.3% of which involved an antibiotic prescription.

The rate of antibiotic prescribing was 122 per 1,000 visits in Black patients and 139 per 1,000 visits in Hispanic patients, while in White patients, the rate was 109 per 1,000 visits. The rate was 114 per 1,000 visits in patients younger than 18 years and 170 per 1,000 visits in females.

Dr. Young found that almost 64% of antibiotic prescriptions written for Black patients and 58% for Hispanic patients were inappropriate. For White patients, the rate of inappropriate antibiotic prescribing was 56%. Similarly, 74% of prescriptions dispensed to patients aged 65 years and older and 58% to males were deemed inappropriate.

Kajal Bhakta, PharmD, BCACP, ambulatory care clinical pharmacist, University Health System, UT Health Science Center San Antonio, who was not involved in the study, pointed out that antibiotics are frequently prescribed without confirmation of an infection, owing to the fact that the verification process may delay care, especially in the outpatient setting.

Dr. Bhakta said that overprescribing in the elderly population and in certain ethnic groups was “likely due to socioeconomic and cultural factors. These prescribing methods may lead to unnecessary drug side effects and/or antimicrobial resistance.”

Regarding the patient-doctor consultation process, she pointed out that “older patients may have trouble describing their symptoms, and when those symptoms remain unresolved, providers may be more inclined to prescribe antibiotics to help.”

Sometimes overprescribing can occur because of the logistics involved in getting to the doctor’s office in the outpatient setting. “Sometimes patients struggle with transportation, as two separate trips to the doctor and pharmacy may not be feasible. Additionally, these same patients may have limited access to health care and therefore may use an urgent care facility for their acute infection–like symptoms,” Dr. Bhakta explained.

Dr. Young, who is of Asian descent, first became interested in disparities in health care when he noticed that ethnic minority groups showed greater hesitancy toward COVID-19 vaccination. “I noticed that there weren’t many Asians involved in previous trials and realized at this point that disparities were rampant.”

Dr. Young had been involved in investigating the overall use and the inappropriate use of antibiotics across the whole U.S. population when his interest in health disparities prompted him to study these patterns in specific demographic groups.

“Most previous data are derived from inpatient studies where the physician is giving the antibiotics,” said Dr. Young, who looked specifically at outpatient prescribing.

Dr. Young used prescribing data from the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey, which covers more than 5.7 billion adult (aged 18 and older) and 1.3 billion child visits to outpatient practices between 2009 and 2016 across all 50 U.S. states and Washington, D.C.

He gathered patient data on ICD-9-CM and ICD-10 diagnostic codes for infections and for diagnoses that “appeared like infections.” All of the patients who were included had received at least one oral antibiotic. Antibiotic prescribing was defined as visits that included an antibiotic per 1,000 total patient visits.

On the basis of previous research, Dr. Young and his colleagues then determined whether each antibiotic prescription was appropriate, possibly appropriate, or inappropriate. Patient demographics included age (younger than 18 years, 18-64 years, and older than 64 years), sex (male or female), race, and ethnicity (White, Black, more than one race, Hispanic/Latinx, and other). These data were used to evaluate overall and inappropriate use.

“The health care community needs to be really careful with the judicious use of antibiotics,” Dr. Young said. “We have good guidelines on antimicrobial stewardship both in the inpatient and outpatient settings, but sometimes we overlook the disparities and cultural implications held by some patients.”

Typical examples of socioeconomic and cultural factors at play included patients not being able to afford the antibiotics, having limited access to care, or not returning for a follow-up visit for whatever reason.

“Patients of Black and Hispanic descent often don’t have the same degree of established care that many White patients have,” Dr. Young noted.

In the future, Dr. Young wants to conduct research into whether patients are actually taking their prescribed antibiotics, as well as their outcomes. For example, he would like to investigate whether rates of antibiotic resistance or Clostridioides difficile infection are higher among Black patients.

Dr. Young and Dr. Bhakta have disclosed no relevant financial relationships.

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

LISBON – During the pandemic, critical and acute care hospitals with medium and high rates of antimicrobial resistance (AMR) showed significant increases in antibiotic prescriptions and longer durations of antibiotic treatment among all hospital admissions, and also in those patients who were bacterial culture negative, according to a large U.S.-based study.

The analysis across 271 U.S. hospitals also showed that AMR rates were significantly higher for pathogens during the pandemic period, compared with the prepandemic period in patients who were tested for SARS-CoV-2, and highest in SARS-CoV-2–positive patients.

More than a third of SARS-CoV-2–positive patients who were prescribed antibiotics were bacterial culture negative.

Findings of the study were presented by Vikas Gupta, PharmD, director of medical affairs at medical technology firm Becton Dickinson, at this year’s European Congress of Clinical Microbiology & Infectious Diseases. He conducted the study jointly with Karri Bauer, PharmD, from Merck Sharp & Dohme, Kenilworth, N.J., and colleagues.

“There are differences in AMR that go beyond COVID-positive admissions,” Dr. Gupta told this news organization. “There is opportunity for improvement especially with those hospitalized patients who had a negative culture result, or no culture collected.”

“We found a higher percentage of COVID-positive admissions that were prescribed antibacterial therapy even in those having [tested negative for bacteria] or no culture result,” said Dr. Gupta. “Our data also shows that the percentage of admissions with duration of antibacterial therapy over 3 days was significantly higher in COVID-positive but culture-negative/no culture patients, compared to other groups evaluated.”

Of all admissions prescribed antibiotics during the pandemic, 57.8% of SARS-CoV-2–positive patients were prescribed antibiotics whereas 88.1% of SARS-CoV-2–positive admissions were bacterial culture negative/no culture. Overall, prepandemic, 35% of admissions were prescribed antibiotics.

Duration of antibiotic therapy in the prepandemic era was an average of 3.5 days, compared with an average of 3.8 days overall in the pandemic and 5.7 days in patients who tested positive for SARS-CoV-2. Similarly, the percentage of patients who were bacterial culture negative or had no culture and received antibiotic therapy for more than 72 hours was 17.6% in the prepandemic era, compared with 19.2% overall in the pandemic era, and 41.1% in patients who tested positive for COVID-19.  

Dr. Gupta and Dr. Bauer wanted to look at all patients admitted to hospitals segmented by SARS-CoV-2 positive, negative, and not tested, to get a sense of how much antibiotic use there was and how long patients were on antibiotics. “We ultimately want to optimize and not overuse antibiotics and prescribe them for right period of time,” said Dr. Gupta.

“To date, there has been no conclusive evidence about the suggestion that the pandemic has led to increased AMR rates, so we aimed to evaluate the pandemic’s impact on AMR and antibiotic use across U.S. hospitals,” he explained.

The multicenter, retrospective cohort analysis made use of BD’s infection surveillance platform (BD HealthSight Infection Advisor with MedMined Insights) and was conducted across 271 U.S. critical access/acute care facilities, representing approximately 10%-13% of U.S. hospital admissions. It included all hospitalized patients with more than 1 day of in-patient admission. Patients were considered SARS-CoV-2 positive by polymerase chain reaction test or antigen test either 7 days or less prior to or within 14 days of admission.

Patients were categorized as hospitalized during the “prepandemic” period (July 1, 2019 through February 29, 2020) and the “pandemic” period (March 1, 2020 through Oct. 30, 2021) and were stratified based on their SARS-CoV-2 result. 

Investigators included all hospital admissions with an AMR event (first positive culture for select gram-negative or gram-positive pathogens that were reported as nonsusceptible across blood, urine, respiratory, intra-abdominal, skin/wound, and other sources).

The investigators calculated AMR rates at the patient-admission level and defined per 100 admissions. Also, they further evaluated AMR rates based on community onset (defined as culture collected ≤2 days from admission) or hospital onset (>2 days from admission). Finally, AMR rates were determined according to whether they related to prepandemic or pandemic periods. 

Hospitals were also categorized according to their AMR rates as low (<25%), medium (25%-75%), and high (>75%). 

Overall AMR rates were lower in the pandemic period, compared with the prepandemic period. However, reported Dr.Gupta, for hospital-onset pathogens specifically, AMR rates were significantly higher overall in the pandemic period and mostly driven by admissions tested for SARS-CoV-2 (whether positive or negative).

Hospitals with high AMR rates also tended to have more SARS-CoV-2 positive admissions (6.1% in high-AMR hospitals vs. 3% in low-AMR hospitals). The highest antibiotic-prescribing rates and highest duration of antibiotic use was also seen in those hospitals with highest AMR rates. 

Of the SARS-CoV-2 patients who were bacterial culture negative/no culture and were prescribed antibiotics, 36.5% were in hospitals with a high AMR rate. “Roughly one-third of patients without culture evidence of a bacterial infection were prescribed antibiotics in hospitals with a high AMR rate,” said Dr. Gupta.

The researchers wanted to tease out whether hospitals with high, moderate, or low AMR rates look different with respect to antibiotic-prescribing patterns. During the pandemic period, they found that hospitals with high and medium AMR rates experienced significant increases in antibiotic prescriptions and longer durations. Prepandemic, the overall hospital-onset AMR rate was 0.8 per 100 admissions, whereas during the pandemic this rose to 1.4 per 100 admissions in high-AMR hospitals and dropped to 0.4 in low-AMR hospitals.

SARS-CoV-2–positive admission rates were higher in facilities with medium (5.6%) and high AMR (6.1%) rates than those with low (3%) AMR rates. “We found that those with medium and high AMR rates were more likely to have COVID-positive admissions than facilities with low AMR rates,” Dr. Gupta said. “It appears as if COVID is contributing to AMR in the facilities.”

Asked for independent comment, Jason C. Gallagher, PharmD, BCPS, clinical professor at Temple University School of Pharmacy in Philadelphia, said in an interview, “It is not surprising that there was more antimicrobial resistance in patients with COVID than those without. Even though antibiotics do not work for COVID, they are often prescribed, and antibiotic use is a major risk factor for antimicrobial resistance. This is likely because clinicians are sometimes concerned about coinfections with bacteria (which are rare) and because hospitalized patients with severe COVID can acquire other infections as they are treated.”
 

Antibiotic stewardship programs

Antibiotic stewardship programs have been highly stressed during the pandemic, so the researchers hope their data support the need for better antibiotic stewardship practices during pandemic surges when control is more challenging.

Dr. Gupta explained that they were seeing interesting associations that can inform antimicrobial stewardship programs and teams. “We are not trying to imply causality,” he stressed.

It is a common practice for stewardship teams to evaluate the need for continuation of antibiotic therapy at 3 days, especially in patients who are culture negative or did not have a culture collected.

“Antibiotic time-out at 3 days is a recommended practice to evaluate for continuing antibiotic therapy based on the patient’s condition and culture results,” he said. “This is what made our study unique because we wanted to look at what percentage of admissions were prescribed antibiotics beyond 3 days and compare to the prepandemic period.”

Session moderator Evangelos J. Giamarellos-Bourboulis, MD, PhD, an assistant professor of internal medicine and infectious diseases, University of Athens, Greece, thanked Dr. Gupta for his “eloquent presentation” and sought to clarify whether the data “refer to antimicrobial use that was empirical or whether use was in hospitals with high AMR rates, or whether the approach was driven through microbiology?”

Dr. Gupta replied that this was why they evaluated the negative-culture and no-culture patients. “We wanted to get a measure of antibacterial use in this population too,” he said. “Definitely, there is empirical therapy as well as definitive therapy, but I think the negative and no-culture group provide a reference point where we see similar signals and trends to that of the overall population.”

An audience member also addressed a question to Dr. Gupta: “Did you look at the patient population, because in many cases, during COVID, these patients may have been more severe than in the prepandemic period?”

Dr. Gupta replied: “In our manuscript we’ve done an analysis where we adjusted for patient-level facility and regional-level factors. There are definitely differences in the patient populations but overall, these are pretty sick patients when we look at the level of severity overall.”

Dr. Gupta is an employee of and a shareholder in Becton Dickinson. Dr. Bauer is an employee of and a shareholder in Merck. Dr. Gallagher consults for many pharmaceutical companies including Merck.

Dr. Giamarellos-Bourboulis disclosed honoraria (paid to the University of Athens) from Abbott CH, Brahms Thermo Fisher GMBH Germany, GlaxoSmithKline, and Sobi; serving as a consultant for Abbott CH, Fab’nTech, InflaRx GmbH, UCB, Sobi, and Xbiotech; research grants (paid to the Hellenic Institute for the Study of Sepsis) from Abbott CH, BioMerieux France, Johnson & Johnson, MSD, Sobi, Thermo Fisher Brahms GmbH; and EU research funding: Horizon 2020 ITN European Sepsis Academy (granted to the University of Athens); Horizon 2020 ImmunoSep and RISinCOVID (granted to the Hellenic Institute for the Study of Sepsis); Horizon Health EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis).

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

LISBON – During the pandemic, critical and acute care hospitals with medium and high rates of antimicrobial resistance (AMR) showed significant increases in antibiotic prescriptions and longer durations of antibiotic treatment among all hospital admissions, and also in those patients who were bacterial culture negative, according to a large U.S.-based study.

The analysis across 271 U.S. hospitals also showed that AMR rates were significantly higher for pathogens during the pandemic period, compared with the prepandemic period in patients who were tested for SARS-CoV-2, and highest in SARS-CoV-2–positive patients.

More than a third of SARS-CoV-2–positive patients who were prescribed antibiotics were bacterial culture negative.

Findings of the study were presented by Vikas Gupta, PharmD, director of medical affairs at medical technology firm Becton Dickinson, at this year’s European Congress of Clinical Microbiology & Infectious Diseases. He conducted the study jointly with Karri Bauer, PharmD, from Merck Sharp & Dohme, Kenilworth, N.J., and colleagues.

“There are differences in AMR that go beyond COVID-positive admissions,” Dr. Gupta told this news organization. “There is opportunity for improvement especially with those hospitalized patients who had a negative culture result, or no culture collected.”

“We found a higher percentage of COVID-positive admissions that were prescribed antibacterial therapy even in those having [tested negative for bacteria] or no culture result,” said Dr. Gupta. “Our data also shows that the percentage of admissions with duration of antibacterial therapy over 3 days was significantly higher in COVID-positive but culture-negative/no culture patients, compared to other groups evaluated.”

Of all admissions prescribed antibiotics during the pandemic, 57.8% of SARS-CoV-2–positive patients were prescribed antibiotics whereas 88.1% of SARS-CoV-2–positive admissions were bacterial culture negative/no culture. Overall, prepandemic, 35% of admissions were prescribed antibiotics.

Duration of antibiotic therapy in the prepandemic era was an average of 3.5 days, compared with an average of 3.8 days overall in the pandemic and 5.7 days in patients who tested positive for SARS-CoV-2. Similarly, the percentage of patients who were bacterial culture negative or had no culture and received antibiotic therapy for more than 72 hours was 17.6% in the prepandemic era, compared with 19.2% overall in the pandemic era, and 41.1% in patients who tested positive for COVID-19.  

Dr. Gupta and Dr. Bauer wanted to look at all patients admitted to hospitals segmented by SARS-CoV-2 positive, negative, and not tested, to get a sense of how much antibiotic use there was and how long patients were on antibiotics. “We ultimately want to optimize and not overuse antibiotics and prescribe them for right period of time,” said Dr. Gupta.

“To date, there has been no conclusive evidence about the suggestion that the pandemic has led to increased AMR rates, so we aimed to evaluate the pandemic’s impact on AMR and antibiotic use across U.S. hospitals,” he explained.

The multicenter, retrospective cohort analysis made use of BD’s infection surveillance platform (BD HealthSight Infection Advisor with MedMined Insights) and was conducted across 271 U.S. critical access/acute care facilities, representing approximately 10%-13% of U.S. hospital admissions. It included all hospitalized patients with more than 1 day of in-patient admission. Patients were considered SARS-CoV-2 positive by polymerase chain reaction test or antigen test either 7 days or less prior to or within 14 days of admission.

Patients were categorized as hospitalized during the “prepandemic” period (July 1, 2019 through February 29, 2020) and the “pandemic” period (March 1, 2020 through Oct. 30, 2021) and were stratified based on their SARS-CoV-2 result. 

Investigators included all hospital admissions with an AMR event (first positive culture for select gram-negative or gram-positive pathogens that were reported as nonsusceptible across blood, urine, respiratory, intra-abdominal, skin/wound, and other sources).

The investigators calculated AMR rates at the patient-admission level and defined per 100 admissions. Also, they further evaluated AMR rates based on community onset (defined as culture collected ≤2 days from admission) or hospital onset (>2 days from admission). Finally, AMR rates were determined according to whether they related to prepandemic or pandemic periods. 

Hospitals were also categorized according to their AMR rates as low (<25%), medium (25%-75%), and high (>75%). 

Overall AMR rates were lower in the pandemic period, compared with the prepandemic period. However, reported Dr.Gupta, for hospital-onset pathogens specifically, AMR rates were significantly higher overall in the pandemic period and mostly driven by admissions tested for SARS-CoV-2 (whether positive or negative).

Hospitals with high AMR rates also tended to have more SARS-CoV-2 positive admissions (6.1% in high-AMR hospitals vs. 3% in low-AMR hospitals). The highest antibiotic-prescribing rates and highest duration of antibiotic use was also seen in those hospitals with highest AMR rates. 

Of the SARS-CoV-2 patients who were bacterial culture negative/no culture and were prescribed antibiotics, 36.5% were in hospitals with a high AMR rate. “Roughly one-third of patients without culture evidence of a bacterial infection were prescribed antibiotics in hospitals with a high AMR rate,” said Dr. Gupta.

The researchers wanted to tease out whether hospitals with high, moderate, or low AMR rates look different with respect to antibiotic-prescribing patterns. During the pandemic period, they found that hospitals with high and medium AMR rates experienced significant increases in antibiotic prescriptions and longer durations. Prepandemic, the overall hospital-onset AMR rate was 0.8 per 100 admissions, whereas during the pandemic this rose to 1.4 per 100 admissions in high-AMR hospitals and dropped to 0.4 in low-AMR hospitals.

SARS-CoV-2–positive admission rates were higher in facilities with medium (5.6%) and high AMR (6.1%) rates than those with low (3%) AMR rates. “We found that those with medium and high AMR rates were more likely to have COVID-positive admissions than facilities with low AMR rates,” Dr. Gupta said. “It appears as if COVID is contributing to AMR in the facilities.”

Asked for independent comment, Jason C. Gallagher, PharmD, BCPS, clinical professor at Temple University School of Pharmacy in Philadelphia, said in an interview, “It is not surprising that there was more antimicrobial resistance in patients with COVID than those without. Even though antibiotics do not work for COVID, they are often prescribed, and antibiotic use is a major risk factor for antimicrobial resistance. This is likely because clinicians are sometimes concerned about coinfections with bacteria (which are rare) and because hospitalized patients with severe COVID can acquire other infections as they are treated.”
 

Antibiotic stewardship programs

Antibiotic stewardship programs have been highly stressed during the pandemic, so the researchers hope their data support the need for better antibiotic stewardship practices during pandemic surges when control is more challenging.

Dr. Gupta explained that they were seeing interesting associations that can inform antimicrobial stewardship programs and teams. “We are not trying to imply causality,” he stressed.

It is a common practice for stewardship teams to evaluate the need for continuation of antibiotic therapy at 3 days, especially in patients who are culture negative or did not have a culture collected.

“Antibiotic time-out at 3 days is a recommended practice to evaluate for continuing antibiotic therapy based on the patient’s condition and culture results,” he said. “This is what made our study unique because we wanted to look at what percentage of admissions were prescribed antibiotics beyond 3 days and compare to the prepandemic period.”

Session moderator Evangelos J. Giamarellos-Bourboulis, MD, PhD, an assistant professor of internal medicine and infectious diseases, University of Athens, Greece, thanked Dr. Gupta for his “eloquent presentation” and sought to clarify whether the data “refer to antimicrobial use that was empirical or whether use was in hospitals with high AMR rates, or whether the approach was driven through microbiology?”

Dr. Gupta replied that this was why they evaluated the negative-culture and no-culture patients. “We wanted to get a measure of antibacterial use in this population too,” he said. “Definitely, there is empirical therapy as well as definitive therapy, but I think the negative and no-culture group provide a reference point where we see similar signals and trends to that of the overall population.”

An audience member also addressed a question to Dr. Gupta: “Did you look at the patient population, because in many cases, during COVID, these patients may have been more severe than in the prepandemic period?”

Dr. Gupta replied: “In our manuscript we’ve done an analysis where we adjusted for patient-level facility and regional-level factors. There are definitely differences in the patient populations but overall, these are pretty sick patients when we look at the level of severity overall.”

Dr. Gupta is an employee of and a shareholder in Becton Dickinson. Dr. Bauer is an employee of and a shareholder in Merck. Dr. Gallagher consults for many pharmaceutical companies including Merck.

Dr. Giamarellos-Bourboulis disclosed honoraria (paid to the University of Athens) from Abbott CH, Brahms Thermo Fisher GMBH Germany, GlaxoSmithKline, and Sobi; serving as a consultant for Abbott CH, Fab’nTech, InflaRx GmbH, UCB, Sobi, and Xbiotech; research grants (paid to the Hellenic Institute for the Study of Sepsis) from Abbott CH, BioMerieux France, Johnson & Johnson, MSD, Sobi, Thermo Fisher Brahms GmbH; and EU research funding: Horizon 2020 ITN European Sepsis Academy (granted to the University of Athens); Horizon 2020 ImmunoSep and RISinCOVID (granted to the Hellenic Institute for the Study of Sepsis); Horizon Health EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis).

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

LISBON – During the pandemic, critical and acute care hospitals with medium and high rates of antimicrobial resistance (AMR) showed significant increases in antibiotic prescriptions and longer durations of antibiotic treatment among all hospital admissions, and also in those patients who were bacterial culture negative, according to a large U.S.-based study.

The analysis across 271 U.S. hospitals also showed that AMR rates were significantly higher for pathogens during the pandemic period, compared with the prepandemic period in patients who were tested for SARS-CoV-2, and highest in SARS-CoV-2–positive patients.

More than a third of SARS-CoV-2–positive patients who were prescribed antibiotics were bacterial culture negative.

Findings of the study were presented by Vikas Gupta, PharmD, director of medical affairs at medical technology firm Becton Dickinson, at this year’s European Congress of Clinical Microbiology & Infectious Diseases. He conducted the study jointly with Karri Bauer, PharmD, from Merck Sharp & Dohme, Kenilworth, N.J., and colleagues.

“There are differences in AMR that go beyond COVID-positive admissions,” Dr. Gupta told this news organization. “There is opportunity for improvement especially with those hospitalized patients who had a negative culture result, or no culture collected.”

“We found a higher percentage of COVID-positive admissions that were prescribed antibacterial therapy even in those having [tested negative for bacteria] or no culture result,” said Dr. Gupta. “Our data also shows that the percentage of admissions with duration of antibacterial therapy over 3 days was significantly higher in COVID-positive but culture-negative/no culture patients, compared to other groups evaluated.”

Of all admissions prescribed antibiotics during the pandemic, 57.8% of SARS-CoV-2–positive patients were prescribed antibiotics whereas 88.1% of SARS-CoV-2–positive admissions were bacterial culture negative/no culture. Overall, prepandemic, 35% of admissions were prescribed antibiotics.

Duration of antibiotic therapy in the prepandemic era was an average of 3.5 days, compared with an average of 3.8 days overall in the pandemic and 5.7 days in patients who tested positive for SARS-CoV-2. Similarly, the percentage of patients who were bacterial culture negative or had no culture and received antibiotic therapy for more than 72 hours was 17.6% in the prepandemic era, compared with 19.2% overall in the pandemic era, and 41.1% in patients who tested positive for COVID-19.  

Dr. Gupta and Dr. Bauer wanted to look at all patients admitted to hospitals segmented by SARS-CoV-2 positive, negative, and not tested, to get a sense of how much antibiotic use there was and how long patients were on antibiotics. “We ultimately want to optimize and not overuse antibiotics and prescribe them for right period of time,” said Dr. Gupta.

“To date, there has been no conclusive evidence about the suggestion that the pandemic has led to increased AMR rates, so we aimed to evaluate the pandemic’s impact on AMR and antibiotic use across U.S. hospitals,” he explained.

The multicenter, retrospective cohort analysis made use of BD’s infection surveillance platform (BD HealthSight Infection Advisor with MedMined Insights) and was conducted across 271 U.S. critical access/acute care facilities, representing approximately 10%-13% of U.S. hospital admissions. It included all hospitalized patients with more than 1 day of in-patient admission. Patients were considered SARS-CoV-2 positive by polymerase chain reaction test or antigen test either 7 days or less prior to or within 14 days of admission.

Patients were categorized as hospitalized during the “prepandemic” period (July 1, 2019 through February 29, 2020) and the “pandemic” period (March 1, 2020 through Oct. 30, 2021) and were stratified based on their SARS-CoV-2 result. 

Investigators included all hospital admissions with an AMR event (first positive culture for select gram-negative or gram-positive pathogens that were reported as nonsusceptible across blood, urine, respiratory, intra-abdominal, skin/wound, and other sources).

The investigators calculated AMR rates at the patient-admission level and defined per 100 admissions. Also, they further evaluated AMR rates based on community onset (defined as culture collected ≤2 days from admission) or hospital onset (>2 days from admission). Finally, AMR rates were determined according to whether they related to prepandemic or pandemic periods. 

Hospitals were also categorized according to their AMR rates as low (<25%), medium (25%-75%), and high (>75%). 

Overall AMR rates were lower in the pandemic period, compared with the prepandemic period. However, reported Dr.Gupta, for hospital-onset pathogens specifically, AMR rates were significantly higher overall in the pandemic period and mostly driven by admissions tested for SARS-CoV-2 (whether positive or negative).

Hospitals with high AMR rates also tended to have more SARS-CoV-2 positive admissions (6.1% in high-AMR hospitals vs. 3% in low-AMR hospitals). The highest antibiotic-prescribing rates and highest duration of antibiotic use was also seen in those hospitals with highest AMR rates. 

Of the SARS-CoV-2 patients who were bacterial culture negative/no culture and were prescribed antibiotics, 36.5% were in hospitals with a high AMR rate. “Roughly one-third of patients without culture evidence of a bacterial infection were prescribed antibiotics in hospitals with a high AMR rate,” said Dr. Gupta.

The researchers wanted to tease out whether hospitals with high, moderate, or low AMR rates look different with respect to antibiotic-prescribing patterns. During the pandemic period, they found that hospitals with high and medium AMR rates experienced significant increases in antibiotic prescriptions and longer durations. Prepandemic, the overall hospital-onset AMR rate was 0.8 per 100 admissions, whereas during the pandemic this rose to 1.4 per 100 admissions in high-AMR hospitals and dropped to 0.4 in low-AMR hospitals.

SARS-CoV-2–positive admission rates were higher in facilities with medium (5.6%) and high AMR (6.1%) rates than those with low (3%) AMR rates. “We found that those with medium and high AMR rates were more likely to have COVID-positive admissions than facilities with low AMR rates,” Dr. Gupta said. “It appears as if COVID is contributing to AMR in the facilities.”

Asked for independent comment, Jason C. Gallagher, PharmD, BCPS, clinical professor at Temple University School of Pharmacy in Philadelphia, said in an interview, “It is not surprising that there was more antimicrobial resistance in patients with COVID than those without. Even though antibiotics do not work for COVID, they are often prescribed, and antibiotic use is a major risk factor for antimicrobial resistance. This is likely because clinicians are sometimes concerned about coinfections with bacteria (which are rare) and because hospitalized patients with severe COVID can acquire other infections as they are treated.”
 

Antibiotic stewardship programs

Antibiotic stewardship programs have been highly stressed during the pandemic, so the researchers hope their data support the need for better antibiotic stewardship practices during pandemic surges when control is more challenging.

Dr. Gupta explained that they were seeing interesting associations that can inform antimicrobial stewardship programs and teams. “We are not trying to imply causality,” he stressed.

It is a common practice for stewardship teams to evaluate the need for continuation of antibiotic therapy at 3 days, especially in patients who are culture negative or did not have a culture collected.

“Antibiotic time-out at 3 days is a recommended practice to evaluate for continuing antibiotic therapy based on the patient’s condition and culture results,” he said. “This is what made our study unique because we wanted to look at what percentage of admissions were prescribed antibiotics beyond 3 days and compare to the prepandemic period.”

Session moderator Evangelos J. Giamarellos-Bourboulis, MD, PhD, an assistant professor of internal medicine and infectious diseases, University of Athens, Greece, thanked Dr. Gupta for his “eloquent presentation” and sought to clarify whether the data “refer to antimicrobial use that was empirical or whether use was in hospitals with high AMR rates, or whether the approach was driven through microbiology?”

Dr. Gupta replied that this was why they evaluated the negative-culture and no-culture patients. “We wanted to get a measure of antibacterial use in this population too,” he said. “Definitely, there is empirical therapy as well as definitive therapy, but I think the negative and no-culture group provide a reference point where we see similar signals and trends to that of the overall population.”

An audience member also addressed a question to Dr. Gupta: “Did you look at the patient population, because in many cases, during COVID, these patients may have been more severe than in the prepandemic period?”

Dr. Gupta replied: “In our manuscript we’ve done an analysis where we adjusted for patient-level facility and regional-level factors. There are definitely differences in the patient populations but overall, these are pretty sick patients when we look at the level of severity overall.”

Dr. Gupta is an employee of and a shareholder in Becton Dickinson. Dr. Bauer is an employee of and a shareholder in Merck. Dr. Gallagher consults for many pharmaceutical companies including Merck.

Dr. Giamarellos-Bourboulis disclosed honoraria (paid to the University of Athens) from Abbott CH, Brahms Thermo Fisher GMBH Germany, GlaxoSmithKline, and Sobi; serving as a consultant for Abbott CH, Fab’nTech, InflaRx GmbH, UCB, Sobi, and Xbiotech; research grants (paid to the Hellenic Institute for the Study of Sepsis) from Abbott CH, BioMerieux France, Johnson & Johnson, MSD, Sobi, Thermo Fisher Brahms GmbH; and EU research funding: Horizon 2020 ITN European Sepsis Academy (granted to the University of Athens); Horizon 2020 ImmunoSep and RISinCOVID (granted to the Hellenic Institute for the Study of Sepsis); Horizon Health EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis).

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

The U.S. Preventive Services Task Force has published a final recommendation statement on aspirin use to prevent cardiovascular disease.

The statement advises against starting aspirin for the primary prevention of cardiovascular disease in individuals aged 60 years or older.

For people aged 40-59 years, the USPSTF suggests that aspirin could be considered in those at increased risk of cardiovascular disease (10-year risk of 10% or greater) but that the decision should be individualized.

It notes that in the 40-59 age group, evidence indicates that the net benefit of aspirin use is small, and that persons who are not at increased risk for bleeding are more likely to benefit.

It adds that these recommendations apply only to people who do not have a history of cardiovascular disease and are not already taking daily aspirin.

The USPSTF statement was published online in the Journal of the American Medical Association. It is accompanied by an evidence review, a modeling study, a patient page, and an editorial.

A draft version of the recommendation statement, evidence review, and modeling report were previously available for public comment. The final recommendation statement is consistent with the draft version.

The task force concludes that there is adequate evidence that low-dose aspirin has a small benefit to reduce risk for cardiovascular events (nonfatal myocardial infarction and stroke) in adults 40 years or older who have no history of cardiovascular disease but are at increased cardiovascular risk.

Evidence shows that the absolute magnitude of benefit increases with increasing 10-year cardiovascular risk and that the magnitude of the lifetime benefits is greater when aspirin is initiated at a younger age.

But it adds that there is also adequate evidence that aspirin use in adults increases the risk for gastrointestinal bleeding, intracranial bleeding, and hemorrhagic stroke. The USPSTF determined that the magnitude of the harms is small overall but increases in older age groups, particularly in adults older than 60 years.

For patients who are eligible and choose to start taking aspirin, the benefits become smaller with advancing age, and data suggest that clinicians and patients should consider stopping aspirin use around age 75 years, the statement advises.

It also says that evidence is unclear whether aspirin use reduces the risk of colorectal cancer incidence or mortality.

USPSTF vice chair Michael Barry, MD, director of the Informed Medical Decisions Program in the Health Decision Sciences Center at Massachusetts General Hospital, Boston, told this news organization that these recommendations apply only to patients not taking aspirin already and who have no evidence of existing cardiovascular disease.

“In adults aged 60 or over we do not recommend starting aspirin for primary prevention. That is because in this age group the risk of bleeding outweighs the cardiovascular benefit,” he said.

“For adults aged 40-59 years with a greater than 10% predicted risk of cardiovascular disease, there appears to be a net benefit from taking aspirin, but this net benefit is relatively small and will vary with other factors such as magnitude of cardiovascular and bleeding risk. People should talk to their physician about these factors and whether to take aspirin or not,” he added.      

Dr. Barry noted that these recommendations do not apply to people who are already taking aspirin for primary prevention. “These people need to talk to their physicians about whether they should continue. They need to review the reasons why they started aspirin in the first place, and they need to have their bleeding risk evaluated. Someone who has taken aspirin long term without any bleeding complications has a lower risk of future bleeding complications,” he said.

The task force recommends an aspirin dose of 81 mg daily for those people deciding to take aspirin for primary prevention.    

“There is an abundance of evidence that less than 100 mg a day is enough. The lower the dose the lower the bleeding risk. So, the most convenient dose is the widely available 81-mg baby aspirin tablet,” Dr. Barry noted. “While enteric coated products are meant to reduce gastric irritation, the data do not show any difference in bleeding risk between various aspirin formulations,” he added.

Dr. Barry pointed out that aspirin is just one tool for reducing cardiovascular risk.

“People can reduce their risk significantly in many other ways including taking regular exercise, eating a healthy diet, controlling blood pressure and diabetes, and taking statins if they are at increased cardiovascular risk.”

He noted that recent trials have suggested that aspirin has only a marginal value over and above all these other factors. And the risk reduction with aspirin is smaller than with some other interventions.

“For example, aspirin is associated with a 12% reduction in MI whereas statins are associated with a 25%-30% reduction. Statins are a more powerful tool in reducing cardiovascular risk than aspirin, so perhaps people should consider taking statins first. The benefit of aspirin may be smaller in individuals already taking a statin, and clinicians need to think about the big picture,” Dr. Barry said.

He explained that physicians need to evaluate the cardiovascular and bleeding risk in each individual patient. “While there are widely available tools to estimate cardiovascular risk, there are no easy tools yet available to evaluate bleeding risk, so physicians need to consider clinical factors such as history of peptic ulcers.”

He suggests for the many people who have an average bleeding risk, then personal preference may come into play. “In the 40-59 age group, the benefits and harms of aspirin are pretty well-balanced. For the average person we think there may be a small net benefit, but this is small enough for personal preference to be considered as well.”
 

Pendulum swinging away from aspirin use

In an editorial accompanying publication of the task force statement in JAMA, Allan S. Brett, MD, clinical professor of internal medicine at the University of Colorado at Denver, Aurora, explains that the USPSTF recommendations on aspirin use for primary prevention of cardiovascular disease have changed numerous times over the past 30 years, with the last update in 2016 narrowing the eligible population.

In the new recommendation statement, “the pendulum has swung further away from aspirin prophylaxis for primary prevention: The guideline does not recommend routine preventive aspirin for anyone,” Dr. Brett notes.

He points out that an important development between the 2016 and current version was the publication in 2018 of three large placebo-controlled randomized clinical trials of primary prevention with aspirin – ARRIVE, ASPREE and ASCEND – which taken together “cast doubt about net benefit for aspirin prophylaxis in current practice.”

Asked how physicians should go about “individualizing” the decision on the use of aspirin in the 40-59 age group at increased cardiovascular risk, Dr. Brett suggests that some patents will have a general philosophy of medical care of “don’t prescribe medication for me unless there is strong evidence to support it,” while others may favor preventive interventions even in borderline cases.

But he notes that many patients have no strong general preferences and often ask a trusted clinician to decide for them. “For such patients, the best approach is for clinicians to be knowledgeable about the data on primary prevention with aspirin. Close reading of the new USPSTF guideline and its companion evidence review, and becoming familiar with the three more recent aspirin trials, is a good way to prepare for these clinical encounters,” he concludes.
 

A cardiologist’s view

Commenting on the task force statement for this news organization, Andrew Freeman, MD, a cardiologist at National Jewish Health, Denver, noted that cardiology societies are already making similar recommendations on aspirin use in primary prevention. “The American College of Cardiology prevention guidelines have been giving similar advice for a couple of years now. It takes a few years for professional societies to catch up with each other,” he said.

“Over the last few years, it has become obvious that the benefit of aspirin is not really very positive until a patient has had a cardiovascular event. In primary prevention, it doesn’t become beneficial unless they are at quite a high risk of having an event,” Dr. Freeman noted.

“In general, most cardiologists are now telling people that, despite what they may have been told in the past, they don’t need to be on aspirin unless they have had a cardiovascular event,” he added. “Our understanding has changed over the years and the weight of evidence has now become clear that the risk of bleeding is not insignificant.”

Dr. Freeman agreed with the shared decision-making advocated for patients in the 40-59 age group. “If a patient is particularly worried about a family history of heart disease, taking aspirin may make some sense, but for most people who have not had a cardiovascular event, the net benefit is very low and gets lower with age as the bleeding risk increases,” he said.  

The USPSTF is an independent, voluntary body. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

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

The U.S. Preventive Services Task Force has published a final recommendation statement on aspirin use to prevent cardiovascular disease.

The statement advises against starting aspirin for the primary prevention of cardiovascular disease in individuals aged 60 years or older.

For people aged 40-59 years, the USPSTF suggests that aspirin could be considered in those at increased risk of cardiovascular disease (10-year risk of 10% or greater) but that the decision should be individualized.

It notes that in the 40-59 age group, evidence indicates that the net benefit of aspirin use is small, and that persons who are not at increased risk for bleeding are more likely to benefit.

It adds that these recommendations apply only to people who do not have a history of cardiovascular disease and are not already taking daily aspirin.

The USPSTF statement was published online in the Journal of the American Medical Association. It is accompanied by an evidence review, a modeling study, a patient page, and an editorial.

A draft version of the recommendation statement, evidence review, and modeling report were previously available for public comment. The final recommendation statement is consistent with the draft version.

The task force concludes that there is adequate evidence that low-dose aspirin has a small benefit to reduce risk for cardiovascular events (nonfatal myocardial infarction and stroke) in adults 40 years or older who have no history of cardiovascular disease but are at increased cardiovascular risk.

Evidence shows that the absolute magnitude of benefit increases with increasing 10-year cardiovascular risk and that the magnitude of the lifetime benefits is greater when aspirin is initiated at a younger age.

But it adds that there is also adequate evidence that aspirin use in adults increases the risk for gastrointestinal bleeding, intracranial bleeding, and hemorrhagic stroke. The USPSTF determined that the magnitude of the harms is small overall but increases in older age groups, particularly in adults older than 60 years.

For patients who are eligible and choose to start taking aspirin, the benefits become smaller with advancing age, and data suggest that clinicians and patients should consider stopping aspirin use around age 75 years, the statement advises.

It also says that evidence is unclear whether aspirin use reduces the risk of colorectal cancer incidence or mortality.

USPSTF vice chair Michael Barry, MD, director of the Informed Medical Decisions Program in the Health Decision Sciences Center at Massachusetts General Hospital, Boston, told this news organization that these recommendations apply only to patients not taking aspirin already and who have no evidence of existing cardiovascular disease.

“In adults aged 60 or over we do not recommend starting aspirin for primary prevention. That is because in this age group the risk of bleeding outweighs the cardiovascular benefit,” he said.

“For adults aged 40-59 years with a greater than 10% predicted risk of cardiovascular disease, there appears to be a net benefit from taking aspirin, but this net benefit is relatively small and will vary with other factors such as magnitude of cardiovascular and bleeding risk. People should talk to their physician about these factors and whether to take aspirin or not,” he added.      

Dr. Barry noted that these recommendations do not apply to people who are already taking aspirin for primary prevention. “These people need to talk to their physicians about whether they should continue. They need to review the reasons why they started aspirin in the first place, and they need to have their bleeding risk evaluated. Someone who has taken aspirin long term without any bleeding complications has a lower risk of future bleeding complications,” he said.

The task force recommends an aspirin dose of 81 mg daily for those people deciding to take aspirin for primary prevention.    

“There is an abundance of evidence that less than 100 mg a day is enough. The lower the dose the lower the bleeding risk. So, the most convenient dose is the widely available 81-mg baby aspirin tablet,” Dr. Barry noted. “While enteric coated products are meant to reduce gastric irritation, the data do not show any difference in bleeding risk between various aspirin formulations,” he added.

Dr. Barry pointed out that aspirin is just one tool for reducing cardiovascular risk.

“People can reduce their risk significantly in many other ways including taking regular exercise, eating a healthy diet, controlling blood pressure and diabetes, and taking statins if they are at increased cardiovascular risk.”

He noted that recent trials have suggested that aspirin has only a marginal value over and above all these other factors. And the risk reduction with aspirin is smaller than with some other interventions.

“For example, aspirin is associated with a 12% reduction in MI whereas statins are associated with a 25%-30% reduction. Statins are a more powerful tool in reducing cardiovascular risk than aspirin, so perhaps people should consider taking statins first. The benefit of aspirin may be smaller in individuals already taking a statin, and clinicians need to think about the big picture,” Dr. Barry said.

He explained that physicians need to evaluate the cardiovascular and bleeding risk in each individual patient. “While there are widely available tools to estimate cardiovascular risk, there are no easy tools yet available to evaluate bleeding risk, so physicians need to consider clinical factors such as history of peptic ulcers.”

He suggests for the many people who have an average bleeding risk, then personal preference may come into play. “In the 40-59 age group, the benefits and harms of aspirin are pretty well-balanced. For the average person we think there may be a small net benefit, but this is small enough for personal preference to be considered as well.”
 

Pendulum swinging away from aspirin use

In an editorial accompanying publication of the task force statement in JAMA, Allan S. Brett, MD, clinical professor of internal medicine at the University of Colorado at Denver, Aurora, explains that the USPSTF recommendations on aspirin use for primary prevention of cardiovascular disease have changed numerous times over the past 30 years, with the last update in 2016 narrowing the eligible population.

In the new recommendation statement, “the pendulum has swung further away from aspirin prophylaxis for primary prevention: The guideline does not recommend routine preventive aspirin for anyone,” Dr. Brett notes.

He points out that an important development between the 2016 and current version was the publication in 2018 of three large placebo-controlled randomized clinical trials of primary prevention with aspirin – ARRIVE, ASPREE and ASCEND – which taken together “cast doubt about net benefit for aspirin prophylaxis in current practice.”

Asked how physicians should go about “individualizing” the decision on the use of aspirin in the 40-59 age group at increased cardiovascular risk, Dr. Brett suggests that some patents will have a general philosophy of medical care of “don’t prescribe medication for me unless there is strong evidence to support it,” while others may favor preventive interventions even in borderline cases.

But he notes that many patients have no strong general preferences and often ask a trusted clinician to decide for them. “For such patients, the best approach is for clinicians to be knowledgeable about the data on primary prevention with aspirin. Close reading of the new USPSTF guideline and its companion evidence review, and becoming familiar with the three more recent aspirin trials, is a good way to prepare for these clinical encounters,” he concludes.
 

A cardiologist’s view

Commenting on the task force statement for this news organization, Andrew Freeman, MD, a cardiologist at National Jewish Health, Denver, noted that cardiology societies are already making similar recommendations on aspirin use in primary prevention. “The American College of Cardiology prevention guidelines have been giving similar advice for a couple of years now. It takes a few years for professional societies to catch up with each other,” he said.

“Over the last few years, it has become obvious that the benefit of aspirin is not really very positive until a patient has had a cardiovascular event. In primary prevention, it doesn’t become beneficial unless they are at quite a high risk of having an event,” Dr. Freeman noted.

“In general, most cardiologists are now telling people that, despite what they may have been told in the past, they don’t need to be on aspirin unless they have had a cardiovascular event,” he added. “Our understanding has changed over the years and the weight of evidence has now become clear that the risk of bleeding is not insignificant.”

Dr. Freeman agreed with the shared decision-making advocated for patients in the 40-59 age group. “If a patient is particularly worried about a family history of heart disease, taking aspirin may make some sense, but for most people who have not had a cardiovascular event, the net benefit is very low and gets lower with age as the bleeding risk increases,” he said.  

The USPSTF is an independent, voluntary body. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

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

The U.S. Preventive Services Task Force has published a final recommendation statement on aspirin use to prevent cardiovascular disease.

The statement advises against starting aspirin for the primary prevention of cardiovascular disease in individuals aged 60 years or older.

For people aged 40-59 years, the USPSTF suggests that aspirin could be considered in those at increased risk of cardiovascular disease (10-year risk of 10% or greater) but that the decision should be individualized.

It notes that in the 40-59 age group, evidence indicates that the net benefit of aspirin use is small, and that persons who are not at increased risk for bleeding are more likely to benefit.

It adds that these recommendations apply only to people who do not have a history of cardiovascular disease and are not already taking daily aspirin.

The USPSTF statement was published online in the Journal of the American Medical Association. It is accompanied by an evidence review, a modeling study, a patient page, and an editorial.

A draft version of the recommendation statement, evidence review, and modeling report were previously available for public comment. The final recommendation statement is consistent with the draft version.

The task force concludes that there is adequate evidence that low-dose aspirin has a small benefit to reduce risk for cardiovascular events (nonfatal myocardial infarction and stroke) in adults 40 years or older who have no history of cardiovascular disease but are at increased cardiovascular risk.

Evidence shows that the absolute magnitude of benefit increases with increasing 10-year cardiovascular risk and that the magnitude of the lifetime benefits is greater when aspirin is initiated at a younger age.

But it adds that there is also adequate evidence that aspirin use in adults increases the risk for gastrointestinal bleeding, intracranial bleeding, and hemorrhagic stroke. The USPSTF determined that the magnitude of the harms is small overall but increases in older age groups, particularly in adults older than 60 years.

For patients who are eligible and choose to start taking aspirin, the benefits become smaller with advancing age, and data suggest that clinicians and patients should consider stopping aspirin use around age 75 years, the statement advises.

It also says that evidence is unclear whether aspirin use reduces the risk of colorectal cancer incidence or mortality.

USPSTF vice chair Michael Barry, MD, director of the Informed Medical Decisions Program in the Health Decision Sciences Center at Massachusetts General Hospital, Boston, told this news organization that these recommendations apply only to patients not taking aspirin already and who have no evidence of existing cardiovascular disease.

“In adults aged 60 or over we do not recommend starting aspirin for primary prevention. That is because in this age group the risk of bleeding outweighs the cardiovascular benefit,” he said.

“For adults aged 40-59 years with a greater than 10% predicted risk of cardiovascular disease, there appears to be a net benefit from taking aspirin, but this net benefit is relatively small and will vary with other factors such as magnitude of cardiovascular and bleeding risk. People should talk to their physician about these factors and whether to take aspirin or not,” he added.      

Dr. Barry noted that these recommendations do not apply to people who are already taking aspirin for primary prevention. “These people need to talk to their physicians about whether they should continue. They need to review the reasons why they started aspirin in the first place, and they need to have their bleeding risk evaluated. Someone who has taken aspirin long term without any bleeding complications has a lower risk of future bleeding complications,” he said.

The task force recommends an aspirin dose of 81 mg daily for those people deciding to take aspirin for primary prevention.    

“There is an abundance of evidence that less than 100 mg a day is enough. The lower the dose the lower the bleeding risk. So, the most convenient dose is the widely available 81-mg baby aspirin tablet,” Dr. Barry noted. “While enteric coated products are meant to reduce gastric irritation, the data do not show any difference in bleeding risk between various aspirin formulations,” he added.

Dr. Barry pointed out that aspirin is just one tool for reducing cardiovascular risk.

“People can reduce their risk significantly in many other ways including taking regular exercise, eating a healthy diet, controlling blood pressure and diabetes, and taking statins if they are at increased cardiovascular risk.”

He noted that recent trials have suggested that aspirin has only a marginal value over and above all these other factors. And the risk reduction with aspirin is smaller than with some other interventions.

“For example, aspirin is associated with a 12% reduction in MI whereas statins are associated with a 25%-30% reduction. Statins are a more powerful tool in reducing cardiovascular risk than aspirin, so perhaps people should consider taking statins first. The benefit of aspirin may be smaller in individuals already taking a statin, and clinicians need to think about the big picture,” Dr. Barry said.

He explained that physicians need to evaluate the cardiovascular and bleeding risk in each individual patient. “While there are widely available tools to estimate cardiovascular risk, there are no easy tools yet available to evaluate bleeding risk, so physicians need to consider clinical factors such as history of peptic ulcers.”

He suggests for the many people who have an average bleeding risk, then personal preference may come into play. “In the 40-59 age group, the benefits and harms of aspirin are pretty well-balanced. For the average person we think there may be a small net benefit, but this is small enough for personal preference to be considered as well.”
 

Pendulum swinging away from aspirin use

In an editorial accompanying publication of the task force statement in JAMA, Allan S. Brett, MD, clinical professor of internal medicine at the University of Colorado at Denver, Aurora, explains that the USPSTF recommendations on aspirin use for primary prevention of cardiovascular disease have changed numerous times over the past 30 years, with the last update in 2016 narrowing the eligible population.

In the new recommendation statement, “the pendulum has swung further away from aspirin prophylaxis for primary prevention: The guideline does not recommend routine preventive aspirin for anyone,” Dr. Brett notes.

He points out that an important development between the 2016 and current version was the publication in 2018 of three large placebo-controlled randomized clinical trials of primary prevention with aspirin – ARRIVE, ASPREE and ASCEND – which taken together “cast doubt about net benefit for aspirin prophylaxis in current practice.”

Asked how physicians should go about “individualizing” the decision on the use of aspirin in the 40-59 age group at increased cardiovascular risk, Dr. Brett suggests that some patents will have a general philosophy of medical care of “don’t prescribe medication for me unless there is strong evidence to support it,” while others may favor preventive interventions even in borderline cases.

But he notes that many patients have no strong general preferences and often ask a trusted clinician to decide for them. “For such patients, the best approach is for clinicians to be knowledgeable about the data on primary prevention with aspirin. Close reading of the new USPSTF guideline and its companion evidence review, and becoming familiar with the three more recent aspirin trials, is a good way to prepare for these clinical encounters,” he concludes.
 

A cardiologist’s view

Commenting on the task force statement for this news organization, Andrew Freeman, MD, a cardiologist at National Jewish Health, Denver, noted that cardiology societies are already making similar recommendations on aspirin use in primary prevention. “The American College of Cardiology prevention guidelines have been giving similar advice for a couple of years now. It takes a few years for professional societies to catch up with each other,” he said.

“Over the last few years, it has become obvious that the benefit of aspirin is not really very positive until a patient has had a cardiovascular event. In primary prevention, it doesn’t become beneficial unless they are at quite a high risk of having an event,” Dr. Freeman noted.

“In general, most cardiologists are now telling people that, despite what they may have been told in the past, they don’t need to be on aspirin unless they have had a cardiovascular event,” he added. “Our understanding has changed over the years and the weight of evidence has now become clear that the risk of bleeding is not insignificant.”

Dr. Freeman agreed with the shared decision-making advocated for patients in the 40-59 age group. “If a patient is particularly worried about a family history of heart disease, taking aspirin may make some sense, but for most people who have not had a cardiovascular event, the net benefit is very low and gets lower with age as the bleeding risk increases,” he said.  

The USPSTF is an independent, voluntary body. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

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

Antidepressant use is not associated with significant improvement in health-related quality of life (HRQoL) in patients with depression, new research suggests.

Researchers who conducted the study admit this finding was unexpected, and outside experts say no firm conclusions can be drawn from the research.

“Of course we were surprised by the results,” first author Omar Almohammed, PharmD, PhD, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, told this news organization.

“We were expecting to see some positive impact with the use of antidepressant medications on the HRQoL measures when we compared these patients to patients that did not use antidepressant medications,” Dr. Almohammed said.

The study was published online  in PLOS ONE.
 

Controversial impact on quality of life

Depression is known to harm HRQoL. Despite evidence that antidepressants improve depressed mood, their effect on patients’ overall well-being and HRQoL remains controversial.

The researchers examined the effect of antidepressants on HRQoL in adults with depression using 11 years of data from the U.S. Medical Expenditures Panel Survey (MEPS), a large longitudinal survey that tracks health service use in the United States. HRQoL was measured using the 12-item Short Form Health Survey (SF-12).

On average, about 17.5 million adults were diagnosed with depression each year during the study period (2005-2016). More than half (57.6%) of these patients were treated with antidepressants.

Patients with depression had an average age of 48.3 years. Women made up more than two-thirds of the total sample (68%), and more women than men received antidepressants (61% vs. 52%).

Compared with no antidepressant use, antidepressant use was associated with some improvement on the mental, but not physical, component of the SF-12, the researchers report.

However, difference-in-differences (D-I-D) univariate analysis showed no significant difference between adults using and not using antidepressants in the SF-12 physical (-0.35 vs. -0.34; P = .9,595) or mental component (1.28 vs. 1.13; P = .6,405).

“The multivariate D-I-D analyses ensured the robustness of these results,” the researchers note.

The change in HRQoL observed in patients using antidepressants was not significantly different from that seen among peers not using these drugs, the researchers report.

“We are not saying that antidepressant medications are not helpful at all; HRQoL is only one of many measures intended to assess health outcomes,” Dr. Almohammed told this news organization.

“Based on our research design and data, we can only say that patients who used antidepressant medications did not experience better change in terms of HRQoL compared to patients who did not use antidepressant medications,” he said.

“These patients may have had some improvement on other clinical outcome measures, but that clinical improvement did not have a significant positive impact on HRQoL,” he noted.

“We still recommend that patients continue using their antidepressant medications, but they may want to ask their doctors to provide them with other nonpharmacologic interventions as this may have additional impact on their HRQoL,” Dr. Almohammed said.

Further research is needed to address a “gap in knowledge” about the impact of nondrug interventions – alone or in combination with antidepressant medications – on patients’ HRQoL, Dr. Almohammed added.
 

Experts weigh in

Several experts weighed in on the study in a statement from the British nonprofit Science Media Center.

Gemma Lewis, PhD, with University College London (UCL), noted that “clinical trials with experimental designs have found that antidepressants improve mental health-related quality of life.”

University College London

Bruce Jancin/MDedge News

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

Antidepressant use is not associated with significant improvement in health-related quality of life (HRQoL) in patients with depression, new research suggests.

Researchers who conducted the study admit this finding was unexpected, and outside experts say no firm conclusions can be drawn from the research.

“Of course we were surprised by the results,” first author Omar Almohammed, PharmD, PhD, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, told this news organization.

“We were expecting to see some positive impact with the use of antidepressant medications on the HRQoL measures when we compared these patients to patients that did not use antidepressant medications,” Dr. Almohammed said.

The study was published online  in PLOS ONE.
 

Controversial impact on quality of life

Depression is known to harm HRQoL. Despite evidence that antidepressants improve depressed mood, their effect on patients’ overall well-being and HRQoL remains controversial.

The researchers examined the effect of antidepressants on HRQoL in adults with depression using 11 years of data from the U.S. Medical Expenditures Panel Survey (MEPS), a large longitudinal survey that tracks health service use in the United States. HRQoL was measured using the 12-item Short Form Health Survey (SF-12).

On average, about 17.5 million adults were diagnosed with depression each year during the study period (2005-2016). More than half (57.6%) of these patients were treated with antidepressants.

Patients with depression had an average age of 48.3 years. Women made up more than two-thirds of the total sample (68%), and more women than men received antidepressants (61% vs. 52%).

Compared with no antidepressant use, antidepressant use was associated with some improvement on the mental, but not physical, component of the SF-12, the researchers report.

However, difference-in-differences (D-I-D) univariate analysis showed no significant difference between adults using and not using antidepressants in the SF-12 physical (-0.35 vs. -0.34; P = .9,595) or mental component (1.28 vs. 1.13; P = .6,405).

“The multivariate D-I-D analyses ensured the robustness of these results,” the researchers note.

The change in HRQoL observed in patients using antidepressants was not significantly different from that seen among peers not using these drugs, the researchers report.

“We are not saying that antidepressant medications are not helpful at all; HRQoL is only one of many measures intended to assess health outcomes,” Dr. Almohammed told this news organization.

“Based on our research design and data, we can only say that patients who used antidepressant medications did not experience better change in terms of HRQoL compared to patients who did not use antidepressant medications,” he said.

“These patients may have had some improvement on other clinical outcome measures, but that clinical improvement did not have a significant positive impact on HRQoL,” he noted.

“We still recommend that patients continue using their antidepressant medications, but they may want to ask their doctors to provide them with other nonpharmacologic interventions as this may have additional impact on their HRQoL,” Dr. Almohammed said.

Further research is needed to address a “gap in knowledge” about the impact of nondrug interventions – alone or in combination with antidepressant medications – on patients’ HRQoL, Dr. Almohammed added.
 

Experts weigh in

Several experts weighed in on the study in a statement from the British nonprofit Science Media Center.

Gemma Lewis, PhD, with University College London (UCL), noted that “clinical trials with experimental designs have found that antidepressants improve mental health-related quality of life.”

University College London

Bruce Jancin/MDedge News

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

Antidepressant use is not associated with significant improvement in health-related quality of life (HRQoL) in patients with depression, new research suggests.

Researchers who conducted the study admit this finding was unexpected, and outside experts say no firm conclusions can be drawn from the research.

“Of course we were surprised by the results,” first author Omar Almohammed, PharmD, PhD, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, told this news organization.

“We were expecting to see some positive impact with the use of antidepressant medications on the HRQoL measures when we compared these patients to patients that did not use antidepressant medications,” Dr. Almohammed said.

The study was published online  in PLOS ONE.
 

Controversial impact on quality of life

Depression is known to harm HRQoL. Despite evidence that antidepressants improve depressed mood, their effect on patients’ overall well-being and HRQoL remains controversial.

The researchers examined the effect of antidepressants on HRQoL in adults with depression using 11 years of data from the U.S. Medical Expenditures Panel Survey (MEPS), a large longitudinal survey that tracks health service use in the United States. HRQoL was measured using the 12-item Short Form Health Survey (SF-12).

On average, about 17.5 million adults were diagnosed with depression each year during the study period (2005-2016). More than half (57.6%) of these patients were treated with antidepressants.

Patients with depression had an average age of 48.3 years. Women made up more than two-thirds of the total sample (68%), and more women than men received antidepressants (61% vs. 52%).

Compared with no antidepressant use, antidepressant use was associated with some improvement on the mental, but not physical, component of the SF-12, the researchers report.

However, difference-in-differences (D-I-D) univariate analysis showed no significant difference between adults using and not using antidepressants in the SF-12 physical (-0.35 vs. -0.34; P = .9,595) or mental component (1.28 vs. 1.13; P = .6,405).

“The multivariate D-I-D analyses ensured the robustness of these results,” the researchers note.

The change in HRQoL observed in patients using antidepressants was not significantly different from that seen among peers not using these drugs, the researchers report.

“We are not saying that antidepressant medications are not helpful at all; HRQoL is only one of many measures intended to assess health outcomes,” Dr. Almohammed told this news organization.

“Based on our research design and data, we can only say that patients who used antidepressant medications did not experience better change in terms of HRQoL compared to patients who did not use antidepressant medications,” he said.

“These patients may have had some improvement on other clinical outcome measures, but that clinical improvement did not have a significant positive impact on HRQoL,” he noted.

“We still recommend that patients continue using their antidepressant medications, but they may want to ask their doctors to provide them with other nonpharmacologic interventions as this may have additional impact on their HRQoL,” Dr. Almohammed said.

Further research is needed to address a “gap in knowledge” about the impact of nondrug interventions – alone or in combination with antidepressant medications – on patients’ HRQoL, Dr. Almohammed added.
 

Experts weigh in

Several experts weighed in on the study in a statement from the British nonprofit Science Media Center.

Gemma Lewis, PhD, with University College London (UCL), noted that “clinical trials with experimental designs have found that antidepressants improve mental health-related quality of life.”

University College London

Bruce Jancin/MDedge News

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

People aged 65 or older with human immunodeficiency virus (HIV) receive significantly more nonantiretroviral therapy (non-ART) medications, compared with patients with HIV who are between ages 50 and 64, according to a new study.

Moreover, in a sample of more than 900 patients with HIV, about 60% were taking at least one potentially inappropriate medication (PIM).

“Clinicians looking after persons living with HIV need to provide medication reconciliation with prioritization of medications based on the patients’ wishes and patients’ goals and life expectancy,” lead author Jacqueline McMillan, MD, clinical assistant professor of geriatric medicine at the University of Calgary (Alt.) told this news organization.

The findings were published online in the Canadian Journal of General Internal Medicine.
 

Examining the pill burden

A geriatrician by training and a clinical researcher with an interest in aging in patients with HIV, Dr. McMillan said she began to observe that many older adults with HIV were on polypharmacy. “There are many other things that aging people with HIV experience, such as frailty, falls, cognitive impairment, medication nonadherence, and mortality, but in this study, we focused just on the polypharmacy,” said Dr. McMillan.

Her aim was to see if there was a way to improve the pill burden in these older adults.

“Do they need to be on all of these medications? Is there anything that we were overprescribing that they no longer needed, or possibly not prescribing and undertreating people because they were older? I wanted to have a better sense that the medications we were prescribing were appropriate and that we minimized the pill burden for older adults,” Dr. McMillan said.

Persons with HIV are at a particularly increased risk of polypharmacy and potential drug-drug interactions because they need antiretroviral therapy medications and medications to treat comorbidities.

“Certainly, when the ARTs were first discovered, sometimes that regimen required several pills a day, but as time has gone on and our retrovirals have gotten better, some of those requirements have narrowed down to one-pill-a-day regimens. We are now replacing that pill burden with non-HIV drugs,” said Dr. McMillan.

The researchers obtained medication reconciliation data for 951 persons with HIV aged 50 or older as of Feb. 1, 2020. The study population was receiving HIV care through the Southern Alberta HIV Clinic in Calgary. The researchers defined polypharmacy as taking five or more non-ART drugs. They defined PIMs according to the 2019 Beers criteria.

In their analysis, the researchers compared patients aged 65 or older with patients aged 50-64, as well as patients with shorter (< 10 years) and longer (> 10 years) duration of HIV infection.
 

PIM use common

The population’s mean age was 59 years, and 82% were men. The mean time since HIV diagnosis was 17.8 years, and the median time was 17 years. Most (80%) of the patients were aged 50-64 years, and 20% were 65 and older.

The researchers collected sociodemographic, clinical, medication, and laboratory data for all patients at each clinical visit.

The mean number of non-ART medications was 6.7 for the population. Patients aged 65 years or older were taking significantly more non-ART medications than patients aged 50-64 (8.4 vs. 6.3; P < .001).

Similarly, those living with HIV for more than 10 years were taking significantly more non-ART medications (mean, 6.9) than those living with HIV for 10 or fewer years (mean 6.1; P = .0168).

In all, almost 60% of patients were taking at least one PIM. The mean number of PIMs per patient was 1.6.

Patients living with diagnosed HIV infection for more than 10 years were at greater risk of PIMs (1.6 PIMs) than those with shorter duration of HIV diagnosis (1.4 PIMs; P = .06).

Dr. McMillan says she hopes her study reminds clinicians to review patients’ medications at each visit and ensure they are neither over- nor underprescribing.

“From my perspective as a geriatrician, I hope that we do more dedicated medication reconciliation to actually make sure we know what people are taking,” she said. She asks patients to bring all their medications to the office so that they can review which ones match their diagnoses.

“I want to do more patient-centered personalized care for older adults, with a focus on people who are frail and who may have a limited life expectancy, so that we don’t have someone with a short life expectancy still taking 15 medications a day,” said Dr. McMillan.
 

‘Carefully document medications’

“This study identifies potentially inappropriate medication use in a group of older people living with HIV who are particularly vulnerable to it at an earlier age because of their medical complexity or frailty than perhaps healthy older adults,” Adrian Wagg, MD, professor of healthy aging in the department of medicine at the University of Alberta, Edmonton, told this news organization.

The study emphasizes the importance of careful documentation of medications that the patient is taking at every clinical visit, he said.

“Make sure you carefully document medications which are taken whenever you see the individual. Also try to limit the number of prescribers, because we know multiple prescribers are associated with greater likelihood of inappropriate prescribing,” Dr. Wagg said.

The move to wean patients from inappropriate medications is gaining momentum, he added.

“There is a huge movement now around actively deprescribing medications which are either no longer indicated or potentially of little benefit, given remaining life expectancy,” said Dr. Wagg. Drugs such as proton pump inhibitors, hypnotics, unrequired antidepressants, and benzodiazepines are the first targets for elimination, he concluded.

The study was funded by the University of Calgary. Dr. McMillan and Dr. Wagg reported no relevant financial relationships.

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

People aged 65 or older with human immunodeficiency virus (HIV) receive significantly more nonantiretroviral therapy (non-ART) medications, compared with patients with HIV who are between ages 50 and 64, according to a new study.

Moreover, in a sample of more than 900 patients with HIV, about 60% were taking at least one potentially inappropriate medication (PIM).

“Clinicians looking after persons living with HIV need to provide medication reconciliation with prioritization of medications based on the patients’ wishes and patients’ goals and life expectancy,” lead author Jacqueline McMillan, MD, clinical assistant professor of geriatric medicine at the University of Calgary (Alt.) told this news organization.

The findings were published online in the Canadian Journal of General Internal Medicine.
 

Examining the pill burden

A geriatrician by training and a clinical researcher with an interest in aging in patients with HIV, Dr. McMillan said she began to observe that many older adults with HIV were on polypharmacy. “There are many other things that aging people with HIV experience, such as frailty, falls, cognitive impairment, medication nonadherence, and mortality, but in this study, we focused just on the polypharmacy,” said Dr. McMillan.

Her aim was to see if there was a way to improve the pill burden in these older adults.

“Do they need to be on all of these medications? Is there anything that we were overprescribing that they no longer needed, or possibly not prescribing and undertreating people because they were older? I wanted to have a better sense that the medications we were prescribing were appropriate and that we minimized the pill burden for older adults,” Dr. McMillan said.

Persons with HIV are at a particularly increased risk of polypharmacy and potential drug-drug interactions because they need antiretroviral therapy medications and medications to treat comorbidities.

“Certainly, when the ARTs were first discovered, sometimes that regimen required several pills a day, but as time has gone on and our retrovirals have gotten better, some of those requirements have narrowed down to one-pill-a-day regimens. We are now replacing that pill burden with non-HIV drugs,” said Dr. McMillan.

The researchers obtained medication reconciliation data for 951 persons with HIV aged 50 or older as of Feb. 1, 2020. The study population was receiving HIV care through the Southern Alberta HIV Clinic in Calgary. The researchers defined polypharmacy as taking five or more non-ART drugs. They defined PIMs according to the 2019 Beers criteria.

In their analysis, the researchers compared patients aged 65 or older with patients aged 50-64, as well as patients with shorter (< 10 years) and longer (> 10 years) duration of HIV infection.
 

PIM use common

The population’s mean age was 59 years, and 82% were men. The mean time since HIV diagnosis was 17.8 years, and the median time was 17 years. Most (80%) of the patients were aged 50-64 years, and 20% were 65 and older.

The researchers collected sociodemographic, clinical, medication, and laboratory data for all patients at each clinical visit.

The mean number of non-ART medications was 6.7 for the population. Patients aged 65 years or older were taking significantly more non-ART medications than patients aged 50-64 (8.4 vs. 6.3; P < .001).

Similarly, those living with HIV for more than 10 years were taking significantly more non-ART medications (mean, 6.9) than those living with HIV for 10 or fewer years (mean 6.1; P = .0168).

In all, almost 60% of patients were taking at least one PIM. The mean number of PIMs per patient was 1.6.

Patients living with diagnosed HIV infection for more than 10 years were at greater risk of PIMs (1.6 PIMs) than those with shorter duration of HIV diagnosis (1.4 PIMs; P = .06).

Dr. McMillan says she hopes her study reminds clinicians to review patients’ medications at each visit and ensure they are neither over- nor underprescribing.

“From my perspective as a geriatrician, I hope that we do more dedicated medication reconciliation to actually make sure we know what people are taking,” she said. She asks patients to bring all their medications to the office so that they can review which ones match their diagnoses.

“I want to do more patient-centered personalized care for older adults, with a focus on people who are frail and who may have a limited life expectancy, so that we don’t have someone with a short life expectancy still taking 15 medications a day,” said Dr. McMillan.
 

‘Carefully document medications’

“This study identifies potentially inappropriate medication use in a group of older people living with HIV who are particularly vulnerable to it at an earlier age because of their medical complexity or frailty than perhaps healthy older adults,” Adrian Wagg, MD, professor of healthy aging in the department of medicine at the University of Alberta, Edmonton, told this news organization.

The study emphasizes the importance of careful documentation of medications that the patient is taking at every clinical visit, he said.

“Make sure you carefully document medications which are taken whenever you see the individual. Also try to limit the number of prescribers, because we know multiple prescribers are associated with greater likelihood of inappropriate prescribing,” Dr. Wagg said.

The move to wean patients from inappropriate medications is gaining momentum, he added.

“There is a huge movement now around actively deprescribing medications which are either no longer indicated or potentially of little benefit, given remaining life expectancy,” said Dr. Wagg. Drugs such as proton pump inhibitors, hypnotics, unrequired antidepressants, and benzodiazepines are the first targets for elimination, he concluded.

The study was funded by the University of Calgary. Dr. McMillan and Dr. Wagg reported no relevant financial relationships.

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

People aged 65 or older with human immunodeficiency virus (HIV) receive significantly more nonantiretroviral therapy (non-ART) medications, compared with patients with HIV who are between ages 50 and 64, according to a new study.

Moreover, in a sample of more than 900 patients with HIV, about 60% were taking at least one potentially inappropriate medication (PIM).

“Clinicians looking after persons living with HIV need to provide medication reconciliation with prioritization of medications based on the patients’ wishes and patients’ goals and life expectancy,” lead author Jacqueline McMillan, MD, clinical assistant professor of geriatric medicine at the University of Calgary (Alt.) told this news organization.

The findings were published online in the Canadian Journal of General Internal Medicine.
 

Examining the pill burden

A geriatrician by training and a clinical researcher with an interest in aging in patients with HIV, Dr. McMillan said she began to observe that many older adults with HIV were on polypharmacy. “There are many other things that aging people with HIV experience, such as frailty, falls, cognitive impairment, medication nonadherence, and mortality, but in this study, we focused just on the polypharmacy,” said Dr. McMillan.

Her aim was to see if there was a way to improve the pill burden in these older adults.

“Do they need to be on all of these medications? Is there anything that we were overprescribing that they no longer needed, or possibly not prescribing and undertreating people because they were older? I wanted to have a better sense that the medications we were prescribing were appropriate and that we minimized the pill burden for older adults,” Dr. McMillan said.

Persons with HIV are at a particularly increased risk of polypharmacy and potential drug-drug interactions because they need antiretroviral therapy medications and medications to treat comorbidities.

“Certainly, when the ARTs were first discovered, sometimes that regimen required several pills a day, but as time has gone on and our retrovirals have gotten better, some of those requirements have narrowed down to one-pill-a-day regimens. We are now replacing that pill burden with non-HIV drugs,” said Dr. McMillan.

The researchers obtained medication reconciliation data for 951 persons with HIV aged 50 or older as of Feb. 1, 2020. The study population was receiving HIV care through the Southern Alberta HIV Clinic in Calgary. The researchers defined polypharmacy as taking five or more non-ART drugs. They defined PIMs according to the 2019 Beers criteria.

In their analysis, the researchers compared patients aged 65 or older with patients aged 50-64, as well as patients with shorter (< 10 years) and longer (> 10 years) duration of HIV infection.
 

PIM use common

The population’s mean age was 59 years, and 82% were men. The mean time since HIV diagnosis was 17.8 years, and the median time was 17 years. Most (80%) of the patients were aged 50-64 years, and 20% were 65 and older.

The researchers collected sociodemographic, clinical, medication, and laboratory data for all patients at each clinical visit.

The mean number of non-ART medications was 6.7 for the population. Patients aged 65 years or older were taking significantly more non-ART medications than patients aged 50-64 (8.4 vs. 6.3; P < .001).

Similarly, those living with HIV for more than 10 years were taking significantly more non-ART medications (mean, 6.9) than those living with HIV for 10 or fewer years (mean 6.1; P = .0168).

In all, almost 60% of patients were taking at least one PIM. The mean number of PIMs per patient was 1.6.

Patients living with diagnosed HIV infection for more than 10 years were at greater risk of PIMs (1.6 PIMs) than those with shorter duration of HIV diagnosis (1.4 PIMs; P = .06).

Dr. McMillan says she hopes her study reminds clinicians to review patients’ medications at each visit and ensure they are neither over- nor underprescribing.

“From my perspective as a geriatrician, I hope that we do more dedicated medication reconciliation to actually make sure we know what people are taking,” she said. She asks patients to bring all their medications to the office so that they can review which ones match their diagnoses.

“I want to do more patient-centered personalized care for older adults, with a focus on people who are frail and who may have a limited life expectancy, so that we don’t have someone with a short life expectancy still taking 15 medications a day,” said Dr. McMillan.
 

‘Carefully document medications’

“This study identifies potentially inappropriate medication use in a group of older people living with HIV who are particularly vulnerable to it at an earlier age because of their medical complexity or frailty than perhaps healthy older adults,” Adrian Wagg, MD, professor of healthy aging in the department of medicine at the University of Alberta, Edmonton, told this news organization.

The study emphasizes the importance of careful documentation of medications that the patient is taking at every clinical visit, he said.

“Make sure you carefully document medications which are taken whenever you see the individual. Also try to limit the number of prescribers, because we know multiple prescribers are associated with greater likelihood of inappropriate prescribing,” Dr. Wagg said.

The move to wean patients from inappropriate medications is gaining momentum, he added.

“There is a huge movement now around actively deprescribing medications which are either no longer indicated or potentially of little benefit, given remaining life expectancy,” said Dr. Wagg. Drugs such as proton pump inhibitors, hypnotics, unrequired antidepressants, and benzodiazepines are the first targets for elimination, he concluded.

The study was funded by the University of Calgary. Dr. McMillan and Dr. Wagg reported no relevant financial relationships.

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

BOSTON – When patients present with complaints of hair loss or changes in hair color or texture, make sure to ask if they are taking oral hair growth supplements.

This is an important question because patients consider supplements as “natural and healthy,” not as drugs or chemicals, Wilma F. Bergfeld, MD, said at the annual meeting of the American Academy of Dermatology.

Some of these products contain botanicals, which are not always safe, added Dr. Bergfeld, professor of dermatology and pathology at the Cleveland Clinic. “They have many activities, and they are being touted as having some activity in helping the hair or enhancing hair growth,” including having 5-alpha-reductase inhibitors as an ingredient. “Saw palmetto is probably the most common one, but there are a host of natural ingredients that are being put into these supplements, including those that promote androgen induction, as well as antioxidants and anti-inflammatories.”

In the opinion of Dr. Bergfeld, a nutrition-focused physical assessment should include an examination of the scalp and all hairy areas. “It’s also important to see the symmetry and shape of hair growth or hair loss areas, the distribution, hair color, the thickness and texture of the hair fibers,” she added.

Besides asking about what supplements patients are taking, other questions to ask during the visit include: Are you noticing more hair on your brush, pillow, and shoulders, or in the shower? Do you think your hair is thinning? What are your medical problems? Have you experienced rapid weight loss? Have you started any new medications? What medication(s) are you on? What foods do you eat? Do you have a family history of hair loss?

Possible causes of hair loss or changes include environmental factors, stress, hormonal changes, medications, and nutrition.

Common ingredients contained in healthy hair supplements include biotin, folic acid, L-cysteine, L-methionine, MSM (methylsulfonylmethane), vitamin B complex, and vitamins A, C, D, and E. “Vitamin D and A are associated on the hair follicle receptor sites, and they balance each other, so if one is down the other is usually down,” said Dr. Bergfeld, who directs Cleveland Clinic’s hair disorders clinic and its dermatopathology program. Other important ingredients include iron, zinc, manganese, amino acids including L-Lysine, and fatty acids.

Iron deficiency is a known cause of hair loss. “The absorption of iron relies on vitamin C and sometimes lysine,” she said. Red meat has a high iron content and since many patients are restricting red meat intake, “they do need to think about that.” Zinc deficiency is less common in Western countries, she continued, “but when you find it, it’s revolutionary because if they’re shedding hair and their hair character is changing, often some supplementation will do the trick. But remember: Zinc is not only an anti-inflammatory, it’s also an antiandrogen. It has 5-alpha-reductase inhibitor capabilities.”.

Dr. Bergfeld noted that biotin, also known as vitamin B₇ and found in many foods, is used in many vitamin supplements marketed for hair loss. The recommended daily allowance (RDA) is 30 mcg/day in adults but the amount in hair supplements can be up to 650% of RDA. “Biotin at high levels is believed to be safe, but can interfere with troponin and other lab testing,” she cautioned. “This can lead to dangerous false laboratory results.”

To date, insufficient data exist to recommend supplementation with zinc, riboflavin, folic acid, or vitamin B₁₂ for hair loss, “but they may help in cases of deficiency,” said Dr. Bergfeld, a past president of the American Hair Research Society. The use of vitamin E and biotin supplementation is not supported in the literature for treating androgenetic alopecia or telogen effluvium. Excessive vitamin A (not beta carotene) and selenium can contribute to hair loss and studies have shown a relationship between androgenetic alopecia and low vitamin D levels. “Vitamin D should be supplemented if serum levels are low, but more studies are needed to determine the effect of iron and zinc supplementation” in patients with androgenetic alopecia, she said.

While there are not enough data to support a recommendation for supplementation of folic or B₁₂ for alopecia, she said, “vitamin B₁₂ deficiency may occur in androgenetic alopecia patients, associated with pernicious anemia.”

She added that the use biotin supplementation for the treatment of androgenetic alopecia is not supported by available data, and “it is also unclear if selenium plays a role in this disease.”

Dr. Bergfeld reported having no disclosures related to her presentation.

BOSTON – When patients present with complaints of hair loss or changes in hair color or texture, make sure to ask if they are taking oral hair growth supplements.

This is an important question because patients consider supplements as “natural and healthy,” not as drugs or chemicals, Wilma F. Bergfeld, MD, said at the annual meeting of the American Academy of Dermatology.

Some of these products contain botanicals, which are not always safe, added Dr. Bergfeld, professor of dermatology and pathology at the Cleveland Clinic. “They have many activities, and they are being touted as having some activity in helping the hair or enhancing hair growth,” including having 5-alpha-reductase inhibitors as an ingredient. “Saw palmetto is probably the most common one, but there are a host of natural ingredients that are being put into these supplements, including those that promote androgen induction, as well as antioxidants and anti-inflammatories.”

In the opinion of Dr. Bergfeld, a nutrition-focused physical assessment should include an examination of the scalp and all hairy areas. “It’s also important to see the symmetry and shape of hair growth or hair loss areas, the distribution, hair color, the thickness and texture of the hair fibers,” she added.

Besides asking about what supplements patients are taking, other questions to ask during the visit include: Are you noticing more hair on your brush, pillow, and shoulders, or in the shower? Do you think your hair is thinning? What are your medical problems? Have you experienced rapid weight loss? Have you started any new medications? What medication(s) are you on? What foods do you eat? Do you have a family history of hair loss?

Possible causes of hair loss or changes include environmental factors, stress, hormonal changes, medications, and nutrition.

Common ingredients contained in healthy hair supplements include biotin, folic acid, L-cysteine, L-methionine, MSM (methylsulfonylmethane), vitamin B complex, and vitamins A, C, D, and E. “Vitamin D and A are associated on the hair follicle receptor sites, and they balance each other, so if one is down the other is usually down,” said Dr. Bergfeld, who directs Cleveland Clinic’s hair disorders clinic and its dermatopathology program. Other important ingredients include iron, zinc, manganese, amino acids including L-Lysine, and fatty acids.

Iron deficiency is a known cause of hair loss. “The absorption of iron relies on vitamin C and sometimes lysine,” she said. Red meat has a high iron content and since many patients are restricting red meat intake, “they do need to think about that.” Zinc deficiency is less common in Western countries, she continued, “but when you find it, it’s revolutionary because if they’re shedding hair and their hair character is changing, often some supplementation will do the trick. But remember: Zinc is not only an anti-inflammatory, it’s also an antiandrogen. It has 5-alpha-reductase inhibitor capabilities.”.

Dr. Bergfeld noted that biotin, also known as vitamin B₇ and found in many foods, is used in many vitamin supplements marketed for hair loss. The recommended daily allowance (RDA) is 30 mcg/day in adults but the amount in hair supplements can be up to 650% of RDA. “Biotin at high levels is believed to be safe, but can interfere with troponin and other lab testing,” she cautioned. “This can lead to dangerous false laboratory results.”

To date, insufficient data exist to recommend supplementation with zinc, riboflavin, folic acid, or vitamin B₁₂ for hair loss, “but they may help in cases of deficiency,” said Dr. Bergfeld, a past president of the American Hair Research Society. The use of vitamin E and biotin supplementation is not supported in the literature for treating androgenetic alopecia or telogen effluvium. Excessive vitamin A (not beta carotene) and selenium can contribute to hair loss and studies have shown a relationship between androgenetic alopecia and low vitamin D levels. “Vitamin D should be supplemented if serum levels are low, but more studies are needed to determine the effect of iron and zinc supplementation” in patients with androgenetic alopecia, she said.

While there are not enough data to support a recommendation for supplementation of folic or B₁₂ for alopecia, she said, “vitamin B₁₂ deficiency may occur in androgenetic alopecia patients, associated with pernicious anemia.”

She added that the use biotin supplementation for the treatment of androgenetic alopecia is not supported by available data, and “it is also unclear if selenium plays a role in this disease.”

Dr. Bergfeld reported having no disclosures related to her presentation.

BOSTON – When patients present with complaints of hair loss or changes in hair color or texture, make sure to ask if they are taking oral hair growth supplements.

This is an important question because patients consider supplements as “natural and healthy,” not as drugs or chemicals, Wilma F. Bergfeld, MD, said at the annual meeting of the American Academy of Dermatology.

Some of these products contain botanicals, which are not always safe, added Dr. Bergfeld, professor of dermatology and pathology at the Cleveland Clinic. “They have many activities, and they are being touted as having some activity in helping the hair or enhancing hair growth,” including having 5-alpha-reductase inhibitors as an ingredient. “Saw palmetto is probably the most common one, but there are a host of natural ingredients that are being put into these supplements, including those that promote androgen induction, as well as antioxidants and anti-inflammatories.”

In the opinion of Dr. Bergfeld, a nutrition-focused physical assessment should include an examination of the scalp and all hairy areas. “It’s also important to see the symmetry and shape of hair growth or hair loss areas, the distribution, hair color, the thickness and texture of the hair fibers,” she added.

Besides asking about what supplements patients are taking, other questions to ask during the visit include: Are you noticing more hair on your brush, pillow, and shoulders, or in the shower? Do you think your hair is thinning? What are your medical problems? Have you experienced rapid weight loss? Have you started any new medications? What medication(s) are you on? What foods do you eat? Do you have a family history of hair loss?

Possible causes of hair loss or changes include environmental factors, stress, hormonal changes, medications, and nutrition.

Common ingredients contained in healthy hair supplements include biotin, folic acid, L-cysteine, L-methionine, MSM (methylsulfonylmethane), vitamin B complex, and vitamins A, C, D, and E. “Vitamin D and A are associated on the hair follicle receptor sites, and they balance each other, so if one is down the other is usually down,” said Dr. Bergfeld, who directs Cleveland Clinic’s hair disorders clinic and its dermatopathology program. Other important ingredients include iron, zinc, manganese, amino acids including L-Lysine, and fatty acids.

Iron deficiency is a known cause of hair loss. “The absorption of iron relies on vitamin C and sometimes lysine,” she said. Red meat has a high iron content and since many patients are restricting red meat intake, “they do need to think about that.” Zinc deficiency is less common in Western countries, she continued, “but when you find it, it’s revolutionary because if they’re shedding hair and their hair character is changing, often some supplementation will do the trick. But remember: Zinc is not only an anti-inflammatory, it’s also an antiandrogen. It has 5-alpha-reductase inhibitor capabilities.”.

Dr. Bergfeld noted that biotin, also known as vitamin B₇ and found in many foods, is used in many vitamin supplements marketed for hair loss. The recommended daily allowance (RDA) is 30 mcg/day in adults but the amount in hair supplements can be up to 650% of RDA. “Biotin at high levels is believed to be safe, but can interfere with troponin and other lab testing,” she cautioned. “This can lead to dangerous false laboratory results.”

To date, insufficient data exist to recommend supplementation with zinc, riboflavin, folic acid, or vitamin B₁₂ for hair loss, “but they may help in cases of deficiency,” said Dr. Bergfeld, a past president of the American Hair Research Society. The use of vitamin E and biotin supplementation is not supported in the literature for treating androgenetic alopecia or telogen effluvium. Excessive vitamin A (not beta carotene) and selenium can contribute to hair loss and studies have shown a relationship between androgenetic alopecia and low vitamin D levels. “Vitamin D should be supplemented if serum levels are low, but more studies are needed to determine the effect of iron and zinc supplementation” in patients with androgenetic alopecia, she said.

While there are not enough data to support a recommendation for supplementation of folic or B₁₂ for alopecia, she said, “vitamin B₁₂ deficiency may occur in androgenetic alopecia patients, associated with pernicious anemia.”

She added that the use biotin supplementation for the treatment of androgenetic alopecia is not supported by available data, and “it is also unclear if selenium plays a role in this disease.”

Dr. Bergfeld reported having no disclosures related to her presentation.

High rates of antipsychotic switching in first episode psychosis (FEP) suggests first-line prescribing is less than optimal and does not follow recent clinical guidance.

In a large-scale, real-world analysis of U.K. prescribing patterns, researchers found more than two-thirds of patients who received antipsychotics for FEP switched medication, and almost half switched drugs three times.

VladimirSorokin/Getty Images

Although this is “one of the largest real-world studies examining antipsychotic treatment strategies,” it reflects findings from previous, smaller studies showing “antipsychotic switching in first episode psychosis is high,” said study investigator Aimee Brinn, Institute of Psychiatry, Psychology & Neuroscience at King’s College London.

This may reflect reports of poor efficacy and suggests that first-line prescribing is “suboptimal,” Ms. Brinn noted. In addition, olanzapine remains the most popular antipsychotic for prescribing despite recent guidelines indicating it is “not ideal ... due to its dangerous metabolic side effects,” she added.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.
 

Real-world data

The response to, and tolerability of, antipsychotics differs between patients with FEP; and prescribing patterns “reflect clinician and patient-led decisionmaking,” Ms. Brinn told meeting attendees.

Since randomized controlled trials “do not necessarily reflect prescribing practice in real-world clinical settings,” the researchers gathered data from a large mental health care electronic health record dataset.

The investigators examined records from the South London and Maudsley NHS Foundation Trust (SLaM), which has a catchment area of 1.2 million individuals across four boroughs of London. The group sees approximately 37,500 active patients per week.

The team used the Clinical Interactive Record Search tool to extract data on 2,309 adults with FEP who received care from a SLaM early intervention in psychosis service between April 1, 2008, and March 31, 2019.

They found that 12 different antipsychotics were prescribed as first-line treatment. The most common were olanzapine (43.9%), risperidone (24.7%), and aripiprazole (19.9%).

Results showed that over 81,969.5 person-years of follow-up, at a minimum of 24 months per patient, 68.8% had an antipsychotic switch. The most common first treatment switch, in 17.9% of patients, was from olanzapine to aripiprazole.

Of patients who switched to aripiprazole, 48.4% stayed on the drug, 26% switched back to olanzapine, and 25.6% received other treatment. Overall, 44.7% of patients switched medication at least three times.

Among patients with FEP who did not switch, 42.2% were prescribed olanzapine, 26.2% risperidone, 23.3% aripiprazole, 5.6% quetiapine, and 2.7% amisulpride.

During the post-presentation discussion, Ms. Brinn was asked whether the high rate of first-line olanzapine prescribing could be because patients started treatment as inpatients and were then switched once they were moved to community care.

“We found that a lot of patients would be prescribed olanzapine for around 7 days at the start of their prescription and then switch,” Ms. Brinn said, adding it is “likely” they started as inpatients. The investigators are currently examining the differences between inpatient and outpatient prescriptions to verify whether this is indeed the case, she added.
 

‘Pulling out the big guns too fast?’

Commenting on the findings, Thomas W. Sedlak, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, said the study raises a “number of questions.”

Both olanzapine and risperidone “tend to have higher treatment effect improvements than aripiprazole, so it’s curious that a switch to aripiprazole was common,” said Dr. Sedlak, who was not involved with the research.

“Are we pulling out the ‘big guns’ too fast, or inappropriately, especially as olanzapine and risperidone carry greater risk of weight gain?” he asked. In addition, “now that olanzapine is available with samidorphan to mitigate weight gain, will that shape future patterns, if it can be paid for?”

Dr. Sedlak noted it was unclear why olanzapine was chosen so often as first-line treatment in the study and agreed it is “possible that hospitalized patients had been prescribed a ‘stronger’ medication like olanzapine compared to never-hospitalized patients.”

He also underlined that it is “not clear if patients in this FEP program are representative of all FEP patients.”

“For instance, if the program is well known to inpatient hospital social workers, then the program might be disproportionately filled with patients who have had more severe symptoms,” Dr. Sedlak said.

The study was supported by Janssen-Cilag. The investigators and Dr. Sedlak have disclosed no relevant financial relationships.

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

High rates of antipsychotic switching in first episode psychosis (FEP) suggests first-line prescribing is less than optimal and does not follow recent clinical guidance.

In a large-scale, real-world analysis of U.K. prescribing patterns, researchers found more than two-thirds of patients who received antipsychotics for FEP switched medication, and almost half switched drugs three times.

VladimirSorokin/Getty Images

Although this is “one of the largest real-world studies examining antipsychotic treatment strategies,” it reflects findings from previous, smaller studies showing “antipsychotic switching in first episode psychosis is high,” said study investigator Aimee Brinn, Institute of Psychiatry, Psychology & Neuroscience at King’s College London.

This may reflect reports of poor efficacy and suggests that first-line prescribing is “suboptimal,” Ms. Brinn noted. In addition, olanzapine remains the most popular antipsychotic for prescribing despite recent guidelines indicating it is “not ideal ... due to its dangerous metabolic side effects,” she added.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.
 

Real-world data

The response to, and tolerability of, antipsychotics differs between patients with FEP; and prescribing patterns “reflect clinician and patient-led decisionmaking,” Ms. Brinn told meeting attendees.

Since randomized controlled trials “do not necessarily reflect prescribing practice in real-world clinical settings,” the researchers gathered data from a large mental health care electronic health record dataset.

The investigators examined records from the South London and Maudsley NHS Foundation Trust (SLaM), which has a catchment area of 1.2 million individuals across four boroughs of London. The group sees approximately 37,500 active patients per week.

The team used the Clinical Interactive Record Search tool to extract data on 2,309 adults with FEP who received care from a SLaM early intervention in psychosis service between April 1, 2008, and March 31, 2019.

They found that 12 different antipsychotics were prescribed as first-line treatment. The most common were olanzapine (43.9%), risperidone (24.7%), and aripiprazole (19.9%).

Results showed that over 81,969.5 person-years of follow-up, at a minimum of 24 months per patient, 68.8% had an antipsychotic switch. The most common first treatment switch, in 17.9% of patients, was from olanzapine to aripiprazole.

Of patients who switched to aripiprazole, 48.4% stayed on the drug, 26% switched back to olanzapine, and 25.6% received other treatment. Overall, 44.7% of patients switched medication at least three times.

Among patients with FEP who did not switch, 42.2% were prescribed olanzapine, 26.2% risperidone, 23.3% aripiprazole, 5.6% quetiapine, and 2.7% amisulpride.

During the post-presentation discussion, Ms. Brinn was asked whether the high rate of first-line olanzapine prescribing could be because patients started treatment as inpatients and were then switched once they were moved to community care.

“We found that a lot of patients would be prescribed olanzapine for around 7 days at the start of their prescription and then switch,” Ms. Brinn said, adding it is “likely” they started as inpatients. The investigators are currently examining the differences between inpatient and outpatient prescriptions to verify whether this is indeed the case, she added.
 

‘Pulling out the big guns too fast?’

Commenting on the findings, Thomas W. Sedlak, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, said the study raises a “number of questions.”

Both olanzapine and risperidone “tend to have higher treatment effect improvements than aripiprazole, so it’s curious that a switch to aripiprazole was common,” said Dr. Sedlak, who was not involved with the research.

“Are we pulling out the ‘big guns’ too fast, or inappropriately, especially as olanzapine and risperidone carry greater risk of weight gain?” he asked. In addition, “now that olanzapine is available with samidorphan to mitigate weight gain, will that shape future patterns, if it can be paid for?”

Dr. Sedlak noted it was unclear why olanzapine was chosen so often as first-line treatment in the study and agreed it is “possible that hospitalized patients had been prescribed a ‘stronger’ medication like olanzapine compared to never-hospitalized patients.”

He also underlined that it is “not clear if patients in this FEP program are representative of all FEP patients.”

“For instance, if the program is well known to inpatient hospital social workers, then the program might be disproportionately filled with patients who have had more severe symptoms,” Dr. Sedlak said.

The study was supported by Janssen-Cilag. The investigators and Dr. Sedlak have disclosed no relevant financial relationships.

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

High rates of antipsychotic switching in first episode psychosis (FEP) suggests first-line prescribing is less than optimal and does not follow recent clinical guidance.

In a large-scale, real-world analysis of U.K. prescribing patterns, researchers found more than two-thirds of patients who received antipsychotics for FEP switched medication, and almost half switched drugs three times.

VladimirSorokin/Getty Images

Although this is “one of the largest real-world studies examining antipsychotic treatment strategies,” it reflects findings from previous, smaller studies showing “antipsychotic switching in first episode psychosis is high,” said study investigator Aimee Brinn, Institute of Psychiatry, Psychology & Neuroscience at King’s College London.

This may reflect reports of poor efficacy and suggests that first-line prescribing is “suboptimal,” Ms. Brinn noted. In addition, olanzapine remains the most popular antipsychotic for prescribing despite recent guidelines indicating it is “not ideal ... due to its dangerous metabolic side effects,” she added.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.
 

Real-world data

The response to, and tolerability of, antipsychotics differs between patients with FEP; and prescribing patterns “reflect clinician and patient-led decisionmaking,” Ms. Brinn told meeting attendees.

Since randomized controlled trials “do not necessarily reflect prescribing practice in real-world clinical settings,” the researchers gathered data from a large mental health care electronic health record dataset.

The investigators examined records from the South London and Maudsley NHS Foundation Trust (SLaM), which has a catchment area of 1.2 million individuals across four boroughs of London. The group sees approximately 37,500 active patients per week.

The team used the Clinical Interactive Record Search tool to extract data on 2,309 adults with FEP who received care from a SLaM early intervention in psychosis service between April 1, 2008, and March 31, 2019.

They found that 12 different antipsychotics were prescribed as first-line treatment. The most common were olanzapine (43.9%), risperidone (24.7%), and aripiprazole (19.9%).

Results showed that over 81,969.5 person-years of follow-up, at a minimum of 24 months per patient, 68.8% had an antipsychotic switch. The most common first treatment switch, in 17.9% of patients, was from olanzapine to aripiprazole.

Of patients who switched to aripiprazole, 48.4% stayed on the drug, 26% switched back to olanzapine, and 25.6% received other treatment. Overall, 44.7% of patients switched medication at least three times.

Among patients with FEP who did not switch, 42.2% were prescribed olanzapine, 26.2% risperidone, 23.3% aripiprazole, 5.6% quetiapine, and 2.7% amisulpride.

During the post-presentation discussion, Ms. Brinn was asked whether the high rate of first-line olanzapine prescribing could be because patients started treatment as inpatients and were then switched once they were moved to community care.

“We found that a lot of patients would be prescribed olanzapine for around 7 days at the start of their prescription and then switch,” Ms. Brinn said, adding it is “likely” they started as inpatients. The investigators are currently examining the differences between inpatient and outpatient prescriptions to verify whether this is indeed the case, she added.
 

‘Pulling out the big guns too fast?’

Commenting on the findings, Thomas W. Sedlak, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, said the study raises a “number of questions.”

Both olanzapine and risperidone “tend to have higher treatment effect improvements than aripiprazole, so it’s curious that a switch to aripiprazole was common,” said Dr. Sedlak, who was not involved with the research.

“Are we pulling out the ‘big guns’ too fast, or inappropriately, especially as olanzapine and risperidone carry greater risk of weight gain?” he asked. In addition, “now that olanzapine is available with samidorphan to mitigate weight gain, will that shape future patterns, if it can be paid for?”

Dr. Sedlak noted it was unclear why olanzapine was chosen so often as first-line treatment in the study and agreed it is “possible that hospitalized patients had been prescribed a ‘stronger’ medication like olanzapine compared to never-hospitalized patients.”

He also underlined that it is “not clear if patients in this FEP program are representative of all FEP patients.”

“For instance, if the program is well known to inpatient hospital social workers, then the program might be disproportionately filled with patients who have had more severe symptoms,” Dr. Sedlak said.

The study was supported by Janssen-Cilag. The investigators and Dr. Sedlak have disclosed no relevant financial relationships.

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

NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further clinical data continue to show benefit from preoperative treatment with the immune checkpoint inhibitor nivolumab (Opdivo) with chemotherapy.

The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.

Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.

“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.

The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.

Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”

“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”

Importance of Neoadjuvant Immunotherapy

New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.

Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).

In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).

Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.

“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
 

Neoadjuvant slow to catch on

About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.

Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.

The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.

In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.

In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.

“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”

Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.

“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.
 

Fears of delaying surgery

In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.

“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”

In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
 

CheckMate 816 details

In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.

After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.

At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.

Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.

In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.

The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.

The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.

Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.

CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.

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

NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further clinical data continue to show benefit from preoperative treatment with the immune checkpoint inhibitor nivolumab (Opdivo) with chemotherapy.

The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.

Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.

“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.

The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.

Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”

“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”

Importance of Neoadjuvant Immunotherapy

New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.

Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).

In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).

Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.

“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
 

Neoadjuvant slow to catch on

About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.

Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.

The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.

In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.

In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.

“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”

Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.

“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.
 

Fears of delaying surgery

In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.

“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”

In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
 

CheckMate 816 details

In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.

After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.

At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.

Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.

In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.

The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.

The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.

Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.

CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.

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

NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further clinical data continue to show benefit from preoperative treatment with the immune checkpoint inhibitor nivolumab (Opdivo) with chemotherapy.

The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.

Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.

“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.

The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.

Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”

“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”

Importance of Neoadjuvant Immunotherapy

New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.

Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).

In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).

Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.

“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
 

Neoadjuvant slow to catch on

About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.

Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.

The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.

In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.

In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.

“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”

Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.

“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.
 

Fears of delaying surgery

In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.

“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”

In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
 

CheckMate 816 details

In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.

After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.

At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.

Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.

In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.

The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.

The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.

Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.

CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.

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

NEW ORLEANS – In just over one-third of patients with metastatic melanoma who had experienced disease progression while receiving multiple prior lines of therapy, including immunotherapy and targeted agents, objective clinical responses occurred with a customized cell therapy based on T cells extracted directly from tumor tissue.

The product, called lifileucel, is custom made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from tumor lesions. This approach differs from other cell-based therapies, such as chimeric antigen receptor (CAR) T cell therapy, which utilizes T cells collected from the patient’s blood.

The new results come from a phase 2 trial conducted in 66 patients with previously treated unresectable or metastatic melanoma who received a single dose of the product. The objective response rate was 36.4%.

“Lifileucel has demonstrated efficacy and durability of response for patients with metastatic melanoma and represents a viable therapeutic option warranting further investigation,” commented Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville (Ky.).

He presented the new data at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.

Customized cell therapy with TILs has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.

However, “generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells,” commented Philip Greenberg, MD, professor and head of the program in immunology in the Clinical Research Division of the Fred Hutchinson Cancer Center, Seattle, who was the invited discussant.

The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise. The patient-specific products are then disseminated to multiple centers, he said. The study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes.

“Toxicity was, however, significant, although it was generally manageable, and it did occur early, generally within the first 2 weeks,” he noted.
 

Patient-derived product

Lifileucel is a tailor-made immunotherapy product created from melanoma tumor tissues resected from lesions in skin, lymph nodes, liver, lung, peritoneum, musculoskeletal system, breast, or other visceral organs. The cells are shipped to a central manufacturing facility, whre the TILs are isolated, cultured, expanded, and reinvigorated. The cells are then harvested and cryopreserved. The process takes about 22 days. The cryopreserved product is then shipped back to the treating facility.

Prior to receiving the expanded and rejuvenated TILs, patients undergo myeloablative conditioning with cyclophosphamide followed by fludarabine. The TILs are then delivered in a single infusion, followed by administration of up to six doses of interleukin-2 (IL-2).
 

Details from clinical trial

At the meeting, Dr. Chesney reported details on the 66 patients in the trial. They had metastatic melanoma that was progressing on treatment. The mean number of prior lines of therapy was 3.3. All of the patients had received prior anti–programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1) agents; 53 had received a cytotoxic T lymphocyte protein 4 (CTLA-4) inhibitor; and 15 had received a BRAF/MEK inhibitor.

These patients had a mean of six baseline target and nontarget lesions, and 28 patients had liver and/or brain metastases.

Just over a third of patients (24 of 66, 36.4%) had an objective response; three patients had a complete response; and 21 had a partial response. In addition, 29 patients had stable disease, and nine experienced disease progression. Four patients had not undergone the first assessment at the time of data cutoff.

After a median follow-up of 28.1 months, the median duration of response was not reached. It ranged from 2.2 to > 35.2 months.

Since the data cutoff in April 2020, reduction of tumor burden has occurred in 50 of 62 evaluable patients. Reductions in the target lesion sum of diameters has occurred in 11 patients. In one patient, a partial response converted to a complete response 24 months after infusion, Dr. Chesney noted.

The mean number of TILs infused was 27.3 billion (27.3 x 109). Appropriate amounts of TILs were manufactured from tumor samples acquired across all sites, and reductions in target lesion sum of diameter were seen across the range of TIL total cell doses.

All patients experienced at least one adverse event of any grade; all but two experienced grade 3 or 4 adverse events. Two patients died, one as a result of intra-abdominal hemorrhage considered possibly related to TIL therapy, and one from acute respiratory failure deemed not related to TILs.

The most common grade 3 or 4 adverse events were thrombocytopenia, anemia, febrile neutropenia, neutropenia, hypophosphatemia, and lymphopenia.

“The adverse event profile was manageable and was consistent with the underlying and the known profiles of the nonmyeloblative depletion regimen and IL-2,” Dr. Chesney said.

The decreasing frequency of adverse events over time reflects the potential benefit of the one-time infusion, and no new safety risks have been identified during more than 2 years of follow-up, he added.
 

Remaining questions, next steps

Dr. Greenberg commented that the one of the limitations of the study is that the investigators did not characterize the TIL product.

“Studies have predicted that there’s a particular type of cell, a stemlike T cell, that’s responsible for mediating the efficacy,” he commented. He referred to research from Steven Rosenberg, MD, PhD, and colleagues at the National Cancer Institute, where TILs were first used in 2002.

Dr. Greenberg also raised the question of whether high-dose IL-2 was required post infusion, given that the patients were lymphodepleted before receiving lifileucel.

Future steps for TIL therapy, he said, should include identification of biomarkers for success or failure; strategies to enhance generation and expansion of tumor-reactive T cells; postinfusion strategies, such as using vaccines and/or checkpoint inhibitors to increase therapeutic activity; genetic modifications to enhance the function of TILs in the tumor microenvironment; and research into other tumor types that may be effectively treated with TILs.

The study was supported by Iovance Biotherapeutics. Dr. Chesney has received research funding from Iovance and other companies and has consulted for Amgen and Replimune. Dr. Greenberg has served on scientific advisory boards, has received grant/research support, and owns stock in several companies that do not include Iovance.

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

NEW ORLEANS – In just over one-third of patients with metastatic melanoma who had experienced disease progression while receiving multiple prior lines of therapy, including immunotherapy and targeted agents, objective clinical responses occurred with a customized cell therapy based on T cells extracted directly from tumor tissue.

The product, called lifileucel, is custom made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from tumor lesions. This approach differs from other cell-based therapies, such as chimeric antigen receptor (CAR) T cell therapy, which utilizes T cells collected from the patient’s blood.

The new results come from a phase 2 trial conducted in 66 patients with previously treated unresectable or metastatic melanoma who received a single dose of the product. The objective response rate was 36.4%.

“Lifileucel has demonstrated efficacy and durability of response for patients with metastatic melanoma and represents a viable therapeutic option warranting further investigation,” commented Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville (Ky.).

He presented the new data at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.

Customized cell therapy with TILs has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.

However, “generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells,” commented Philip Greenberg, MD, professor and head of the program in immunology in the Clinical Research Division of the Fred Hutchinson Cancer Center, Seattle, who was the invited discussant.

The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise. The patient-specific products are then disseminated to multiple centers, he said. The study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes.

“Toxicity was, however, significant, although it was generally manageable, and it did occur early, generally within the first 2 weeks,” he noted.
 

Patient-derived product

Lifileucel is a tailor-made immunotherapy product created from melanoma tumor tissues resected from lesions in skin, lymph nodes, liver, lung, peritoneum, musculoskeletal system, breast, or other visceral organs. The cells are shipped to a central manufacturing facility, whre the TILs are isolated, cultured, expanded, and reinvigorated. The cells are then harvested and cryopreserved. The process takes about 22 days. The cryopreserved product is then shipped back to the treating facility.

Prior to receiving the expanded and rejuvenated TILs, patients undergo myeloablative conditioning with cyclophosphamide followed by fludarabine. The TILs are then delivered in a single infusion, followed by administration of up to six doses of interleukin-2 (IL-2).
 

Details from clinical trial

At the meeting, Dr. Chesney reported details on the 66 patients in the trial. They had metastatic melanoma that was progressing on treatment. The mean number of prior lines of therapy was 3.3. All of the patients had received prior anti–programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1) agents; 53 had received a cytotoxic T lymphocyte protein 4 (CTLA-4) inhibitor; and 15 had received a BRAF/MEK inhibitor.

These patients had a mean of six baseline target and nontarget lesions, and 28 patients had liver and/or brain metastases.

Just over a third of patients (24 of 66, 36.4%) had an objective response; three patients had a complete response; and 21 had a partial response. In addition, 29 patients had stable disease, and nine experienced disease progression. Four patients had not undergone the first assessment at the time of data cutoff.

After a median follow-up of 28.1 months, the median duration of response was not reached. It ranged from 2.2 to > 35.2 months.

Since the data cutoff in April 2020, reduction of tumor burden has occurred in 50 of 62 evaluable patients. Reductions in the target lesion sum of diameters has occurred in 11 patients. In one patient, a partial response converted to a complete response 24 months after infusion, Dr. Chesney noted.

The mean number of TILs infused was 27.3 billion (27.3 x 109). Appropriate amounts of TILs were manufactured from tumor samples acquired across all sites, and reductions in target lesion sum of diameter were seen across the range of TIL total cell doses.

All patients experienced at least one adverse event of any grade; all but two experienced grade 3 or 4 adverse events. Two patients died, one as a result of intra-abdominal hemorrhage considered possibly related to TIL therapy, and one from acute respiratory failure deemed not related to TILs.

The most common grade 3 or 4 adverse events were thrombocytopenia, anemia, febrile neutropenia, neutropenia, hypophosphatemia, and lymphopenia.

“The adverse event profile was manageable and was consistent with the underlying and the known profiles of the nonmyeloblative depletion regimen and IL-2,” Dr. Chesney said.

The decreasing frequency of adverse events over time reflects the potential benefit of the one-time infusion, and no new safety risks have been identified during more than 2 years of follow-up, he added.
 

Remaining questions, next steps

Dr. Greenberg commented that the one of the limitations of the study is that the investigators did not characterize the TIL product.

“Studies have predicted that there’s a particular type of cell, a stemlike T cell, that’s responsible for mediating the efficacy,” he commented. He referred to research from Steven Rosenberg, MD, PhD, and colleagues at the National Cancer Institute, where TILs were first used in 2002.

Dr. Greenberg also raised the question of whether high-dose IL-2 was required post infusion, given that the patients were lymphodepleted before receiving lifileucel.

Future steps for TIL therapy, he said, should include identification of biomarkers for success or failure; strategies to enhance generation and expansion of tumor-reactive T cells; postinfusion strategies, such as using vaccines and/or checkpoint inhibitors to increase therapeutic activity; genetic modifications to enhance the function of TILs in the tumor microenvironment; and research into other tumor types that may be effectively treated with TILs.

The study was supported by Iovance Biotherapeutics. Dr. Chesney has received research funding from Iovance and other companies and has consulted for Amgen and Replimune. Dr. Greenberg has served on scientific advisory boards, has received grant/research support, and owns stock in several companies that do not include Iovance.

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

NEW ORLEANS – In just over one-third of patients with metastatic melanoma who had experienced disease progression while receiving multiple prior lines of therapy, including immunotherapy and targeted agents, objective clinical responses occurred with a customized cell therapy based on T cells extracted directly from tumor tissue.

The product, called lifileucel, is custom made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from tumor lesions. This approach differs from other cell-based therapies, such as chimeric antigen receptor (CAR) T cell therapy, which utilizes T cells collected from the patient’s blood.

The new results come from a phase 2 trial conducted in 66 patients with previously treated unresectable or metastatic melanoma who received a single dose of the product. The objective response rate was 36.4%.

“Lifileucel has demonstrated efficacy and durability of response for patients with metastatic melanoma and represents a viable therapeutic option warranting further investigation,” commented Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville (Ky.).

He presented the new data at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.

Customized cell therapy with TILs has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.

However, “generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells,” commented Philip Greenberg, MD, professor and head of the program in immunology in the Clinical Research Division of the Fred Hutchinson Cancer Center, Seattle, who was the invited discussant.

The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise. The patient-specific products are then disseminated to multiple centers, he said. The study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes.

“Toxicity was, however, significant, although it was generally manageable, and it did occur early, generally within the first 2 weeks,” he noted.
 

Patient-derived product

Lifileucel is a tailor-made immunotherapy product created from melanoma tumor tissues resected from lesions in skin, lymph nodes, liver, lung, peritoneum, musculoskeletal system, breast, or other visceral organs. The cells are shipped to a central manufacturing facility, whre the TILs are isolated, cultured, expanded, and reinvigorated. The cells are then harvested and cryopreserved. The process takes about 22 days. The cryopreserved product is then shipped back to the treating facility.

Prior to receiving the expanded and rejuvenated TILs, patients undergo myeloablative conditioning with cyclophosphamide followed by fludarabine. The TILs are then delivered in a single infusion, followed by administration of up to six doses of interleukin-2 (IL-2).
 

Details from clinical trial

At the meeting, Dr. Chesney reported details on the 66 patients in the trial. They had metastatic melanoma that was progressing on treatment. The mean number of prior lines of therapy was 3.3. All of the patients had received prior anti–programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1) agents; 53 had received a cytotoxic T lymphocyte protein 4 (CTLA-4) inhibitor; and 15 had received a BRAF/MEK inhibitor.

These patients had a mean of six baseline target and nontarget lesions, and 28 patients had liver and/or brain metastases.

Just over a third of patients (24 of 66, 36.4%) had an objective response; three patients had a complete response; and 21 had a partial response. In addition, 29 patients had stable disease, and nine experienced disease progression. Four patients had not undergone the first assessment at the time of data cutoff.

After a median follow-up of 28.1 months, the median duration of response was not reached. It ranged from 2.2 to > 35.2 months.

Since the data cutoff in April 2020, reduction of tumor burden has occurred in 50 of 62 evaluable patients. Reductions in the target lesion sum of diameters has occurred in 11 patients. In one patient, a partial response converted to a complete response 24 months after infusion, Dr. Chesney noted.

The mean number of TILs infused was 27.3 billion (27.3 x 109). Appropriate amounts of TILs were manufactured from tumor samples acquired across all sites, and reductions in target lesion sum of diameter were seen across the range of TIL total cell doses.

All patients experienced at least one adverse event of any grade; all but two experienced grade 3 or 4 adverse events. Two patients died, one as a result of intra-abdominal hemorrhage considered possibly related to TIL therapy, and one from acute respiratory failure deemed not related to TILs.

The most common grade 3 or 4 adverse events were thrombocytopenia, anemia, febrile neutropenia, neutropenia, hypophosphatemia, and lymphopenia.

“The adverse event profile was manageable and was consistent with the underlying and the known profiles of the nonmyeloblative depletion regimen and IL-2,” Dr. Chesney said.

The decreasing frequency of adverse events over time reflects the potential benefit of the one-time infusion, and no new safety risks have been identified during more than 2 years of follow-up, he added.
 

Remaining questions, next steps

Dr. Greenberg commented that the one of the limitations of the study is that the investigators did not characterize the TIL product.

“Studies have predicted that there’s a particular type of cell, a stemlike T cell, that’s responsible for mediating the efficacy,” he commented. He referred to research from Steven Rosenberg, MD, PhD, and colleagues at the National Cancer Institute, where TILs were first used in 2002.

Dr. Greenberg also raised the question of whether high-dose IL-2 was required post infusion, given that the patients were lymphodepleted before receiving lifileucel.

Future steps for TIL therapy, he said, should include identification of biomarkers for success or failure; strategies to enhance generation and expansion of tumor-reactive T cells; postinfusion strategies, such as using vaccines and/or checkpoint inhibitors to increase therapeutic activity; genetic modifications to enhance the function of TILs in the tumor microenvironment; and research into other tumor types that may be effectively treated with TILs.

The study was supported by Iovance Biotherapeutics. Dr. Chesney has received research funding from Iovance and other companies and has consulted for Amgen and Replimune. Dr. Greenberg has served on scientific advisory boards, has received grant/research support, and owns stock in several companies that do not include Iovance.

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

NEW ORLEANS – One third of patients with non–small cell lung cancers (NSCLC) bearing the KRASG12C mutation were alive 2 years after starting therapy with the first-in-class KRAS inhibitor sotorasib (Lumakras, Amgen).

The finding comes from an analysis of long-term follow-up data from the CodeBreaK100 trial, which showed a 2-year overall survival (OS) rate of 32.5% in pretreated patients with KRASG12C-mutant disease.

That rate compares favorably with historical data on NSCLC therapies, said Grace K. Dy, MD, from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

“We expect about half of that [survival rate] in patients who are treated with docetaxel,” she said in a plenary session at the annual meeting of the American Association for Cancer Research.

Sotorasib was approved by the Food and Drug Administration in May 2021 as the first drug for patients with NSCLC and KRAS mutations and was described as a “historic milestone.” 

In this most recent analysis, which combined data from patients enrolled in phases 1 and 2 of the trial, the “objective response rate of 41% of patients was achieved with sotorasib, with a durable [disease] control rate of 84% and a median duration of response of 12.3 months, with no new safety signals emerging,” she said.

Nearly one-fourth of patients saw long-term benefit, as defined by progression-free survival of at least 12 months, and this long-term benefit was seen across variant allele frequencies of KRASG12C, programmed death–ligand 1 (PD-L1) tumor proportion score, and other comutations, she noted.

“KRASG12C inhibitors represent a major advance in the treatment of KRAS-mutant lung cancers and other types as well,” said invited discussant Mark M. Awad, MD, PhD, director of clinical research at the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Center, Boston.

He cautioned, however, that “the therapeutic efficacy of these G12C inhibitors is currently limited by several things, including patient factors, intrinsic biology, and the emergence of complex resistance mechanisms.”

New approaches will be needed, he said, “to delay and overcome drug resistance to hopefully keep kicking cancer’s KRAS.”

At a media briefing where Dr. Dy presented the data prior to the oral abstract session, moderator Timothy A. Yap, MBBS, PhD, from the University of Texas MD Anderson Cancer Center, Houston, commented that the development of drug resistance is common in oncology.

“That is exactly why we’re now actively working on multiple different combinatorial approaches in the clinic. There have been pretty compelling data published from Mirati [Therapeutics] and from other companies, from Amgen, that really show the resistance mechanisms that actually come about upon monotherapy with KRASG12C inhibitors, including CDK4/6, including P13K-Akt pathways,” he said.

“The solution there really is, No. 1, we need to identify proactively the resistance mechanisms involved and driving each cancer’s resistance, and No. 2, then apply the combinatorial agent, to bring in a combination that’s a rational approach to match a patient’s molecular profile upon resistance,” he said.
 

Tarnished triumph

As previously reported, sotorasib was hailed as “a triumph of drug discovery” when early results of the trial were reported at the European Society of Medical Oncology annual meeting in 2020.

Sotorasib is a small-molecule, specific, and irreversible inhibitor of KRAS that interacts with a “pocket” on the gene’s surface that is present only in an inactive conformation of KRAS. The drug inhibits oncogenic signaling and tumorigenesis by preventing cycling of the oncogene into its active form.

But as Dr. Awad reported at the 2021 AACR annual meeting, the efficacy of sotorasib and other KRAS inhibitors in development has been threatened by the development of resistance caused by a wide range of genomic and histologic mechanisms.

Dr. Awad reported that among 30 patients with NSCLC or colorectal cancer bearing the KRASG12C mutation who had disease progression while being treated with the investigational inhibitor adagrasib in clinical trials, investigators found multiple on-target KRAS alterations and off-target bypass mechanisms of acquired resistance to the drug.

“Diverse mechanisms confer resistance to the KRASG12C inhibitors, including secondary KRAS mutations, MAP [mitogen-activated protein] kinase pathway alterations, acquired genomic rearrangements, and histologic transformation,” he said.
 

Long follow-up

The long-term data reported at the 2022 meeting by Dr. Dy and colleagues included data on 48 patients enrolled in phase 1 of the trial, which had a primary endpoint of safety and tolerability, and 126 patients enrolled in phase 2, with a primary endpoint of objective response rate by blinded independent review.

The trial was conducted in centers in the United States, Europe, Australia, Japan, and South Korea.

Nearly all patients were pretreated: 92.5% of patients had received prior platinum-based chemotherapy and 90.2% had received anti–PD-1/PD-L1 immunotherapy.

Patients received oral sotorasib 960 mg once daily and were followed with radiographic scans every 6 weeks for the first year and once every 12 weeks thereafter.

Of the 174 patients enrolled, two were not evaluable for response at 2 years because of a lack of measurable lesions at baseline.

At a median follow-up of 24.9 months, 5 patients (2.9%) had a complete response and 65 (37.8%) had a partial response, for an objective response rate of 40.7%. An additional 74 patients (43%) had stable disease, for a disease control rate of 83.7%. Of the remaining patients, 23 (13.4%) had disease progression, and 5 were either not evaluable or had missing scan data.

Median progression-free survival was 6.3 months. Median time to response was 6 weeks, and median duration of response was 12.3 months. Half of patients who had a response retained that response for at least 12 months.

Median OS was 12.5 months. The 1-year and 2-year OS rates were 50.8% and 32.5%, respectively.

Grade 3 or 4 treatment-related adverse events occurred in 21% of patients, and one patient had new-onset grade 3 hemolytic anemia 1 year after starting therapy. There were no treatment-related deaths and no treatment-related adverse events leading to discontinuation after the first year.

In exploratory analyses, the benefit of the drug was seen across tumors with varying levels of PD-L1 expression and the oncogenic STK11 comutation, and across KRASG12C variant allele frequency.

The investigators also reported that baseline circulating tumor DNA levels correlated with tumor burden, and that patients who had long-term benefits had lower baseline ctDNA. This finding is consistent with the documented role of ctDNA as a marker for poor prognosis regardless of therapy.

Dr. Dy reported receiving consulting fees from AstraZeneca, Eli Lilly, Mirati Therapeutics, and Takeda in the past 2 years. Dr. Yap disclosed receiving consulting fees from multiple companies. Dr. Awad disclosed consulting for multiple companies.

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

NEW ORLEANS – One third of patients with non–small cell lung cancers (NSCLC) bearing the KRASG12C mutation were alive 2 years after starting therapy with the first-in-class KRAS inhibitor sotorasib (Lumakras, Amgen).

The finding comes from an analysis of long-term follow-up data from the CodeBreaK100 trial, which showed a 2-year overall survival (OS) rate of 32.5% in pretreated patients with KRASG12C-mutant disease.

That rate compares favorably with historical data on NSCLC therapies, said Grace K. Dy, MD, from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

“We expect about half of that [survival rate] in patients who are treated with docetaxel,” she said in a plenary session at the annual meeting of the American Association for Cancer Research.

Sotorasib was approved by the Food and Drug Administration in May 2021 as the first drug for patients with NSCLC and KRAS mutations and was described as a “historic milestone.” 

In this most recent analysis, which combined data from patients enrolled in phases 1 and 2 of the trial, the “objective response rate of 41% of patients was achieved with sotorasib, with a durable [disease] control rate of 84% and a median duration of response of 12.3 months, with no new safety signals emerging,” she said.

Nearly one-fourth of patients saw long-term benefit, as defined by progression-free survival of at least 12 months, and this long-term benefit was seen across variant allele frequencies of KRASG12C, programmed death–ligand 1 (PD-L1) tumor proportion score, and other comutations, she noted.

“KRASG12C inhibitors represent a major advance in the treatment of KRAS-mutant lung cancers and other types as well,” said invited discussant Mark M. Awad, MD, PhD, director of clinical research at the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Center, Boston.

He cautioned, however, that “the therapeutic efficacy of these G12C inhibitors is currently limited by several things, including patient factors, intrinsic biology, and the emergence of complex resistance mechanisms.”

New approaches will be needed, he said, “to delay and overcome drug resistance to hopefully keep kicking cancer’s KRAS.”

At a media briefing where Dr. Dy presented the data prior to the oral abstract session, moderator Timothy A. Yap, MBBS, PhD, from the University of Texas MD Anderson Cancer Center, Houston, commented that the development of drug resistance is common in oncology.

“That is exactly why we’re now actively working on multiple different combinatorial approaches in the clinic. There have been pretty compelling data published from Mirati [Therapeutics] and from other companies, from Amgen, that really show the resistance mechanisms that actually come about upon monotherapy with KRASG12C inhibitors, including CDK4/6, including P13K-Akt pathways,” he said.

“The solution there really is, No. 1, we need to identify proactively the resistance mechanisms involved and driving each cancer’s resistance, and No. 2, then apply the combinatorial agent, to bring in a combination that’s a rational approach to match a patient’s molecular profile upon resistance,” he said.
 

Tarnished triumph

As previously reported, sotorasib was hailed as “a triumph of drug discovery” when early results of the trial were reported at the European Society of Medical Oncology annual meeting in 2020.

Sotorasib is a small-molecule, specific, and irreversible inhibitor of KRAS that interacts with a “pocket” on the gene’s surface that is present only in an inactive conformation of KRAS. The drug inhibits oncogenic signaling and tumorigenesis by preventing cycling of the oncogene into its active form.

But as Dr. Awad reported at the 2021 AACR annual meeting, the efficacy of sotorasib and other KRAS inhibitors in development has been threatened by the development of resistance caused by a wide range of genomic and histologic mechanisms.

Dr. Awad reported that among 30 patients with NSCLC or colorectal cancer bearing the KRASG12C mutation who had disease progression while being treated with the investigational inhibitor adagrasib in clinical trials, investigators found multiple on-target KRAS alterations and off-target bypass mechanisms of acquired resistance to the drug.

“Diverse mechanisms confer resistance to the KRASG12C inhibitors, including secondary KRAS mutations, MAP [mitogen-activated protein] kinase pathway alterations, acquired genomic rearrangements, and histologic transformation,” he said.
 

Long follow-up

The long-term data reported at the 2022 meeting by Dr. Dy and colleagues included data on 48 patients enrolled in phase 1 of the trial, which had a primary endpoint of safety and tolerability, and 126 patients enrolled in phase 2, with a primary endpoint of objective response rate by blinded independent review.

The trial was conducted in centers in the United States, Europe, Australia, Japan, and South Korea.

Nearly all patients were pretreated: 92.5% of patients had received prior platinum-based chemotherapy and 90.2% had received anti–PD-1/PD-L1 immunotherapy.

Patients received oral sotorasib 960 mg once daily and were followed with radiographic scans every 6 weeks for the first year and once every 12 weeks thereafter.

Of the 174 patients enrolled, two were not evaluable for response at 2 years because of a lack of measurable lesions at baseline.

At a median follow-up of 24.9 months, 5 patients (2.9%) had a complete response and 65 (37.8%) had a partial response, for an objective response rate of 40.7%. An additional 74 patients (43%) had stable disease, for a disease control rate of 83.7%. Of the remaining patients, 23 (13.4%) had disease progression, and 5 were either not evaluable or had missing scan data.

Median progression-free survival was 6.3 months. Median time to response was 6 weeks, and median duration of response was 12.3 months. Half of patients who had a response retained that response for at least 12 months.

Median OS was 12.5 months. The 1-year and 2-year OS rates were 50.8% and 32.5%, respectively.

Grade 3 or 4 treatment-related adverse events occurred in 21% of patients, and one patient had new-onset grade 3 hemolytic anemia 1 year after starting therapy. There were no treatment-related deaths and no treatment-related adverse events leading to discontinuation after the first year.

In exploratory analyses, the benefit of the drug was seen across tumors with varying levels of PD-L1 expression and the oncogenic STK11 comutation, and across KRASG12C variant allele frequency.

The investigators also reported that baseline circulating tumor DNA levels correlated with tumor burden, and that patients who had long-term benefits had lower baseline ctDNA. This finding is consistent with the documented role of ctDNA as a marker for poor prognosis regardless of therapy.

Dr. Dy reported receiving consulting fees from AstraZeneca, Eli Lilly, Mirati Therapeutics, and Takeda in the past 2 years. Dr. Yap disclosed receiving consulting fees from multiple companies. Dr. Awad disclosed consulting for multiple companies.

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

NEW ORLEANS – One third of patients with non–small cell lung cancers (NSCLC) bearing the KRASG12C mutation were alive 2 years after starting therapy with the first-in-class KRAS inhibitor sotorasib (Lumakras, Amgen).

The finding comes from an analysis of long-term follow-up data from the CodeBreaK100 trial, which showed a 2-year overall survival (OS) rate of 32.5% in pretreated patients with KRASG12C-mutant disease.

That rate compares favorably with historical data on NSCLC therapies, said Grace K. Dy, MD, from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

“We expect about half of that [survival rate] in patients who are treated with docetaxel,” she said in a plenary session at the annual meeting of the American Association for Cancer Research.

Sotorasib was approved by the Food and Drug Administration in May 2021 as the first drug for patients with NSCLC and KRAS mutations and was described as a “historic milestone.” 

In this most recent analysis, which combined data from patients enrolled in phases 1 and 2 of the trial, the “objective response rate of 41% of patients was achieved with sotorasib, with a durable [disease] control rate of 84% and a median duration of response of 12.3 months, with no new safety signals emerging,” she said.

Nearly one-fourth of patients saw long-term benefit, as defined by progression-free survival of at least 12 months, and this long-term benefit was seen across variant allele frequencies of KRASG12C, programmed death–ligand 1 (PD-L1) tumor proportion score, and other comutations, she noted.

“KRASG12C inhibitors represent a major advance in the treatment of KRAS-mutant lung cancers and other types as well,” said invited discussant Mark M. Awad, MD, PhD, director of clinical research at the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Center, Boston.

He cautioned, however, that “the therapeutic efficacy of these G12C inhibitors is currently limited by several things, including patient factors, intrinsic biology, and the emergence of complex resistance mechanisms.”

New approaches will be needed, he said, “to delay and overcome drug resistance to hopefully keep kicking cancer’s KRAS.”

At a media briefing where Dr. Dy presented the data prior to the oral abstract session, moderator Timothy A. Yap, MBBS, PhD, from the University of Texas MD Anderson Cancer Center, Houston, commented that the development of drug resistance is common in oncology.

“That is exactly why we’re now actively working on multiple different combinatorial approaches in the clinic. There have been pretty compelling data published from Mirati [Therapeutics] and from other companies, from Amgen, that really show the resistance mechanisms that actually come about upon monotherapy with KRASG12C inhibitors, including CDK4/6, including P13K-Akt pathways,” he said.

“The solution there really is, No. 1, we need to identify proactively the resistance mechanisms involved and driving each cancer’s resistance, and No. 2, then apply the combinatorial agent, to bring in a combination that’s a rational approach to match a patient’s molecular profile upon resistance,” he said.
 

Tarnished triumph

As previously reported, sotorasib was hailed as “a triumph of drug discovery” when early results of the trial were reported at the European Society of Medical Oncology annual meeting in 2020.

Sotorasib is a small-molecule, specific, and irreversible inhibitor of KRAS that interacts with a “pocket” on the gene’s surface that is present only in an inactive conformation of KRAS. The drug inhibits oncogenic signaling and tumorigenesis by preventing cycling of the oncogene into its active form.

But as Dr. Awad reported at the 2021 AACR annual meeting, the efficacy of sotorasib and other KRAS inhibitors in development has been threatened by the development of resistance caused by a wide range of genomic and histologic mechanisms.

Dr. Awad reported that among 30 patients with NSCLC or colorectal cancer bearing the KRASG12C mutation who had disease progression while being treated with the investigational inhibitor adagrasib in clinical trials, investigators found multiple on-target KRAS alterations and off-target bypass mechanisms of acquired resistance to the drug.

“Diverse mechanisms confer resistance to the KRASG12C inhibitors, including secondary KRAS mutations, MAP [mitogen-activated protein] kinase pathway alterations, acquired genomic rearrangements, and histologic transformation,” he said.
 

Long follow-up

The long-term data reported at the 2022 meeting by Dr. Dy and colleagues included data on 48 patients enrolled in phase 1 of the trial, which had a primary endpoint of safety and tolerability, and 126 patients enrolled in phase 2, with a primary endpoint of objective response rate by blinded independent review.

The trial was conducted in centers in the United States, Europe, Australia, Japan, and South Korea.

Nearly all patients were pretreated: 92.5% of patients had received prior platinum-based chemotherapy and 90.2% had received anti–PD-1/PD-L1 immunotherapy.

Patients received oral sotorasib 960 mg once daily and were followed with radiographic scans every 6 weeks for the first year and once every 12 weeks thereafter.

Of the 174 patients enrolled, two were not evaluable for response at 2 years because of a lack of measurable lesions at baseline.

At a median follow-up of 24.9 months, 5 patients (2.9%) had a complete response and 65 (37.8%) had a partial response, for an objective response rate of 40.7%. An additional 74 patients (43%) had stable disease, for a disease control rate of 83.7%. Of the remaining patients, 23 (13.4%) had disease progression, and 5 were either not evaluable or had missing scan data.

Median progression-free survival was 6.3 months. Median time to response was 6 weeks, and median duration of response was 12.3 months. Half of patients who had a response retained that response for at least 12 months.

Median OS was 12.5 months. The 1-year and 2-year OS rates were 50.8% and 32.5%, respectively.

Grade 3 or 4 treatment-related adverse events occurred in 21% of patients, and one patient had new-onset grade 3 hemolytic anemia 1 year after starting therapy. There were no treatment-related deaths and no treatment-related adverse events leading to discontinuation after the first year.

In exploratory analyses, the benefit of the drug was seen across tumors with varying levels of PD-L1 expression and the oncogenic STK11 comutation, and across KRASG12C variant allele frequency.

The investigators also reported that baseline circulating tumor DNA levels correlated with tumor burden, and that patients who had long-term benefits had lower baseline ctDNA. This finding is consistent with the documented role of ctDNA as a marker for poor prognosis regardless of therapy.

Dr. Dy reported receiving consulting fees from AstraZeneca, Eli Lilly, Mirati Therapeutics, and Takeda in the past 2 years. Dr. Yap disclosed receiving consulting fees from multiple companies. Dr. Awad disclosed consulting for multiple companies.

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