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FDA approves belimumab for children with lupus nephritis
The Food and Drug Administration has approved belimumab (Benlysta) for treating active lupus nephritis (LN) in children aged 5-17 years. The drug can now be used to treat adult and pediatric patients with systemic lupus erythematosus (SLE) and LN. The decision expands therapeutic options for the estimated 1.5 million Americans currently living with lupus.
“This approval marks a significant step forward in providing treatment options to these children at risk of incurring kidney damage early on in life,” Stevan W. Gibson, president and CEO of the Lupus Foundation of America, said in a press release issued by the manufacturer, GlaxoSmithKline. LN is a condition that sometimes develops in people with lupus. In LN, the autoimmune cells produced by the disease attack the kidney. Roughly 40% of people with SLE experience LN.
Damage to the kidneys causes the body to have difficulty processing waste and toxins. This can create a host of problems, including end-stage kidney disease, which may be treated only with dialysis or kidney transplant. These situations significantly increase mortality among people with lupus, especially children.
Prior to the approval, the only treatment pathway for children with active LN included immunosuppressants and corticosteroids. While they may be effective, use of these classes of drugs may come with many side effects, including susceptibility to other diseases and infections. Belimumab, by contrast, is a B-lymphocyte stimulator protein inhibitor. It inhibits the survival of B cells, which are thought to play a role in the disease’s pathophysiology.
Belimumab was first approved to treat patients with SLE in 2011. It was approved for children with SLE 8 years later. The drug’s indications were expanded to include adults with LN in 2020.
Organizations within the lupus research community have communicated their support of the FDA’s decision. “Our community has much to celebrate with the approval of the first and much-needed treatment for children with lupus nephritis,” Lupus Research Alliance President and CEO Kenneth M. Farber said in a release from the organization.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved belimumab (Benlysta) for treating active lupus nephritis (LN) in children aged 5-17 years. The drug can now be used to treat adult and pediatric patients with systemic lupus erythematosus (SLE) and LN. The decision expands therapeutic options for the estimated 1.5 million Americans currently living with lupus.
“This approval marks a significant step forward in providing treatment options to these children at risk of incurring kidney damage early on in life,” Stevan W. Gibson, president and CEO of the Lupus Foundation of America, said in a press release issued by the manufacturer, GlaxoSmithKline. LN is a condition that sometimes develops in people with lupus. In LN, the autoimmune cells produced by the disease attack the kidney. Roughly 40% of people with SLE experience LN.
Damage to the kidneys causes the body to have difficulty processing waste and toxins. This can create a host of problems, including end-stage kidney disease, which may be treated only with dialysis or kidney transplant. These situations significantly increase mortality among people with lupus, especially children.
Prior to the approval, the only treatment pathway for children with active LN included immunosuppressants and corticosteroids. While they may be effective, use of these classes of drugs may come with many side effects, including susceptibility to other diseases and infections. Belimumab, by contrast, is a B-lymphocyte stimulator protein inhibitor. It inhibits the survival of B cells, which are thought to play a role in the disease’s pathophysiology.
Belimumab was first approved to treat patients with SLE in 2011. It was approved for children with SLE 8 years later. The drug’s indications were expanded to include adults with LN in 2020.
Organizations within the lupus research community have communicated their support of the FDA’s decision. “Our community has much to celebrate with the approval of the first and much-needed treatment for children with lupus nephritis,” Lupus Research Alliance President and CEO Kenneth M. Farber said in a release from the organization.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved belimumab (Benlysta) for treating active lupus nephritis (LN) in children aged 5-17 years. The drug can now be used to treat adult and pediatric patients with systemic lupus erythematosus (SLE) and LN. The decision expands therapeutic options for the estimated 1.5 million Americans currently living with lupus.
“This approval marks a significant step forward in providing treatment options to these children at risk of incurring kidney damage early on in life,” Stevan W. Gibson, president and CEO of the Lupus Foundation of America, said in a press release issued by the manufacturer, GlaxoSmithKline. LN is a condition that sometimes develops in people with lupus. In LN, the autoimmune cells produced by the disease attack the kidney. Roughly 40% of people with SLE experience LN.
Damage to the kidneys causes the body to have difficulty processing waste and toxins. This can create a host of problems, including end-stage kidney disease, which may be treated only with dialysis or kidney transplant. These situations significantly increase mortality among people with lupus, especially children.
Prior to the approval, the only treatment pathway for children with active LN included immunosuppressants and corticosteroids. While they may be effective, use of these classes of drugs may come with many side effects, including susceptibility to other diseases and infections. Belimumab, by contrast, is a B-lymphocyte stimulator protein inhibitor. It inhibits the survival of B cells, which are thought to play a role in the disease’s pathophysiology.
Belimumab was first approved to treat patients with SLE in 2011. It was approved for children with SLE 8 years later. The drug’s indications were expanded to include adults with LN in 2020.
Organizations within the lupus research community have communicated their support of the FDA’s decision. “Our community has much to celebrate with the approval of the first and much-needed treatment for children with lupus nephritis,” Lupus Research Alliance President and CEO Kenneth M. Farber said in a release from the organization.
A version of this article first appeared on Medscape.com.
To gauge monkeypox spread, researchers eye cases in women
As cases of monkeypox continue to mount in the United States and abroad, infectious disease experts are closely monitoring one group of people in particular: women.
So far, the overwhelming majority of cases of the viral disease have been reported in men who have sex with men. But in recent days, officials have learned of a handful of cases in women – possibly indicating that the outbreak may be widening.
Researchers are keeping close tabs on the proportion of cases in women to “assess whether the outbreak is moving away” from networks of men who have sex with men, where most of the initial cases have been identified, according to a briefing from the UK Health Security Agency (UKHSA).
“There is insufficient evidence to support a change in the transmission dynamics,” the agency said. “However, over the last few weeks the proportion of female cases has been increasing, so this trend needs to be monitored closely.”
A global collaboration of researchers and clinicians recently described 528 cases of monkeypox in 16 countries – but none were in women.
Since data collection for that study ended in June, the research group has confirmed cases in women, said study coauthor John P. Thornhill, MD, PhD, consultant physician in sexual health and HIV and clinical senior lecturer at Barts Health NHS Trust and Queen Mary University of London.
“Cases in women have certainly been reported but are currently far less common,” Dr. Thornhill told this news organization.
Although infections in women have been outliers during the current outbreak, they can be severe when they do occur. Several women in England have been hospitalized with severe symptoms.
A similar pattern has been seen in New York City, where just one woman is among the 639 total cases, according to a July 21 report from the city’s health agency.
Researchers have recently published guidance on monkeypox for ob.gyns., maternal-fetal medicine subspecialists, and people who are pregnant or breastfeeding in anticipation of the possibility of more cases in women.
The Centers for Disease Control and Prevention advises that “pregnant, recently pregnant, and breastfeeding people should be prioritized for medical treatment” of monkeypox if needed.
One monkeypox vaccine, Jynneos, can be offered to people who are pregnant or breastfeeding and are otherwise eligible for vaccination on the basis of confirmed or likely contact with cases, ideally within 4 days of exposure. Some people at high risk for exposure, such as laboratory workers, may receive the vaccine preemptively.
Another vaccine, ACAM2000, is contraindicated in people who are pregnant or breastfeeding, according to the CDC.
Transmission dynamics
Investigators have not yet identified substantial spread of monkeypox beyond men who have sex with men, although transmission among household contacts, including women and children, has been reported.
Most initial infections during the current outbreak occurred during sexual activity. But monkeypox can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC. It also may spread from mother to child in utero.
Infected pets have been known to spread the disease as well. A multistate monkeypox outbreak in the United States in 2003 was linked to pet prairie dogs, including in childcare and school settings. That year, 55% of the 71 cases occurred in female patients.
More testing, higher positivity rates in men
Since May, more men than women in the United Kingdom have undergone testing for monkeypox, with 3,467 tests in men versus 447 tests in women. Among those tested, the positivity rate has been far higher in men than in women, 54% versus 2.2%, respectively.
As of July 20, about 0.65% of U.K. cases with known gender were in women. Two weeks prior, about 0.4% were in women.
In all, 13 monkeypox cases in England have been in women, and four had severe manifestations that required hospitalization, according to the UKHSA.
Globally, more than 16,000 monkeypox cases have been reported, according to the World Health Organization. The agency said that it plans to rename the disease to reduce stigma.
Monkeypox and pregnancy
Ob.gyns. are often on the “front line in terms of identifying people with infectious diseases,” said Denise J. Jamieson, MD, MPH, Emory University, Atlanta. Dr. Jamieson coauthored “A Primer on Monkeypox Virus for Obstetrician-Gynecologists,” published in Obstetrics & Gynecology.
“Obstetricians need to be aware of what infectious diseases are circulating and be aware of what is going on in the community,” she said.
With monkeypox, “it is anybody’s guess as to how widespread this is going to be,” Dr. Jamieson said.
“The initial monkeypox cases in the current outbreak have been predominately but not exclusively among men who have sex with men; enhanced transmission in this group may be facilitated by sexual activity and spread through complex sexual networks,” Dr. Thornhill said. “As the outbreak continues, we will likely see more monkeypox infections” outside that group.
“Those working in sexual health should have a high index of suspicion in all individuals presenting with genital and oral ulcers and those with proctitis,” he added.
During previous monkeypox outbreaks, the chain of household transmissions has been short, typically two or three people, said Chloe M. Orkin, MD, professor of HIV medicine at Queen Mary University of London. Dr. Orkin directs the Sexual Health and HIV All East Research (SHARE) Collaborative, which has worked to compile the international case series.
Though monkeypox has mainly been transmitted among men who have sex with men, not all identify as gay and some may also have female and nonbinary partners, Dr. Orkin said.
“Clinicians should bear this in mind when examining any person,” she said.
A version of this article first appeared on Medscape.com.
As cases of monkeypox continue to mount in the United States and abroad, infectious disease experts are closely monitoring one group of people in particular: women.
So far, the overwhelming majority of cases of the viral disease have been reported in men who have sex with men. But in recent days, officials have learned of a handful of cases in women – possibly indicating that the outbreak may be widening.
Researchers are keeping close tabs on the proportion of cases in women to “assess whether the outbreak is moving away” from networks of men who have sex with men, where most of the initial cases have been identified, according to a briefing from the UK Health Security Agency (UKHSA).
“There is insufficient evidence to support a change in the transmission dynamics,” the agency said. “However, over the last few weeks the proportion of female cases has been increasing, so this trend needs to be monitored closely.”
A global collaboration of researchers and clinicians recently described 528 cases of monkeypox in 16 countries – but none were in women.
Since data collection for that study ended in June, the research group has confirmed cases in women, said study coauthor John P. Thornhill, MD, PhD, consultant physician in sexual health and HIV and clinical senior lecturer at Barts Health NHS Trust and Queen Mary University of London.
“Cases in women have certainly been reported but are currently far less common,” Dr. Thornhill told this news organization.
Although infections in women have been outliers during the current outbreak, they can be severe when they do occur. Several women in England have been hospitalized with severe symptoms.
A similar pattern has been seen in New York City, where just one woman is among the 639 total cases, according to a July 21 report from the city’s health agency.
Researchers have recently published guidance on monkeypox for ob.gyns., maternal-fetal medicine subspecialists, and people who are pregnant or breastfeeding in anticipation of the possibility of more cases in women.
The Centers for Disease Control and Prevention advises that “pregnant, recently pregnant, and breastfeeding people should be prioritized for medical treatment” of monkeypox if needed.
One monkeypox vaccine, Jynneos, can be offered to people who are pregnant or breastfeeding and are otherwise eligible for vaccination on the basis of confirmed or likely contact with cases, ideally within 4 days of exposure. Some people at high risk for exposure, such as laboratory workers, may receive the vaccine preemptively.
Another vaccine, ACAM2000, is contraindicated in people who are pregnant or breastfeeding, according to the CDC.
Transmission dynamics
Investigators have not yet identified substantial spread of monkeypox beyond men who have sex with men, although transmission among household contacts, including women and children, has been reported.
Most initial infections during the current outbreak occurred during sexual activity. But monkeypox can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC. It also may spread from mother to child in utero.
Infected pets have been known to spread the disease as well. A multistate monkeypox outbreak in the United States in 2003 was linked to pet prairie dogs, including in childcare and school settings. That year, 55% of the 71 cases occurred in female patients.
More testing, higher positivity rates in men
Since May, more men than women in the United Kingdom have undergone testing for monkeypox, with 3,467 tests in men versus 447 tests in women. Among those tested, the positivity rate has been far higher in men than in women, 54% versus 2.2%, respectively.
As of July 20, about 0.65% of U.K. cases with known gender were in women. Two weeks prior, about 0.4% were in women.
In all, 13 monkeypox cases in England have been in women, and four had severe manifestations that required hospitalization, according to the UKHSA.
Globally, more than 16,000 monkeypox cases have been reported, according to the World Health Organization. The agency said that it plans to rename the disease to reduce stigma.
Monkeypox and pregnancy
Ob.gyns. are often on the “front line in terms of identifying people with infectious diseases,” said Denise J. Jamieson, MD, MPH, Emory University, Atlanta. Dr. Jamieson coauthored “A Primer on Monkeypox Virus for Obstetrician-Gynecologists,” published in Obstetrics & Gynecology.
“Obstetricians need to be aware of what infectious diseases are circulating and be aware of what is going on in the community,” she said.
With monkeypox, “it is anybody’s guess as to how widespread this is going to be,” Dr. Jamieson said.
“The initial monkeypox cases in the current outbreak have been predominately but not exclusively among men who have sex with men; enhanced transmission in this group may be facilitated by sexual activity and spread through complex sexual networks,” Dr. Thornhill said. “As the outbreak continues, we will likely see more monkeypox infections” outside that group.
“Those working in sexual health should have a high index of suspicion in all individuals presenting with genital and oral ulcers and those with proctitis,” he added.
During previous monkeypox outbreaks, the chain of household transmissions has been short, typically two or three people, said Chloe M. Orkin, MD, professor of HIV medicine at Queen Mary University of London. Dr. Orkin directs the Sexual Health and HIV All East Research (SHARE) Collaborative, which has worked to compile the international case series.
Though monkeypox has mainly been transmitted among men who have sex with men, not all identify as gay and some may also have female and nonbinary partners, Dr. Orkin said.
“Clinicians should bear this in mind when examining any person,” she said.
A version of this article first appeared on Medscape.com.
As cases of monkeypox continue to mount in the United States and abroad, infectious disease experts are closely monitoring one group of people in particular: women.
So far, the overwhelming majority of cases of the viral disease have been reported in men who have sex with men. But in recent days, officials have learned of a handful of cases in women – possibly indicating that the outbreak may be widening.
Researchers are keeping close tabs on the proportion of cases in women to “assess whether the outbreak is moving away” from networks of men who have sex with men, where most of the initial cases have been identified, according to a briefing from the UK Health Security Agency (UKHSA).
“There is insufficient evidence to support a change in the transmission dynamics,” the agency said. “However, over the last few weeks the proportion of female cases has been increasing, so this trend needs to be monitored closely.”
A global collaboration of researchers and clinicians recently described 528 cases of monkeypox in 16 countries – but none were in women.
Since data collection for that study ended in June, the research group has confirmed cases in women, said study coauthor John P. Thornhill, MD, PhD, consultant physician in sexual health and HIV and clinical senior lecturer at Barts Health NHS Trust and Queen Mary University of London.
“Cases in women have certainly been reported but are currently far less common,” Dr. Thornhill told this news organization.
Although infections in women have been outliers during the current outbreak, they can be severe when they do occur. Several women in England have been hospitalized with severe symptoms.
A similar pattern has been seen in New York City, where just one woman is among the 639 total cases, according to a July 21 report from the city’s health agency.
Researchers have recently published guidance on monkeypox for ob.gyns., maternal-fetal medicine subspecialists, and people who are pregnant or breastfeeding in anticipation of the possibility of more cases in women.
The Centers for Disease Control and Prevention advises that “pregnant, recently pregnant, and breastfeeding people should be prioritized for medical treatment” of monkeypox if needed.
One monkeypox vaccine, Jynneos, can be offered to people who are pregnant or breastfeeding and are otherwise eligible for vaccination on the basis of confirmed or likely contact with cases, ideally within 4 days of exposure. Some people at high risk for exposure, such as laboratory workers, may receive the vaccine preemptively.
Another vaccine, ACAM2000, is contraindicated in people who are pregnant or breastfeeding, according to the CDC.
Transmission dynamics
Investigators have not yet identified substantial spread of monkeypox beyond men who have sex with men, although transmission among household contacts, including women and children, has been reported.
Most initial infections during the current outbreak occurred during sexual activity. But monkeypox can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC. It also may spread from mother to child in utero.
Infected pets have been known to spread the disease as well. A multistate monkeypox outbreak in the United States in 2003 was linked to pet prairie dogs, including in childcare and school settings. That year, 55% of the 71 cases occurred in female patients.
More testing, higher positivity rates in men
Since May, more men than women in the United Kingdom have undergone testing for monkeypox, with 3,467 tests in men versus 447 tests in women. Among those tested, the positivity rate has been far higher in men than in women, 54% versus 2.2%, respectively.
As of July 20, about 0.65% of U.K. cases with known gender were in women. Two weeks prior, about 0.4% were in women.
In all, 13 monkeypox cases in England have been in women, and four had severe manifestations that required hospitalization, according to the UKHSA.
Globally, more than 16,000 monkeypox cases have been reported, according to the World Health Organization. The agency said that it plans to rename the disease to reduce stigma.
Monkeypox and pregnancy
Ob.gyns. are often on the “front line in terms of identifying people with infectious diseases,” said Denise J. Jamieson, MD, MPH, Emory University, Atlanta. Dr. Jamieson coauthored “A Primer on Monkeypox Virus for Obstetrician-Gynecologists,” published in Obstetrics & Gynecology.
“Obstetricians need to be aware of what infectious diseases are circulating and be aware of what is going on in the community,” she said.
With monkeypox, “it is anybody’s guess as to how widespread this is going to be,” Dr. Jamieson said.
“The initial monkeypox cases in the current outbreak have been predominately but not exclusively among men who have sex with men; enhanced transmission in this group may be facilitated by sexual activity and spread through complex sexual networks,” Dr. Thornhill said. “As the outbreak continues, we will likely see more monkeypox infections” outside that group.
“Those working in sexual health should have a high index of suspicion in all individuals presenting with genital and oral ulcers and those with proctitis,” he added.
During previous monkeypox outbreaks, the chain of household transmissions has been short, typically two or three people, said Chloe M. Orkin, MD, professor of HIV medicine at Queen Mary University of London. Dr. Orkin directs the Sexual Health and HIV All East Research (SHARE) Collaborative, which has worked to compile the international case series.
Though monkeypox has mainly been transmitted among men who have sex with men, not all identify as gay and some may also have female and nonbinary partners, Dr. Orkin said.
“Clinicians should bear this in mind when examining any person,” she said.
A version of this article first appeared on Medscape.com.
Life and death decisions: What keeps oncologists up at night
It was 2 a.m. And Rebecca Shatsky, MD, could not sleep.
The breast oncologist was thinking about a patient of hers with metastatic cancer.
The patient’s disease had been asymptomatic for some time. Then without warning, her cancer suddenly exploded. Her bone marrow was failing, and her liver was not far behind.
Dr. Shatsky had a treatment plan ready to go but still, she felt uneasy.
“I had to be honest with her that I didn’t know if this plan would work,” says Dr. Shatsky, a medical oncologist at University of California, San Diego (UCSD).
That night, after visiting the patient in the hospital, Dr. Shatsky lay awake going over her next move, making sure it was the right one and hoping it would help keep the disease at bay.
“It’s so much pressure when someone is depending on you to make life or death decisions,” Dr. Shatsky said.
And in the quiet hours of night, these concerns grow louder.
Dr. Shatsky is not alone.
“There’s no off button,” says Aaron Goodman, MD, a hematologist at UCSD Health who goes by “Papa Heme” on Twitter. “I’m always thinking about my patients. Constantly.”
The public rarely gets a glimpse of these private moments. On occasion, oncologists will share a personal story, but more often, insights come from broad research on the ethical, emotional, and psychological toll of practicing medicine.
Many oncologists carry this baggage home with them because they have no other option.
“There is simply no time to process the weight of the day when I’ve got seven more patients who need my full attention before lunch,” Mark Lewis, MD, director, department of gastrointestinal oncology, Intermountain Healthcare, Salt Lake City, Utah. “That is why my processing happens outside of the office, when my brain can be quiet.”
What am I missing?
Dr. Goodman recognizes the gravity of each decision he makes. He pores over every detail of a patient’s scans, lab results, history, and symptoms.
But no matter how many times he checks and rechecks, one question nags at him: What am I missing?
For Dr. Goodman, this exhaustive level of attention is worth it.
“When errors are made, it’s someone’s life,” Dr. Goodman said. “Nothing would have prepared me for this responsibility. Until it lies on you, it’s impossible to understand how much trust patients put into us.”
That trust becomes most apparent for Dr. Goodman when facing a decision about how to treat a patient with acute myeloid leukemia who’s in remission.
Give more chemotherapy to root out the leukemia cells still lurking in the body, and the patient faces a high risk of the cancer returning. Pick stem cell transplant, and the chance of being cured goes up significantly, but the patient could also die within 100 days of the transplant.
“All together, the data show I’m helping patients with a transplant, but for the individual, I could be causing harm. Someone could be living less because of a decision I made,” Dr. Goodman said.
For patients with advanced cancer, oncologists may need to think several moves ahead. Mapping out a patient’s treatment options can feel like a game of chess. Dr. Shatsky is always trying to anticipate how the tumor will behave, what is driving it, and how lifestyle factors may influence a patient’s response in the present and the future.
“It is a mind game,” she says. “Like in chess, I try to outsmart my opponent. But with advanced cancer, there are not necessarily clear-cut guidelines or one way to manage the disease, and I have to do the best I can with drugs I have.”
That’s the art of oncology: Balancing the many knowns and unknowns of a person’s cancer alongside the toxicities of treatment and a patient’s hopes and goals.
Throughout the year, Don Dizon, MD, will see a number of patients with advanced disease. In these instances, the question he often wrestles with is if the patient can’t be cured, whether more treatment will just cause greater harm.
Dr. Dizon recently faced this dilemma with an older patient with metastatic disease who had not done well with an initial treatment regimen. After outlining the risks for more chemotherapy, he explained one option would be to forgo it and simply treat her symptoms.
“It’s an impossible choice,” says Dr. Dizon, director of women’s cancers at Lifespan Cancer Institute and director of medical oncology at Rhode Island Hospital, Providence.
Chemotherapy can provide symptom relief, but it can also be toxic – and patients may be so frail, they can die from more therapy.
“I told my patient, if in your heart, you want to try more therapy, that’s okay. But it’s also okay if you don’t,” Dr. Dizon recalled.
Her response: “You’re supposed to give me the answer.”
However, for patients approaching the end of life, there often is no right answer.
“It’s part of the discomfort you live with as a patient and oncologist, and when I leave the clinic, that’s one thing that follows me home,” Dr. Dizon said. “At the end of the day, I need to look in the mirror and know I did the best I could.”
The difficult conversation
Every Sunday, Dr. Lewis feels the weight of the week ahead. He and his wife, a pediatrician, call it the “Sunday scaries.”
It’s when Dr. Lewis begins thinking about the delicate conversations to come, rehearsing how he’s going to share the news that a person has advanced cancer or that a cancer, once in remission, has returned.
“Before the pandemic, I had 36 people come to a visit where I delivered some very heavy news and it became a Greek chorus of sobbing,” he recalls.
For every oncologist, delivering bad news is an integral part of the job. But after spending months, sometimes years, with a patient and the family, Dr. Lewis knows how to take the temperature of the room – who will likely prefer a more blunt style and who might need a gentler touch.
“The longer you know a patient and family, the better you can gauge the best approach,” Dr. Lewis said. “And for some, you know it’ll be complete devastation no matter what.”
When Jennifer Lycette, MD, prepares for a difficult conversation, she’ll run down all the possible ways it could go. Sometimes her brain will get stuck in a loop, cycling through the different trajectories on repeat.
“For years, I didn’t know how to cope with that,” said Dr. Lycette, medical director at Providence Oncology and Hematology Care Clinic in Seaside, Ore. “I wasn’t taught the tools to cope with that in my medical training. It took midcareer professional coaching that I sought out on my own to learn to remind myself that no matter what the person says, I have the experience and skill set to handle what comes next and to simply be present in the moment with the patient.”
The question that now sits with Dr. Lycette hours after a visit is what she could have done better. She knows from experience how important it is to choose her words carefully.
Early in her career, Dr. Lycette had a patient with stage IV cancer who wanted to know more about the death process. Because most people ask about pain, she assured him that he likely wouldn’t experience too much pain with his type of cancer.
“It will probably be like falling asleep,” said Dr. Lycette, hoping she was offering comfort. “When I saw him next, he told me he hadn’t slept.”
He was afraid that if he did, he wouldn’t wake up.
In that moment, Dr. Lycette realized the power that her words carry and the importance of trying to understand the inner lives of her patients.
Life outside the clinic
Sometimes an oncologist’s late-night ruminations have little to do with cancer itself.
Manali Patel, MD, finds herself worrying if her patients will have enough to eat and whether she will be able to help.
“I was up at 3 a.m. one morning, thinking about how we’re going to fund a project for patients from low-income households who we discovered were experiencing severe food insecurity – what grants we need, what foundations we can work with,” said Dr. Patel, a medical oncologist at Stanford Hospital and Clinics and the VA Palo Alto Health Care System in California.
The past few years of the pandemic have added a new layer of worry for Dr. Patel.
“I don’t want my patients to die from a preventable virus when they’ve already been through so much suffering,” Dr. Patel said.
This thought feeds worries about how her actions outside the clinic could unintentionally harm her patients. Should she go to a big medical conference? A family gathering? The grocery store?
“There are some places you can’t avoid, but these decisions have caused a lot of strife for me,” she said. “The health and safety of our patients – that’s in our wheelhouse – but so many of the policies are outside of our control.”
The inevitable losses and the wins
For patients with metastatic disease, eventually the treatment options will run out.
Dr. Shatsky likes to be up front with patients about that reality: “There will come a day when I will tell you there’s nothing more I can do, and you need to trust that I’m being honest with you and that’s the truth.”
For Dr. Goodman, the devastation that bad news brings patients and families is glaring. He knows there will be no more normalcy in their lives.
“I see a lot of suffering, but I know the suffering happens regardless of whether I see it or not,” Dr. Goodman said.
That’s why holding on to the victories can be so important. Dr. Goodman recalled a young patient who came to him with a 20-cm tumor and is now cured. “Had I not met that individual and done what I had done, he’d be dead, but now he’s going to live his life,” Dr. Goodman said. “But I don’t wake up at 2 a.m. thinking about that.”
Dr. Shatsky gets a lot of joy from the wins – the patients who do really well, the times when she can help a friend or colleagues – and those moments go a long way to outweigh the hurt, worry, and workload.
When dealing with so much gray, “the wins are important, knowing you can make a difference is important,” Dr. Dizon said.
And there’s a delicate balance.
“I think patients want an oncologist who cares and is genuinely invested in their outcomes but not someone who is so sad all the time,” Dr. Lewis said. “When I lose a patient, I still grieve each loss, but I can’t mourn every patient’s death like it’s a family member. Otherwise, I’d break.”
What would you do if you had terminal cancer?
Dr. Dizon recalled how a friend handled the news. She went home and made dinner, he said.
Ultimately, she lived for many years. She saw her kids get married, met her first grandchild, and had time to prepare, something not everyone gets the chance to do.
That’s why it’s important to “do what you normally do as long as you can,” Dr. Dizon said. “Live your life.”
A version of this article first appeared on Medscape.com.
It was 2 a.m. And Rebecca Shatsky, MD, could not sleep.
The breast oncologist was thinking about a patient of hers with metastatic cancer.
The patient’s disease had been asymptomatic for some time. Then without warning, her cancer suddenly exploded. Her bone marrow was failing, and her liver was not far behind.
Dr. Shatsky had a treatment plan ready to go but still, she felt uneasy.
“I had to be honest with her that I didn’t know if this plan would work,” says Dr. Shatsky, a medical oncologist at University of California, San Diego (UCSD).
That night, after visiting the patient in the hospital, Dr. Shatsky lay awake going over her next move, making sure it was the right one and hoping it would help keep the disease at bay.
“It’s so much pressure when someone is depending on you to make life or death decisions,” Dr. Shatsky said.
And in the quiet hours of night, these concerns grow louder.
Dr. Shatsky is not alone.
“There’s no off button,” says Aaron Goodman, MD, a hematologist at UCSD Health who goes by “Papa Heme” on Twitter. “I’m always thinking about my patients. Constantly.”
The public rarely gets a glimpse of these private moments. On occasion, oncologists will share a personal story, but more often, insights come from broad research on the ethical, emotional, and psychological toll of practicing medicine.
Many oncologists carry this baggage home with them because they have no other option.
“There is simply no time to process the weight of the day when I’ve got seven more patients who need my full attention before lunch,” Mark Lewis, MD, director, department of gastrointestinal oncology, Intermountain Healthcare, Salt Lake City, Utah. “That is why my processing happens outside of the office, when my brain can be quiet.”
What am I missing?
Dr. Goodman recognizes the gravity of each decision he makes. He pores over every detail of a patient’s scans, lab results, history, and symptoms.
But no matter how many times he checks and rechecks, one question nags at him: What am I missing?
For Dr. Goodman, this exhaustive level of attention is worth it.
“When errors are made, it’s someone’s life,” Dr. Goodman said. “Nothing would have prepared me for this responsibility. Until it lies on you, it’s impossible to understand how much trust patients put into us.”
That trust becomes most apparent for Dr. Goodman when facing a decision about how to treat a patient with acute myeloid leukemia who’s in remission.
Give more chemotherapy to root out the leukemia cells still lurking in the body, and the patient faces a high risk of the cancer returning. Pick stem cell transplant, and the chance of being cured goes up significantly, but the patient could also die within 100 days of the transplant.
“All together, the data show I’m helping patients with a transplant, but for the individual, I could be causing harm. Someone could be living less because of a decision I made,” Dr. Goodman said.
For patients with advanced cancer, oncologists may need to think several moves ahead. Mapping out a patient’s treatment options can feel like a game of chess. Dr. Shatsky is always trying to anticipate how the tumor will behave, what is driving it, and how lifestyle factors may influence a patient’s response in the present and the future.
“It is a mind game,” she says. “Like in chess, I try to outsmart my opponent. But with advanced cancer, there are not necessarily clear-cut guidelines or one way to manage the disease, and I have to do the best I can with drugs I have.”
That’s the art of oncology: Balancing the many knowns and unknowns of a person’s cancer alongside the toxicities of treatment and a patient’s hopes and goals.
Throughout the year, Don Dizon, MD, will see a number of patients with advanced disease. In these instances, the question he often wrestles with is if the patient can’t be cured, whether more treatment will just cause greater harm.
Dr. Dizon recently faced this dilemma with an older patient with metastatic disease who had not done well with an initial treatment regimen. After outlining the risks for more chemotherapy, he explained one option would be to forgo it and simply treat her symptoms.
“It’s an impossible choice,” says Dr. Dizon, director of women’s cancers at Lifespan Cancer Institute and director of medical oncology at Rhode Island Hospital, Providence.
Chemotherapy can provide symptom relief, but it can also be toxic – and patients may be so frail, they can die from more therapy.
“I told my patient, if in your heart, you want to try more therapy, that’s okay. But it’s also okay if you don’t,” Dr. Dizon recalled.
Her response: “You’re supposed to give me the answer.”
However, for patients approaching the end of life, there often is no right answer.
“It’s part of the discomfort you live with as a patient and oncologist, and when I leave the clinic, that’s one thing that follows me home,” Dr. Dizon said. “At the end of the day, I need to look in the mirror and know I did the best I could.”
The difficult conversation
Every Sunday, Dr. Lewis feels the weight of the week ahead. He and his wife, a pediatrician, call it the “Sunday scaries.”
It’s when Dr. Lewis begins thinking about the delicate conversations to come, rehearsing how he’s going to share the news that a person has advanced cancer or that a cancer, once in remission, has returned.
“Before the pandemic, I had 36 people come to a visit where I delivered some very heavy news and it became a Greek chorus of sobbing,” he recalls.
For every oncologist, delivering bad news is an integral part of the job. But after spending months, sometimes years, with a patient and the family, Dr. Lewis knows how to take the temperature of the room – who will likely prefer a more blunt style and who might need a gentler touch.
“The longer you know a patient and family, the better you can gauge the best approach,” Dr. Lewis said. “And for some, you know it’ll be complete devastation no matter what.”
When Jennifer Lycette, MD, prepares for a difficult conversation, she’ll run down all the possible ways it could go. Sometimes her brain will get stuck in a loop, cycling through the different trajectories on repeat.
“For years, I didn’t know how to cope with that,” said Dr. Lycette, medical director at Providence Oncology and Hematology Care Clinic in Seaside, Ore. “I wasn’t taught the tools to cope with that in my medical training. It took midcareer professional coaching that I sought out on my own to learn to remind myself that no matter what the person says, I have the experience and skill set to handle what comes next and to simply be present in the moment with the patient.”
The question that now sits with Dr. Lycette hours after a visit is what she could have done better. She knows from experience how important it is to choose her words carefully.
Early in her career, Dr. Lycette had a patient with stage IV cancer who wanted to know more about the death process. Because most people ask about pain, she assured him that he likely wouldn’t experience too much pain with his type of cancer.
“It will probably be like falling asleep,” said Dr. Lycette, hoping she was offering comfort. “When I saw him next, he told me he hadn’t slept.”
He was afraid that if he did, he wouldn’t wake up.
In that moment, Dr. Lycette realized the power that her words carry and the importance of trying to understand the inner lives of her patients.
Life outside the clinic
Sometimes an oncologist’s late-night ruminations have little to do with cancer itself.
Manali Patel, MD, finds herself worrying if her patients will have enough to eat and whether she will be able to help.
“I was up at 3 a.m. one morning, thinking about how we’re going to fund a project for patients from low-income households who we discovered were experiencing severe food insecurity – what grants we need, what foundations we can work with,” said Dr. Patel, a medical oncologist at Stanford Hospital and Clinics and the VA Palo Alto Health Care System in California.
The past few years of the pandemic have added a new layer of worry for Dr. Patel.
“I don’t want my patients to die from a preventable virus when they’ve already been through so much suffering,” Dr. Patel said.
This thought feeds worries about how her actions outside the clinic could unintentionally harm her patients. Should she go to a big medical conference? A family gathering? The grocery store?
“There are some places you can’t avoid, but these decisions have caused a lot of strife for me,” she said. “The health and safety of our patients – that’s in our wheelhouse – but so many of the policies are outside of our control.”
The inevitable losses and the wins
For patients with metastatic disease, eventually the treatment options will run out.
Dr. Shatsky likes to be up front with patients about that reality: “There will come a day when I will tell you there’s nothing more I can do, and you need to trust that I’m being honest with you and that’s the truth.”
For Dr. Goodman, the devastation that bad news brings patients and families is glaring. He knows there will be no more normalcy in their lives.
“I see a lot of suffering, but I know the suffering happens regardless of whether I see it or not,” Dr. Goodman said.
That’s why holding on to the victories can be so important. Dr. Goodman recalled a young patient who came to him with a 20-cm tumor and is now cured. “Had I not met that individual and done what I had done, he’d be dead, but now he’s going to live his life,” Dr. Goodman said. “But I don’t wake up at 2 a.m. thinking about that.”
Dr. Shatsky gets a lot of joy from the wins – the patients who do really well, the times when she can help a friend or colleagues – and those moments go a long way to outweigh the hurt, worry, and workload.
When dealing with so much gray, “the wins are important, knowing you can make a difference is important,” Dr. Dizon said.
And there’s a delicate balance.
“I think patients want an oncologist who cares and is genuinely invested in their outcomes but not someone who is so sad all the time,” Dr. Lewis said. “When I lose a patient, I still grieve each loss, but I can’t mourn every patient’s death like it’s a family member. Otherwise, I’d break.”
What would you do if you had terminal cancer?
Dr. Dizon recalled how a friend handled the news. She went home and made dinner, he said.
Ultimately, she lived for many years. She saw her kids get married, met her first grandchild, and had time to prepare, something not everyone gets the chance to do.
That’s why it’s important to “do what you normally do as long as you can,” Dr. Dizon said. “Live your life.”
A version of this article first appeared on Medscape.com.
It was 2 a.m. And Rebecca Shatsky, MD, could not sleep.
The breast oncologist was thinking about a patient of hers with metastatic cancer.
The patient’s disease had been asymptomatic for some time. Then without warning, her cancer suddenly exploded. Her bone marrow was failing, and her liver was not far behind.
Dr. Shatsky had a treatment plan ready to go but still, she felt uneasy.
“I had to be honest with her that I didn’t know if this plan would work,” says Dr. Shatsky, a medical oncologist at University of California, San Diego (UCSD).
That night, after visiting the patient in the hospital, Dr. Shatsky lay awake going over her next move, making sure it was the right one and hoping it would help keep the disease at bay.
“It’s so much pressure when someone is depending on you to make life or death decisions,” Dr. Shatsky said.
And in the quiet hours of night, these concerns grow louder.
Dr. Shatsky is not alone.
“There’s no off button,” says Aaron Goodman, MD, a hematologist at UCSD Health who goes by “Papa Heme” on Twitter. “I’m always thinking about my patients. Constantly.”
The public rarely gets a glimpse of these private moments. On occasion, oncologists will share a personal story, but more often, insights come from broad research on the ethical, emotional, and psychological toll of practicing medicine.
Many oncologists carry this baggage home with them because they have no other option.
“There is simply no time to process the weight of the day when I’ve got seven more patients who need my full attention before lunch,” Mark Lewis, MD, director, department of gastrointestinal oncology, Intermountain Healthcare, Salt Lake City, Utah. “That is why my processing happens outside of the office, when my brain can be quiet.”
What am I missing?
Dr. Goodman recognizes the gravity of each decision he makes. He pores over every detail of a patient’s scans, lab results, history, and symptoms.
But no matter how many times he checks and rechecks, one question nags at him: What am I missing?
For Dr. Goodman, this exhaustive level of attention is worth it.
“When errors are made, it’s someone’s life,” Dr. Goodman said. “Nothing would have prepared me for this responsibility. Until it lies on you, it’s impossible to understand how much trust patients put into us.”
That trust becomes most apparent for Dr. Goodman when facing a decision about how to treat a patient with acute myeloid leukemia who’s in remission.
Give more chemotherapy to root out the leukemia cells still lurking in the body, and the patient faces a high risk of the cancer returning. Pick stem cell transplant, and the chance of being cured goes up significantly, but the patient could also die within 100 days of the transplant.
“All together, the data show I’m helping patients with a transplant, but for the individual, I could be causing harm. Someone could be living less because of a decision I made,” Dr. Goodman said.
For patients with advanced cancer, oncologists may need to think several moves ahead. Mapping out a patient’s treatment options can feel like a game of chess. Dr. Shatsky is always trying to anticipate how the tumor will behave, what is driving it, and how lifestyle factors may influence a patient’s response in the present and the future.
“It is a mind game,” she says. “Like in chess, I try to outsmart my opponent. But with advanced cancer, there are not necessarily clear-cut guidelines or one way to manage the disease, and I have to do the best I can with drugs I have.”
That’s the art of oncology: Balancing the many knowns and unknowns of a person’s cancer alongside the toxicities of treatment and a patient’s hopes and goals.
Throughout the year, Don Dizon, MD, will see a number of patients with advanced disease. In these instances, the question he often wrestles with is if the patient can’t be cured, whether more treatment will just cause greater harm.
Dr. Dizon recently faced this dilemma with an older patient with metastatic disease who had not done well with an initial treatment regimen. After outlining the risks for more chemotherapy, he explained one option would be to forgo it and simply treat her symptoms.
“It’s an impossible choice,” says Dr. Dizon, director of women’s cancers at Lifespan Cancer Institute and director of medical oncology at Rhode Island Hospital, Providence.
Chemotherapy can provide symptom relief, but it can also be toxic – and patients may be so frail, they can die from more therapy.
“I told my patient, if in your heart, you want to try more therapy, that’s okay. But it’s also okay if you don’t,” Dr. Dizon recalled.
Her response: “You’re supposed to give me the answer.”
However, for patients approaching the end of life, there often is no right answer.
“It’s part of the discomfort you live with as a patient and oncologist, and when I leave the clinic, that’s one thing that follows me home,” Dr. Dizon said. “At the end of the day, I need to look in the mirror and know I did the best I could.”
The difficult conversation
Every Sunday, Dr. Lewis feels the weight of the week ahead. He and his wife, a pediatrician, call it the “Sunday scaries.”
It’s when Dr. Lewis begins thinking about the delicate conversations to come, rehearsing how he’s going to share the news that a person has advanced cancer or that a cancer, once in remission, has returned.
“Before the pandemic, I had 36 people come to a visit where I delivered some very heavy news and it became a Greek chorus of sobbing,” he recalls.
For every oncologist, delivering bad news is an integral part of the job. But after spending months, sometimes years, with a patient and the family, Dr. Lewis knows how to take the temperature of the room – who will likely prefer a more blunt style and who might need a gentler touch.
“The longer you know a patient and family, the better you can gauge the best approach,” Dr. Lewis said. “And for some, you know it’ll be complete devastation no matter what.”
When Jennifer Lycette, MD, prepares for a difficult conversation, she’ll run down all the possible ways it could go. Sometimes her brain will get stuck in a loop, cycling through the different trajectories on repeat.
“For years, I didn’t know how to cope with that,” said Dr. Lycette, medical director at Providence Oncology and Hematology Care Clinic in Seaside, Ore. “I wasn’t taught the tools to cope with that in my medical training. It took midcareer professional coaching that I sought out on my own to learn to remind myself that no matter what the person says, I have the experience and skill set to handle what comes next and to simply be present in the moment with the patient.”
The question that now sits with Dr. Lycette hours after a visit is what she could have done better. She knows from experience how important it is to choose her words carefully.
Early in her career, Dr. Lycette had a patient with stage IV cancer who wanted to know more about the death process. Because most people ask about pain, she assured him that he likely wouldn’t experience too much pain with his type of cancer.
“It will probably be like falling asleep,” said Dr. Lycette, hoping she was offering comfort. “When I saw him next, he told me he hadn’t slept.”
He was afraid that if he did, he wouldn’t wake up.
In that moment, Dr. Lycette realized the power that her words carry and the importance of trying to understand the inner lives of her patients.
Life outside the clinic
Sometimes an oncologist’s late-night ruminations have little to do with cancer itself.
Manali Patel, MD, finds herself worrying if her patients will have enough to eat and whether she will be able to help.
“I was up at 3 a.m. one morning, thinking about how we’re going to fund a project for patients from low-income households who we discovered were experiencing severe food insecurity – what grants we need, what foundations we can work with,” said Dr. Patel, a medical oncologist at Stanford Hospital and Clinics and the VA Palo Alto Health Care System in California.
The past few years of the pandemic have added a new layer of worry for Dr. Patel.
“I don’t want my patients to die from a preventable virus when they’ve already been through so much suffering,” Dr. Patel said.
This thought feeds worries about how her actions outside the clinic could unintentionally harm her patients. Should she go to a big medical conference? A family gathering? The grocery store?
“There are some places you can’t avoid, but these decisions have caused a lot of strife for me,” she said. “The health and safety of our patients – that’s in our wheelhouse – but so many of the policies are outside of our control.”
The inevitable losses and the wins
For patients with metastatic disease, eventually the treatment options will run out.
Dr. Shatsky likes to be up front with patients about that reality: “There will come a day when I will tell you there’s nothing more I can do, and you need to trust that I’m being honest with you and that’s the truth.”
For Dr. Goodman, the devastation that bad news brings patients and families is glaring. He knows there will be no more normalcy in their lives.
“I see a lot of suffering, but I know the suffering happens regardless of whether I see it or not,” Dr. Goodman said.
That’s why holding on to the victories can be so important. Dr. Goodman recalled a young patient who came to him with a 20-cm tumor and is now cured. “Had I not met that individual and done what I had done, he’d be dead, but now he’s going to live his life,” Dr. Goodman said. “But I don’t wake up at 2 a.m. thinking about that.”
Dr. Shatsky gets a lot of joy from the wins – the patients who do really well, the times when she can help a friend or colleagues – and those moments go a long way to outweigh the hurt, worry, and workload.
When dealing with so much gray, “the wins are important, knowing you can make a difference is important,” Dr. Dizon said.
And there’s a delicate balance.
“I think patients want an oncologist who cares and is genuinely invested in their outcomes but not someone who is so sad all the time,” Dr. Lewis said. “When I lose a patient, I still grieve each loss, but I can’t mourn every patient’s death like it’s a family member. Otherwise, I’d break.”
What would you do if you had terminal cancer?
Dr. Dizon recalled how a friend handled the news. She went home and made dinner, he said.
Ultimately, she lived for many years. She saw her kids get married, met her first grandchild, and had time to prepare, something not everyone gets the chance to do.
That’s why it’s important to “do what you normally do as long as you can,” Dr. Dizon said. “Live your life.”
A version of this article first appeared on Medscape.com.
TNF inhibitor use for RA shows beneficial effect in pregnancy
Women with well-controlled rheumatoid arthritis who used a tumor necrosis factor (TNF) inhibitor during pregnancy gave birth to infants with higher birth weight than did other patients, without an increased risk of adverse outcomes, according to findings from a Dutch prospective cohort study published online in Annals of the Rheumatic Diseases.
The study involved 188 patients drawn from the ongoing Preconceptional Counseling in Active RA (PreCARA) study, which followed patients with inflammatory rheumatic diseases before and during pregnancy. Women enrolled in PreCARA were closely monitored and treated with a therapeutic approach that aimed to achieve minimal disease activity, which included the use of TNF inhibitors.
Much research on TNF inhibitors during pregnancy has been limited to the first trimester and focused primarily on congenital malformations. In addition, most previous studies evaluating TNF inhibitors during pregnancy involved patients with different underlying diseases, making it difficult to interpret the results.
Hieronymus T. W. Smeele, MD, and colleagues at Erasmus University Medical Center, Rotterdam, the Netherlands, evaluated participants every 3 months before pregnancy; then again in the first, second, and third trimesters; and at 6, 12, and 26 weeks post partum. At these visits, in addition to undergoing an examination of their joints, patients completed questionnaires and gave blood samples. Disease activity was determined using the Disease Activity Score in 28 joints. Twin births and diagnoses other than RA were excluded.
Bigger babies
The study found that use of TNF inhibitors during pregnancy (n = 92 women) did not increase the risk of birth defects or emergency cesarean sections. While RA is typically associated with small-for-gestational-age (SGA) birth weights, TNF inhibitors were associated with a significant increase in birth weight and fewer infants born SGA, even when the comparison was adjusted for confounders, such as disease activity. At the same time, TNF inhibitors were not associated with high birth weight or with infants who were large for gestational age (LGA).
The results showed that the effects were greatest when TNF inhibitors were used in the third trimester. However, teasing out the effects based on trimester is difficult because participants who used TNF inhibitors during the third trimester were likely to use them in the first and second trimester as well. The study’s authors pointed out that these results need to be replicated.
“The immune system is not only important in the pathogenesis of RA,” the study’s authors wrote, “but also for ensuring and maintaining a normal pregnancy.” They pointed out that many adverse outcomes of pregnancy that are thought to arise from inadequate development of the placenta, such as intrauterine growth restriction, SGA, and hypertensive disorders of pregnancy, can involve an increase in proinflammatory cytokines, such as TNF. “It is tempting to speculate that treatment with [TNF inhibitors] during pregnancy promotes placentation and thereby fetal growth and birth weight by changing the balance between proinflammatory and anti-inflammatory cytokines and by increasing the number and function of [regulatory T cells].” They also hypothesize that treatment with TNF inhibitors induces epigenetic changes in the fetus, which positively influence fetal growth.
Welcomed data
This is a well-done, interesting study that will add to the still-slim body of research on pregnancy in rheumatic diseases, Kevin Byram, MD, assistant professor of medicine in the division of rheumatology and immunology and associate director of the rheumatology training program at Vanderbilt University, Nashville, Tenn., told this news organization.
“Historically, pregnant women have been excluded from clinical trials, not just in rheumatoid arthritis, but in other rheumatic diseases, so we don’t have a lot of great data,” he said, adding that the more interesting part of the study was that it showed there was no increased risk of adverse outcomes. “I’m not sure what to make of the increased birth weight. It will be interesting to see if the hypothesis that there might be a role for this molecule in preventing low birth weight goes anywhere.”
The work was supported by the Dutch Arthritis Foundation. PreCARA is an investigator-initiated study that was financially supported by UCB. The authors declared no competing interests.
A version of this article first appeared on Medscape.com.
Women with well-controlled rheumatoid arthritis who used a tumor necrosis factor (TNF) inhibitor during pregnancy gave birth to infants with higher birth weight than did other patients, without an increased risk of adverse outcomes, according to findings from a Dutch prospective cohort study published online in Annals of the Rheumatic Diseases.
The study involved 188 patients drawn from the ongoing Preconceptional Counseling in Active RA (PreCARA) study, which followed patients with inflammatory rheumatic diseases before and during pregnancy. Women enrolled in PreCARA were closely monitored and treated with a therapeutic approach that aimed to achieve minimal disease activity, which included the use of TNF inhibitors.
Much research on TNF inhibitors during pregnancy has been limited to the first trimester and focused primarily on congenital malformations. In addition, most previous studies evaluating TNF inhibitors during pregnancy involved patients with different underlying diseases, making it difficult to interpret the results.
Hieronymus T. W. Smeele, MD, and colleagues at Erasmus University Medical Center, Rotterdam, the Netherlands, evaluated participants every 3 months before pregnancy; then again in the first, second, and third trimesters; and at 6, 12, and 26 weeks post partum. At these visits, in addition to undergoing an examination of their joints, patients completed questionnaires and gave blood samples. Disease activity was determined using the Disease Activity Score in 28 joints. Twin births and diagnoses other than RA were excluded.
Bigger babies
The study found that use of TNF inhibitors during pregnancy (n = 92 women) did not increase the risk of birth defects or emergency cesarean sections. While RA is typically associated with small-for-gestational-age (SGA) birth weights, TNF inhibitors were associated with a significant increase in birth weight and fewer infants born SGA, even when the comparison was adjusted for confounders, such as disease activity. At the same time, TNF inhibitors were not associated with high birth weight or with infants who were large for gestational age (LGA).
The results showed that the effects were greatest when TNF inhibitors were used in the third trimester. However, teasing out the effects based on trimester is difficult because participants who used TNF inhibitors during the third trimester were likely to use them in the first and second trimester as well. The study’s authors pointed out that these results need to be replicated.
“The immune system is not only important in the pathogenesis of RA,” the study’s authors wrote, “but also for ensuring and maintaining a normal pregnancy.” They pointed out that many adverse outcomes of pregnancy that are thought to arise from inadequate development of the placenta, such as intrauterine growth restriction, SGA, and hypertensive disorders of pregnancy, can involve an increase in proinflammatory cytokines, such as TNF. “It is tempting to speculate that treatment with [TNF inhibitors] during pregnancy promotes placentation and thereby fetal growth and birth weight by changing the balance between proinflammatory and anti-inflammatory cytokines and by increasing the number and function of [regulatory T cells].” They also hypothesize that treatment with TNF inhibitors induces epigenetic changes in the fetus, which positively influence fetal growth.
Welcomed data
This is a well-done, interesting study that will add to the still-slim body of research on pregnancy in rheumatic diseases, Kevin Byram, MD, assistant professor of medicine in the division of rheumatology and immunology and associate director of the rheumatology training program at Vanderbilt University, Nashville, Tenn., told this news organization.
“Historically, pregnant women have been excluded from clinical trials, not just in rheumatoid arthritis, but in other rheumatic diseases, so we don’t have a lot of great data,” he said, adding that the more interesting part of the study was that it showed there was no increased risk of adverse outcomes. “I’m not sure what to make of the increased birth weight. It will be interesting to see if the hypothesis that there might be a role for this molecule in preventing low birth weight goes anywhere.”
The work was supported by the Dutch Arthritis Foundation. PreCARA is an investigator-initiated study that was financially supported by UCB. The authors declared no competing interests.
A version of this article first appeared on Medscape.com.
Women with well-controlled rheumatoid arthritis who used a tumor necrosis factor (TNF) inhibitor during pregnancy gave birth to infants with higher birth weight than did other patients, without an increased risk of adverse outcomes, according to findings from a Dutch prospective cohort study published online in Annals of the Rheumatic Diseases.
The study involved 188 patients drawn from the ongoing Preconceptional Counseling in Active RA (PreCARA) study, which followed patients with inflammatory rheumatic diseases before and during pregnancy. Women enrolled in PreCARA were closely monitored and treated with a therapeutic approach that aimed to achieve minimal disease activity, which included the use of TNF inhibitors.
Much research on TNF inhibitors during pregnancy has been limited to the first trimester and focused primarily on congenital malformations. In addition, most previous studies evaluating TNF inhibitors during pregnancy involved patients with different underlying diseases, making it difficult to interpret the results.
Hieronymus T. W. Smeele, MD, and colleagues at Erasmus University Medical Center, Rotterdam, the Netherlands, evaluated participants every 3 months before pregnancy; then again in the first, second, and third trimesters; and at 6, 12, and 26 weeks post partum. At these visits, in addition to undergoing an examination of their joints, patients completed questionnaires and gave blood samples. Disease activity was determined using the Disease Activity Score in 28 joints. Twin births and diagnoses other than RA were excluded.
Bigger babies
The study found that use of TNF inhibitors during pregnancy (n = 92 women) did not increase the risk of birth defects or emergency cesarean sections. While RA is typically associated with small-for-gestational-age (SGA) birth weights, TNF inhibitors were associated with a significant increase in birth weight and fewer infants born SGA, even when the comparison was adjusted for confounders, such as disease activity. At the same time, TNF inhibitors were not associated with high birth weight or with infants who were large for gestational age (LGA).
The results showed that the effects were greatest when TNF inhibitors were used in the third trimester. However, teasing out the effects based on trimester is difficult because participants who used TNF inhibitors during the third trimester were likely to use them in the first and second trimester as well. The study’s authors pointed out that these results need to be replicated.
“The immune system is not only important in the pathogenesis of RA,” the study’s authors wrote, “but also for ensuring and maintaining a normal pregnancy.” They pointed out that many adverse outcomes of pregnancy that are thought to arise from inadequate development of the placenta, such as intrauterine growth restriction, SGA, and hypertensive disorders of pregnancy, can involve an increase in proinflammatory cytokines, such as TNF. “It is tempting to speculate that treatment with [TNF inhibitors] during pregnancy promotes placentation and thereby fetal growth and birth weight by changing the balance between proinflammatory and anti-inflammatory cytokines and by increasing the number and function of [regulatory T cells].” They also hypothesize that treatment with TNF inhibitors induces epigenetic changes in the fetus, which positively influence fetal growth.
Welcomed data
This is a well-done, interesting study that will add to the still-slim body of research on pregnancy in rheumatic diseases, Kevin Byram, MD, assistant professor of medicine in the division of rheumatology and immunology and associate director of the rheumatology training program at Vanderbilt University, Nashville, Tenn., told this news organization.
“Historically, pregnant women have been excluded from clinical trials, not just in rheumatoid arthritis, but in other rheumatic diseases, so we don’t have a lot of great data,” he said, adding that the more interesting part of the study was that it showed there was no increased risk of adverse outcomes. “I’m not sure what to make of the increased birth weight. It will be interesting to see if the hypothesis that there might be a role for this molecule in preventing low birth weight goes anywhere.”
The work was supported by the Dutch Arthritis Foundation. PreCARA is an investigator-initiated study that was financially supported by UCB. The authors declared no competing interests.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF THE RHEUMATIC DISEASES
Alcohol-related cirrhosis associated with higher risk of fractures, death
Patients with alcohol-related cirrhosis have a higher fracture rate and a higher post-fracture mortality rate, compared with the general population, according to a large new study from Sweden.
Alcohol-related cirrhosis was associated with an almost fourfold increased fracture rate, and the post-fracture mortality rates were higher at both 30 days and 1 year later.
“Half of all fractures were presumably associated with osteoporosis,” write the study authors, who are gastroenterologists and epidemiologists at the Karolinska Institute, Stockholm. “This suggests that existing pharmacotherapy for osteoporosis may reduce the fracture risk in patients with alcohol-related cirrhosis and possibly also reduce mortality rates.”
But, the authors continue, “our data indicate that osteoporosis may not be the only explanatory factor for this increased fracture risk. Removing modifiable risk factors such as smoking, heavy alcohol use, or malnutrition may further reduce the risk of fractures.”
The study was published online in Clinical Gastroenterology and Hepatology.
Analyzing risks
The association between liver cirrhosis and fractures appears strongest in patients with alcohol-related cirrhosis, the most common cause of cirrhosis in many countries, including Sweden, the authors write.
Previous studies have examined mostly relative risk or hip fractures. The authors aimed to determine not only the relative risk but also the absolute risk, which “can better inform clinicians and policymakers of the actual size of the problem,” they write.
In a nationwide population-based cohort study, they analyzed data from the Swedish National Patient Registry between 1969 and 2016, which included 25,090 patients with alcohol-related cirrhosis. Patients were matched for sex, age, and municipality with 239,458 controls from the Swedish Total Population Registry. They calculated the cumulative incidence of fractures and accounted for competing risks, such as death or liver transportation.
Overall, 48,635 fractures occurred during 3.4 million person-years of follow-up, including 3,659 (14.6%) among patients and 44,976 (18.8%) among controls.
Patients with alcohol-related cirrhosis had a 3.8-times higher fracture rate, with 38.7 fractures per 1,000 person-years, compared with 13.3 in controls. Alcohol-related cirrhosis was also associated with a 1.9-times higher fracture rate than nonalcoholic cirrhosis and a 1.3-times higher fracture rate than noncirrhotic alcohol-related liver disease.
The cumulative incidence of fractures was elevated for patients with alcohol-related cirrhosis in the first 19 years of follow-up, with a 5-year risk at nearly 10%, compared with 4.5% for controls, and a 10-year risk of 13.5%, compared with 8.7% for controls.
Among those with a fracture, the median time to death was 2.8 years in patients with alcohol-related cirrhosis and 3.5 years in controls.
Patients with alcohol-related cirrhosis had a 1.6-times higher post-fracture mortality rate at 30 days, as well as a 1.8-times higher post-fracture mortality rate after one year.
“Falls and fractures kill patients with cirrhosis. Data like these are crucial to spread awareness and represent a call to arms,” Elliot Tapper, MD, an assistant professor of gastroenterology at the University of Michigan, Ann Arbor, told this news organization.
Dr. Tapper, who wasn’t involved with this study, researches the health outcomes of patients with cirrhosis. His previous studies have found that falls, injuries, and death are common in patients with cirrhosis, which could be predicted with an algorithm based on a prior history of falls, blood sodium level, mobility, and quality of life.
“The data emphasize that a fall and fracture herald a time of increased risk,” he said. “Research is needed to develop interventions that prevent falls and help patients remain more resilient when they happen.”
Promoting bone health
Osteoporosis was the most common presumed mechanism in both patients with alcohol-related cirrhosis (49.4%) and controls (52.2%), while high-energy trauma from motor vehicle crashes or heights preceded 10.9% of fractures in patients and 13.5% in controls.
The Karolinska Institute study found that patients with alcohol-related cirrhosis had a 4.4-times higher rate of osteoporotic fracture than controls, which remained 3.6-times higher when using a stricter definition of osteoporotic fracture (a diagnosis of osteoporosis before, at, or within 3 months from the date of a fracture of the vertebrae, pelvis, proximal humerus, distal forearm, or hip).
Patients with osteoporosis at baseline had a 2.5-times higher incidence of fractures than controls with baseline osteoporosis. The absolute risk of fractures in patients with alcohol-related cirrhosis and osteoporosis was higher than for controls with osteoporosis during the first 3 years after a cirrhosis diagnosis.
In addition, the post-fracture mortality rate in those with osteoporosis was more than double in patients with cirrhosis in the first 30 days after a fracture and more than tripled after one year.
“Bone health isn’t necessarily prioritized for our patients, even though it is linked to higher mortality and disability,” Arpan Patel, MD, PhD, a hepatologist at the West Los Angeles VA Medical Center and assistant professor at the David Geffen School of Medicine at the University of California, Los Angeles, told this news organization.
Dr. Patel, who wasn’t involved with this study, has researched the associations between osteoporotic fracture risk, hospitalization, and death in patients with cirrhosis.
“Current guidelines support assessing post-liver transplant patients for bone density but do not currently advocate for doing so in patients with cirrhosis or alcohol-associated liver disease, who are a much larger at-risk population,” Dr. Patel said.
“The current paper supports the idea that we should consider the broad ramifications of alcohol use on bone health for our patients and suggests that there should be greater efforts to screen for and manage osteoporosis and osteopenia in our patients earlier,” he added.
The researchers were supported by grants from Region Stockholm and the Syskonen Svensson Foundation, though the funders had no role in the conduct of the study. The study authors reported no other disclosures or conflicts of interest. Dr. Tapper and Dr. Patel report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients with alcohol-related cirrhosis have a higher fracture rate and a higher post-fracture mortality rate, compared with the general population, according to a large new study from Sweden.
Alcohol-related cirrhosis was associated with an almost fourfold increased fracture rate, and the post-fracture mortality rates were higher at both 30 days and 1 year later.
“Half of all fractures were presumably associated with osteoporosis,” write the study authors, who are gastroenterologists and epidemiologists at the Karolinska Institute, Stockholm. “This suggests that existing pharmacotherapy for osteoporosis may reduce the fracture risk in patients with alcohol-related cirrhosis and possibly also reduce mortality rates.”
But, the authors continue, “our data indicate that osteoporosis may not be the only explanatory factor for this increased fracture risk. Removing modifiable risk factors such as smoking, heavy alcohol use, or malnutrition may further reduce the risk of fractures.”
The study was published online in Clinical Gastroenterology and Hepatology.
Analyzing risks
The association between liver cirrhosis and fractures appears strongest in patients with alcohol-related cirrhosis, the most common cause of cirrhosis in many countries, including Sweden, the authors write.
Previous studies have examined mostly relative risk or hip fractures. The authors aimed to determine not only the relative risk but also the absolute risk, which “can better inform clinicians and policymakers of the actual size of the problem,” they write.
In a nationwide population-based cohort study, they analyzed data from the Swedish National Patient Registry between 1969 and 2016, which included 25,090 patients with alcohol-related cirrhosis. Patients were matched for sex, age, and municipality with 239,458 controls from the Swedish Total Population Registry. They calculated the cumulative incidence of fractures and accounted for competing risks, such as death or liver transportation.
Overall, 48,635 fractures occurred during 3.4 million person-years of follow-up, including 3,659 (14.6%) among patients and 44,976 (18.8%) among controls.
Patients with alcohol-related cirrhosis had a 3.8-times higher fracture rate, with 38.7 fractures per 1,000 person-years, compared with 13.3 in controls. Alcohol-related cirrhosis was also associated with a 1.9-times higher fracture rate than nonalcoholic cirrhosis and a 1.3-times higher fracture rate than noncirrhotic alcohol-related liver disease.
The cumulative incidence of fractures was elevated for patients with alcohol-related cirrhosis in the first 19 years of follow-up, with a 5-year risk at nearly 10%, compared with 4.5% for controls, and a 10-year risk of 13.5%, compared with 8.7% for controls.
Among those with a fracture, the median time to death was 2.8 years in patients with alcohol-related cirrhosis and 3.5 years in controls.
Patients with alcohol-related cirrhosis had a 1.6-times higher post-fracture mortality rate at 30 days, as well as a 1.8-times higher post-fracture mortality rate after one year.
“Falls and fractures kill patients with cirrhosis. Data like these are crucial to spread awareness and represent a call to arms,” Elliot Tapper, MD, an assistant professor of gastroenterology at the University of Michigan, Ann Arbor, told this news organization.
Dr. Tapper, who wasn’t involved with this study, researches the health outcomes of patients with cirrhosis. His previous studies have found that falls, injuries, and death are common in patients with cirrhosis, which could be predicted with an algorithm based on a prior history of falls, blood sodium level, mobility, and quality of life.
“The data emphasize that a fall and fracture herald a time of increased risk,” he said. “Research is needed to develop interventions that prevent falls and help patients remain more resilient when they happen.”
Promoting bone health
Osteoporosis was the most common presumed mechanism in both patients with alcohol-related cirrhosis (49.4%) and controls (52.2%), while high-energy trauma from motor vehicle crashes or heights preceded 10.9% of fractures in patients and 13.5% in controls.
The Karolinska Institute study found that patients with alcohol-related cirrhosis had a 4.4-times higher rate of osteoporotic fracture than controls, which remained 3.6-times higher when using a stricter definition of osteoporotic fracture (a diagnosis of osteoporosis before, at, or within 3 months from the date of a fracture of the vertebrae, pelvis, proximal humerus, distal forearm, or hip).
Patients with osteoporosis at baseline had a 2.5-times higher incidence of fractures than controls with baseline osteoporosis. The absolute risk of fractures in patients with alcohol-related cirrhosis and osteoporosis was higher than for controls with osteoporosis during the first 3 years after a cirrhosis diagnosis.
In addition, the post-fracture mortality rate in those with osteoporosis was more than double in patients with cirrhosis in the first 30 days after a fracture and more than tripled after one year.
“Bone health isn’t necessarily prioritized for our patients, even though it is linked to higher mortality and disability,” Arpan Patel, MD, PhD, a hepatologist at the West Los Angeles VA Medical Center and assistant professor at the David Geffen School of Medicine at the University of California, Los Angeles, told this news organization.
Dr. Patel, who wasn’t involved with this study, has researched the associations between osteoporotic fracture risk, hospitalization, and death in patients with cirrhosis.
“Current guidelines support assessing post-liver transplant patients for bone density but do not currently advocate for doing so in patients with cirrhosis or alcohol-associated liver disease, who are a much larger at-risk population,” Dr. Patel said.
“The current paper supports the idea that we should consider the broad ramifications of alcohol use on bone health for our patients and suggests that there should be greater efforts to screen for and manage osteoporosis and osteopenia in our patients earlier,” he added.
The researchers were supported by grants from Region Stockholm and the Syskonen Svensson Foundation, though the funders had no role in the conduct of the study. The study authors reported no other disclosures or conflicts of interest. Dr. Tapper and Dr. Patel report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients with alcohol-related cirrhosis have a higher fracture rate and a higher post-fracture mortality rate, compared with the general population, according to a large new study from Sweden.
Alcohol-related cirrhosis was associated with an almost fourfold increased fracture rate, and the post-fracture mortality rates were higher at both 30 days and 1 year later.
“Half of all fractures were presumably associated with osteoporosis,” write the study authors, who are gastroenterologists and epidemiologists at the Karolinska Institute, Stockholm. “This suggests that existing pharmacotherapy for osteoporosis may reduce the fracture risk in patients with alcohol-related cirrhosis and possibly also reduce mortality rates.”
But, the authors continue, “our data indicate that osteoporosis may not be the only explanatory factor for this increased fracture risk. Removing modifiable risk factors such as smoking, heavy alcohol use, or malnutrition may further reduce the risk of fractures.”
The study was published online in Clinical Gastroenterology and Hepatology.
Analyzing risks
The association between liver cirrhosis and fractures appears strongest in patients with alcohol-related cirrhosis, the most common cause of cirrhosis in many countries, including Sweden, the authors write.
Previous studies have examined mostly relative risk or hip fractures. The authors aimed to determine not only the relative risk but also the absolute risk, which “can better inform clinicians and policymakers of the actual size of the problem,” they write.
In a nationwide population-based cohort study, they analyzed data from the Swedish National Patient Registry between 1969 and 2016, which included 25,090 patients with alcohol-related cirrhosis. Patients were matched for sex, age, and municipality with 239,458 controls from the Swedish Total Population Registry. They calculated the cumulative incidence of fractures and accounted for competing risks, such as death or liver transportation.
Overall, 48,635 fractures occurred during 3.4 million person-years of follow-up, including 3,659 (14.6%) among patients and 44,976 (18.8%) among controls.
Patients with alcohol-related cirrhosis had a 3.8-times higher fracture rate, with 38.7 fractures per 1,000 person-years, compared with 13.3 in controls. Alcohol-related cirrhosis was also associated with a 1.9-times higher fracture rate than nonalcoholic cirrhosis and a 1.3-times higher fracture rate than noncirrhotic alcohol-related liver disease.
The cumulative incidence of fractures was elevated for patients with alcohol-related cirrhosis in the first 19 years of follow-up, with a 5-year risk at nearly 10%, compared with 4.5% for controls, and a 10-year risk of 13.5%, compared with 8.7% for controls.
Among those with a fracture, the median time to death was 2.8 years in patients with alcohol-related cirrhosis and 3.5 years in controls.
Patients with alcohol-related cirrhosis had a 1.6-times higher post-fracture mortality rate at 30 days, as well as a 1.8-times higher post-fracture mortality rate after one year.
“Falls and fractures kill patients with cirrhosis. Data like these are crucial to spread awareness and represent a call to arms,” Elliot Tapper, MD, an assistant professor of gastroenterology at the University of Michigan, Ann Arbor, told this news organization.
Dr. Tapper, who wasn’t involved with this study, researches the health outcomes of patients with cirrhosis. His previous studies have found that falls, injuries, and death are common in patients with cirrhosis, which could be predicted with an algorithm based on a prior history of falls, blood sodium level, mobility, and quality of life.
“The data emphasize that a fall and fracture herald a time of increased risk,” he said. “Research is needed to develop interventions that prevent falls and help patients remain more resilient when they happen.”
Promoting bone health
Osteoporosis was the most common presumed mechanism in both patients with alcohol-related cirrhosis (49.4%) and controls (52.2%), while high-energy trauma from motor vehicle crashes or heights preceded 10.9% of fractures in patients and 13.5% in controls.
The Karolinska Institute study found that patients with alcohol-related cirrhosis had a 4.4-times higher rate of osteoporotic fracture than controls, which remained 3.6-times higher when using a stricter definition of osteoporotic fracture (a diagnosis of osteoporosis before, at, or within 3 months from the date of a fracture of the vertebrae, pelvis, proximal humerus, distal forearm, or hip).
Patients with osteoporosis at baseline had a 2.5-times higher incidence of fractures than controls with baseline osteoporosis. The absolute risk of fractures in patients with alcohol-related cirrhosis and osteoporosis was higher than for controls with osteoporosis during the first 3 years after a cirrhosis diagnosis.
In addition, the post-fracture mortality rate in those with osteoporosis was more than double in patients with cirrhosis in the first 30 days after a fracture and more than tripled after one year.
“Bone health isn’t necessarily prioritized for our patients, even though it is linked to higher mortality and disability,” Arpan Patel, MD, PhD, a hepatologist at the West Los Angeles VA Medical Center and assistant professor at the David Geffen School of Medicine at the University of California, Los Angeles, told this news organization.
Dr. Patel, who wasn’t involved with this study, has researched the associations between osteoporotic fracture risk, hospitalization, and death in patients with cirrhosis.
“Current guidelines support assessing post-liver transplant patients for bone density but do not currently advocate for doing so in patients with cirrhosis or alcohol-associated liver disease, who are a much larger at-risk population,” Dr. Patel said.
“The current paper supports the idea that we should consider the broad ramifications of alcohol use on bone health for our patients and suggests that there should be greater efforts to screen for and manage osteoporosis and osteopenia in our patients earlier,” he added.
The researchers were supported by grants from Region Stockholm and the Syskonen Svensson Foundation, though the funders had no role in the conduct of the study. The study authors reported no other disclosures or conflicts of interest. Dr. Tapper and Dr. Patel report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
RADIANCE II: Positive signal for ultrasound renal denervation
Top-line results released on July 26 from the RADIANCE II trial show the Paradise ultrasound renal denervation system significantly reduces daytime ambulatory systolic blood pressure, compared with a sham procedure at 2 months in patients with mild to moderate uncontrolled hypertension.
The trial was conducted in 224 patients who were previously treated with up to two medications and were randomized while off medication at more than 60 centers in 8 countries. No further details or results were provided.
The pivotal RADIANCE II trial, required for FDA approval, is the third and largest randomized, sham-controlled study following positive results reported by RADIANCE-HTN SOLO and RADIANCE-HTN TRIO, ReCor Medical and its subsidiary Otsuka Medical Devices noted in the announcement.
The field of renal denervation fell out of favor after the largest trial in 535 patients, SYMPLICITY HTN-3, failed to show a significant reduction in systolic blood pressure at 6 months, compared with sham control in resistant hypertension.
A version of this article first appeared on Medscape.com.
Top-line results released on July 26 from the RADIANCE II trial show the Paradise ultrasound renal denervation system significantly reduces daytime ambulatory systolic blood pressure, compared with a sham procedure at 2 months in patients with mild to moderate uncontrolled hypertension.
The trial was conducted in 224 patients who were previously treated with up to two medications and were randomized while off medication at more than 60 centers in 8 countries. No further details or results were provided.
The pivotal RADIANCE II trial, required for FDA approval, is the third and largest randomized, sham-controlled study following positive results reported by RADIANCE-HTN SOLO and RADIANCE-HTN TRIO, ReCor Medical and its subsidiary Otsuka Medical Devices noted in the announcement.
The field of renal denervation fell out of favor after the largest trial in 535 patients, SYMPLICITY HTN-3, failed to show a significant reduction in systolic blood pressure at 6 months, compared with sham control in resistant hypertension.
A version of this article first appeared on Medscape.com.
Top-line results released on July 26 from the RADIANCE II trial show the Paradise ultrasound renal denervation system significantly reduces daytime ambulatory systolic blood pressure, compared with a sham procedure at 2 months in patients with mild to moderate uncontrolled hypertension.
The trial was conducted in 224 patients who were previously treated with up to two medications and were randomized while off medication at more than 60 centers in 8 countries. No further details or results were provided.
The pivotal RADIANCE II trial, required for FDA approval, is the third and largest randomized, sham-controlled study following positive results reported by RADIANCE-HTN SOLO and RADIANCE-HTN TRIO, ReCor Medical and its subsidiary Otsuka Medical Devices noted in the announcement.
The field of renal denervation fell out of favor after the largest trial in 535 patients, SYMPLICITY HTN-3, failed to show a significant reduction in systolic blood pressure at 6 months, compared with sham control in resistant hypertension.
A version of this article first appeared on Medscape.com.
Vitamin D supplements do not lower risk of fractures
compared with placebo, according to results from an ancillary study of the Vitamin D and Omega-3 Trial (VITAL).
The data showed that taking 2,000 IU of supplemental vitamin D each day without coadministered calcium did not have a significant effect on nonvertebral fractures (hazard ratio, 0.97; P = .50), hip fractures (HR, 1.01; P = .96), or total fractures (HR, 0.98; P = .70), compared with taking placebo, among individuals who did not have osteoporosis, vitamin D deficiency, or low bone mass, report Meryl S. LeBoff, MD, a professor of medicine at Harvard Medical School and chief of the calcium and bone section at Brigham and Women’s Hospital, both in Boston, and colleagues.
The findings were published online in the New England Journal of Medicine.
Prior randomized, controlled trials have presented conflicting findings. Some have shown that there is some benefit to supplemental vitamin D, whereas others have shown no effect or even harm with regard to risk of fractures, Dr. LeBoff noted.
“Because of the conflicting data at the time, we tested this hypothesis in an effort to advance science and understanding of the effects of vitamin D on bone. In a previous study, we did not see an effect of supplemental vitamin D on bone density in a subcohort from the VITAL trial,” Dr. LeBoff said in an interview.
“We previously reported that vitamin D, about 2,000 units per day, did not increase bone density, nor did it affect bone structure, according to PQCT [peripheral quantitative CT]. So that was an indicator that since bone density is a surrogate marker of fractures, there may not be an effect on fractures,” she added.
These results should dispel any idea that vitamin D alone could significantly reduce fracture rates in the general population, noted Steven R. Cummings, MD, of the University of California, San Francisco, and Clifford Rosen, MD, of Maine Medical Center Research Institute, Scarborough, in an accompanying editorial.
“Adding those findings to previous reports from VITAL and other trials showing the lack of an effect for preventing numerous conditions suggests that providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life,” the editorialists wrote.
The researchers assessed 25,871 participants from all 50 states during a median follow-up time of 5.3 years. Participants were randomly assigned in a 1:1 ratio to receive placebo or vitamin D.
The mean age of the participants was 67.1 years; 50.6% of the study cohort were women, and 20.2% of the cohort were Black. Participants did not have low bone mass, vitamin D deficiency, or osteoporosis.
Participants agreed not to supplement their dietary intake with more than 1,200 mg of calcium each day and no more than 800 IU of vitamin D each day.
Participants filled out detailed surveys to evaluate baseline prescription drug use, demographic factors, medical history, and the consumption of supplements, such as fish oil, calcium, and vitamin D, during the run-in stage. Yearly surveys were used to assess side effects, adherence to the investigation protocol, falls, fractures, physical activity, osteoporosis and associated risk factors, onset of major illness, and the use of nontrial prescription drugs and supplements, such as vitamin D and calcium.
The researchers adjudicated incident fracture data using a centralized medical record review. To approximate the therapeutic effect in intention-to-treat analyses, they used proportional-hazard models.
Notably, outcomes were similar for the placebo and vitamin D groups with regard to incident kidney stones and hypercalcemia.
The effect of vitamin D supplementation was not modified by baseline parameters such as race or ethnicity, sex, body mass index, age, or blood 25-hydroxyvitamin D levels.
Dr. Cummings and Dr. Rosen pointed out that these findings, along with other VITAL trial data, show that no subgroups classified on the basis of baseline 25-hydroxyvitamin D levels, including those with levels less than 20 ng/mL, benefited from vitamin supplementation.
“There is no justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level. A 25-hydroxyvitamin D level might be a useful diagnostic test for some patients with conditions that may be due to or that may cause severe deficiency,” the editorialists noted.
Except with regard to select patients, such as individuals living in nursing homes who have limited sun exposure, the use of the terms “vitamin D deficiency” and “vitamin D “insufficiency” should now be reevaluated, Dr. Rosen and Dr. Cummings wrote.
The study’s limitations include its assessment of only one dosage of vitamin D supplementation and a lack of adjustment for multiplicity, exploratory, parent trial, or secondary endpoints, the researchers noted.
The number of participants who had vitamin D deficiency was limited, owing to ethical and feasibility concerns regarding these patients. The data are not generalizable to individuals who are older and institutionalized or those who have osteomalacia or osteoporosis, the researchers wrote.
Expert commentary
“The interpretation of this [study] to me is that vitamin D is not for everybody,” said Baha Arafah, MD, professor of medicine at Case Western Reserve University and chief of the division of endocrinology at University Hospital, both in Cleveland, who was not involved in the study.
“This is not the final word; I would suggest that you don’t throw vitamin D at everybody. I would use markers of bone formation as a better measure to determine whether they need vitamin D or not, specifically looking at parathyroid hormone,” Dr. Arafah said in an interview.
Dr. Arafah pointed out that these data do not mean that clinicians should stop thinking about vitamin D altogether. “I think that would be the wrong message to read. If you read through the article, you will find that there are people who do need vitamin D; people who are deficient do need vitamin D. There’s no question that excessive or extreme vitamin D deficiency can lead to other things, specifically, osteomalacia, weak bones, [and] poor mineralization, so we are not totally out of the woods at this time.”
The ancillary study of the VITAL trial was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Pharmavite donated the vitamin D 3 supplements used in the trial. Dr. LeBoff reported that she holds stock in Amgen. Cummings reported receiving personal fees and nonfinancial support from Amgen outside the submitted work. Dr. Rosen is associate editor of the New England Journal of Medicine. Dr. Arafah reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
compared with placebo, according to results from an ancillary study of the Vitamin D and Omega-3 Trial (VITAL).
The data showed that taking 2,000 IU of supplemental vitamin D each day without coadministered calcium did not have a significant effect on nonvertebral fractures (hazard ratio, 0.97; P = .50), hip fractures (HR, 1.01; P = .96), or total fractures (HR, 0.98; P = .70), compared with taking placebo, among individuals who did not have osteoporosis, vitamin D deficiency, or low bone mass, report Meryl S. LeBoff, MD, a professor of medicine at Harvard Medical School and chief of the calcium and bone section at Brigham and Women’s Hospital, both in Boston, and colleagues.
The findings were published online in the New England Journal of Medicine.
Prior randomized, controlled trials have presented conflicting findings. Some have shown that there is some benefit to supplemental vitamin D, whereas others have shown no effect or even harm with regard to risk of fractures, Dr. LeBoff noted.
“Because of the conflicting data at the time, we tested this hypothesis in an effort to advance science and understanding of the effects of vitamin D on bone. In a previous study, we did not see an effect of supplemental vitamin D on bone density in a subcohort from the VITAL trial,” Dr. LeBoff said in an interview.
“We previously reported that vitamin D, about 2,000 units per day, did not increase bone density, nor did it affect bone structure, according to PQCT [peripheral quantitative CT]. So that was an indicator that since bone density is a surrogate marker of fractures, there may not be an effect on fractures,” she added.
These results should dispel any idea that vitamin D alone could significantly reduce fracture rates in the general population, noted Steven R. Cummings, MD, of the University of California, San Francisco, and Clifford Rosen, MD, of Maine Medical Center Research Institute, Scarborough, in an accompanying editorial.
“Adding those findings to previous reports from VITAL and other trials showing the lack of an effect for preventing numerous conditions suggests that providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life,” the editorialists wrote.
The researchers assessed 25,871 participants from all 50 states during a median follow-up time of 5.3 years. Participants were randomly assigned in a 1:1 ratio to receive placebo or vitamin D.
The mean age of the participants was 67.1 years; 50.6% of the study cohort were women, and 20.2% of the cohort were Black. Participants did not have low bone mass, vitamin D deficiency, or osteoporosis.
Participants agreed not to supplement their dietary intake with more than 1,200 mg of calcium each day and no more than 800 IU of vitamin D each day.
Participants filled out detailed surveys to evaluate baseline prescription drug use, demographic factors, medical history, and the consumption of supplements, such as fish oil, calcium, and vitamin D, during the run-in stage. Yearly surveys were used to assess side effects, adherence to the investigation protocol, falls, fractures, physical activity, osteoporosis and associated risk factors, onset of major illness, and the use of nontrial prescription drugs and supplements, such as vitamin D and calcium.
The researchers adjudicated incident fracture data using a centralized medical record review. To approximate the therapeutic effect in intention-to-treat analyses, they used proportional-hazard models.
Notably, outcomes were similar for the placebo and vitamin D groups with regard to incident kidney stones and hypercalcemia.
The effect of vitamin D supplementation was not modified by baseline parameters such as race or ethnicity, sex, body mass index, age, or blood 25-hydroxyvitamin D levels.
Dr. Cummings and Dr. Rosen pointed out that these findings, along with other VITAL trial data, show that no subgroups classified on the basis of baseline 25-hydroxyvitamin D levels, including those with levels less than 20 ng/mL, benefited from vitamin supplementation.
“There is no justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level. A 25-hydroxyvitamin D level might be a useful diagnostic test for some patients with conditions that may be due to or that may cause severe deficiency,” the editorialists noted.
Except with regard to select patients, such as individuals living in nursing homes who have limited sun exposure, the use of the terms “vitamin D deficiency” and “vitamin D “insufficiency” should now be reevaluated, Dr. Rosen and Dr. Cummings wrote.
The study’s limitations include its assessment of only one dosage of vitamin D supplementation and a lack of adjustment for multiplicity, exploratory, parent trial, or secondary endpoints, the researchers noted.
The number of participants who had vitamin D deficiency was limited, owing to ethical and feasibility concerns regarding these patients. The data are not generalizable to individuals who are older and institutionalized or those who have osteomalacia or osteoporosis, the researchers wrote.
Expert commentary
“The interpretation of this [study] to me is that vitamin D is not for everybody,” said Baha Arafah, MD, professor of medicine at Case Western Reserve University and chief of the division of endocrinology at University Hospital, both in Cleveland, who was not involved in the study.
“This is not the final word; I would suggest that you don’t throw vitamin D at everybody. I would use markers of bone formation as a better measure to determine whether they need vitamin D or not, specifically looking at parathyroid hormone,” Dr. Arafah said in an interview.
Dr. Arafah pointed out that these data do not mean that clinicians should stop thinking about vitamin D altogether. “I think that would be the wrong message to read. If you read through the article, you will find that there are people who do need vitamin D; people who are deficient do need vitamin D. There’s no question that excessive or extreme vitamin D deficiency can lead to other things, specifically, osteomalacia, weak bones, [and] poor mineralization, so we are not totally out of the woods at this time.”
The ancillary study of the VITAL trial was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Pharmavite donated the vitamin D 3 supplements used in the trial. Dr. LeBoff reported that she holds stock in Amgen. Cummings reported receiving personal fees and nonfinancial support from Amgen outside the submitted work. Dr. Rosen is associate editor of the New England Journal of Medicine. Dr. Arafah reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
compared with placebo, according to results from an ancillary study of the Vitamin D and Omega-3 Trial (VITAL).
The data showed that taking 2,000 IU of supplemental vitamin D each day without coadministered calcium did not have a significant effect on nonvertebral fractures (hazard ratio, 0.97; P = .50), hip fractures (HR, 1.01; P = .96), or total fractures (HR, 0.98; P = .70), compared with taking placebo, among individuals who did not have osteoporosis, vitamin D deficiency, or low bone mass, report Meryl S. LeBoff, MD, a professor of medicine at Harvard Medical School and chief of the calcium and bone section at Brigham and Women’s Hospital, both in Boston, and colleagues.
The findings were published online in the New England Journal of Medicine.
Prior randomized, controlled trials have presented conflicting findings. Some have shown that there is some benefit to supplemental vitamin D, whereas others have shown no effect or even harm with regard to risk of fractures, Dr. LeBoff noted.
“Because of the conflicting data at the time, we tested this hypothesis in an effort to advance science and understanding of the effects of vitamin D on bone. In a previous study, we did not see an effect of supplemental vitamin D on bone density in a subcohort from the VITAL trial,” Dr. LeBoff said in an interview.
“We previously reported that vitamin D, about 2,000 units per day, did not increase bone density, nor did it affect bone structure, according to PQCT [peripheral quantitative CT]. So that was an indicator that since bone density is a surrogate marker of fractures, there may not be an effect on fractures,” she added.
These results should dispel any idea that vitamin D alone could significantly reduce fracture rates in the general population, noted Steven R. Cummings, MD, of the University of California, San Francisco, and Clifford Rosen, MD, of Maine Medical Center Research Institute, Scarborough, in an accompanying editorial.
“Adding those findings to previous reports from VITAL and other trials showing the lack of an effect for preventing numerous conditions suggests that providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life,” the editorialists wrote.
The researchers assessed 25,871 participants from all 50 states during a median follow-up time of 5.3 years. Participants were randomly assigned in a 1:1 ratio to receive placebo or vitamin D.
The mean age of the participants was 67.1 years; 50.6% of the study cohort were women, and 20.2% of the cohort were Black. Participants did not have low bone mass, vitamin D deficiency, or osteoporosis.
Participants agreed not to supplement their dietary intake with more than 1,200 mg of calcium each day and no more than 800 IU of vitamin D each day.
Participants filled out detailed surveys to evaluate baseline prescription drug use, demographic factors, medical history, and the consumption of supplements, such as fish oil, calcium, and vitamin D, during the run-in stage. Yearly surveys were used to assess side effects, adherence to the investigation protocol, falls, fractures, physical activity, osteoporosis and associated risk factors, onset of major illness, and the use of nontrial prescription drugs and supplements, such as vitamin D and calcium.
The researchers adjudicated incident fracture data using a centralized medical record review. To approximate the therapeutic effect in intention-to-treat analyses, they used proportional-hazard models.
Notably, outcomes were similar for the placebo and vitamin D groups with regard to incident kidney stones and hypercalcemia.
The effect of vitamin D supplementation was not modified by baseline parameters such as race or ethnicity, sex, body mass index, age, or blood 25-hydroxyvitamin D levels.
Dr. Cummings and Dr. Rosen pointed out that these findings, along with other VITAL trial data, show that no subgroups classified on the basis of baseline 25-hydroxyvitamin D levels, including those with levels less than 20 ng/mL, benefited from vitamin supplementation.
“There is no justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level. A 25-hydroxyvitamin D level might be a useful diagnostic test for some patients with conditions that may be due to or that may cause severe deficiency,” the editorialists noted.
Except with regard to select patients, such as individuals living in nursing homes who have limited sun exposure, the use of the terms “vitamin D deficiency” and “vitamin D “insufficiency” should now be reevaluated, Dr. Rosen and Dr. Cummings wrote.
The study’s limitations include its assessment of only one dosage of vitamin D supplementation and a lack of adjustment for multiplicity, exploratory, parent trial, or secondary endpoints, the researchers noted.
The number of participants who had vitamin D deficiency was limited, owing to ethical and feasibility concerns regarding these patients. The data are not generalizable to individuals who are older and institutionalized or those who have osteomalacia or osteoporosis, the researchers wrote.
Expert commentary
“The interpretation of this [study] to me is that vitamin D is not for everybody,” said Baha Arafah, MD, professor of medicine at Case Western Reserve University and chief of the division of endocrinology at University Hospital, both in Cleveland, who was not involved in the study.
“This is not the final word; I would suggest that you don’t throw vitamin D at everybody. I would use markers of bone formation as a better measure to determine whether they need vitamin D or not, specifically looking at parathyroid hormone,” Dr. Arafah said in an interview.
Dr. Arafah pointed out that these data do not mean that clinicians should stop thinking about vitamin D altogether. “I think that would be the wrong message to read. If you read through the article, you will find that there are people who do need vitamin D; people who are deficient do need vitamin D. There’s no question that excessive or extreme vitamin D deficiency can lead to other things, specifically, osteomalacia, weak bones, [and] poor mineralization, so we are not totally out of the woods at this time.”
The ancillary study of the VITAL trial was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Pharmavite donated the vitamin D 3 supplements used in the trial. Dr. LeBoff reported that she holds stock in Amgen. Cummings reported receiving personal fees and nonfinancial support from Amgen outside the submitted work. Dr. Rosen is associate editor of the New England Journal of Medicine. Dr. Arafah reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Medicare advantage tied to less use of pricey diabetes drugs
U.S. Medicare beneficiaries with type 2 diabetes who had health coverage through a Medicare Advantage (MA) plan received treatment with an sodium-glucose cotransporter 2 inhibitor or glucagonlike peptide–1 receptor agonist significantly less often than patients with traditional fee-for-service (FFS) Medicare coverage in 2014-2019, according to a study of more than 411,000 patients.
concluded Utibe R. Essien, MD, and coauthors in a study published in Diabetes Care.
The report comes as the U.S. Congress is looking closely at the MA program and evidence that insurance companies that provide these policies sometimes impose inappropriate barriers on enrolled beneficiaries by denying or limiting access to treatments and interventions in ways that run counter to Medicare’s coverage policies.
According to Representative Diana DeGette (D-Colo.), who chaired a hearing on MA plans on June 28 by the House of Representatives’ Energy and Commerce Subcommittee on Oversight and Investigations, beneficiaries who are covered through an MA plan “do not always get the care that they are entitled to.”
The study by Dr. Essien and colleagues also documents some positives of care delivered through MA plans for patients with type 2 diabetes, compared with what FFS Medicare beneficiaries generally receive, such as significantly higher rates of screening for nephropathy and ophthalmologic disorders, and foot examinations.
But the apparently dampened use of SGLT2 inhibitors and GLP-1 receptor agonists among MA beneficiaries stand out as notable shortcomings, Dr. Essien maintained.
Cost containment may limit use
“The differences in health outcomes and in treatments in MA plans are important to highlight,” Dr. Essien said in an interview. “We worry that the cost-containment challenges [associated with MA plans] may be limiting use of these newer treatments.”
The study was based on 2014-2019 data from the Diabetes Collaborative Registry, which collects information from more than 5,000 U.S. clinicians whose practices include patients with diabetes, as well as claims data recorded by the Centers for Medicare and Medicaid Services during 2014-2017.
The main analysis focused on 345,911 Medicare beneficiaries with diabetes, which included 34% with MA coverage and 66% with FFS coverage. The two subgroups had similar ages, about 75 years old, and roughly half were women in both subgroups. The rate at which both subgroups received statin treatment was nearly the same: 72% for those with MA coverage and 71% for those with FFS Medicare.
But MA beneficiaries differed from those with FFS coverage in several other ways. MA beneficiaries had a higher prevalence of Medicaid eligibility than the FFS group (20% vs 12%) and lower rates of consultations with cardiologists (41% vs. 45%) or endocrinologists (7% vs. 10%).
Some of the positive differences in the care received by MA beneficiaries, compared with FFS beneficiaries, after adjustment for potential clinical and sociodemographic confounders, included:
- Screening for nephropathy, at a significant 14% higher relative rate.
- Screening for ophthalmologic disorders, at a significant 8% higher relative rate.
- Undergoing a diabetic foot examination, at a significant 13% higher relative rate.
- Receiving smoking-cessation counseling, at a significant 5% higher relative rate.
- Receiving treatment with an ACE inhibitor or angiotensin-receptor blocker (87% vs. 81%).
- More consistently receiving treatment with metformin, with rates of 72% versus 69% in 2017.
However, these positive differences were accompanied by these relative shortcomings for those with MA, compared with FFS coverage:
- Lower rates of treatment with an SGLT2 inhibitor (5.4% vs. 6.7%), a significant 9% relative difference after adjustment.
- Lower rates of treatment with a GLP-1 agonist (6.9% vs. 9.0%), a significant 20% relative difference after adjustment.
- Higher average levels of LDL cholesterol (81.5 vs. 78.9 mg/dL), a significantly higher average hemoglobin A1c level (7.1% vs. 7.0%), and a trend toward a lower prevalence of blood pressure control (70.3% vs. 71.5%).
Researchers also highlight that the lower rate at which people with MA coverage received SGLT2 inhibitors or GLP-1 agonists was consistent in patients with established cardiovascular or kidney disease, for whom these agents are particularly recommended.
In addition, a secondary analysis of data for another 65,000 Medicare beneficiaries in 2018 and 2019 showed the disparity in use of agents from these two drug classes continued.
Low systemic use of SGLT2 inhibitors, GLP-1 agonists
Dr. Essien acknowledged that, even in people with FFS Medicare coverage, use of SGLT2 inhibitors and GLP-1 agonists was low, but the difference between those with MA coverage is “important.”
Researchers offered four factors that might drive reduced prescribing of agents from these two classes for patients with type 2 diabetes with MA coverage: cost-containment strategies put in place by MA plans; the lower rate of consultations with specialists (cardiologists and endocrinologists); possible exclusion of clinicians from MA provider networks who tend to prescribe these higher-price agents; and lower household incomes of people with MA plans, which may lead to cost-related nonadherence.
Most SGLT2 inhibitors have an average retail cost of about $6,000/year, and some GLP-1 agonists cost more than $10,000/year.
In general, MA coverage includes more oversight of care and its cost than occurs with FFS coverage, noted Dr. Essien, an internal medicine physician at the University of Pittsburgh and a researcher at the Center for Health Equity Research and Promotion of the VA Pittsburgh Healthcare System.
“Incentives for using these more expensive treatments may not be there in MA plans,” he explained. Overcoming cost-related barriers is a challenge that will require “bold policy changes,” as well as better education of clinicians so they make correct treatment decisions, and of patients to resolve possible concerns about treatment safety.
Rep. DeGette hinted during her remarks at the June hearing that policy changes may be coming from Congress.
“Our seniors and their doctors should not be required to jump through numerous hoops to get coverage for straightforward and medically necessary procedures,” she said.
The study received no commercial funding. Dr. Essien reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
U.S. Medicare beneficiaries with type 2 diabetes who had health coverage through a Medicare Advantage (MA) plan received treatment with an sodium-glucose cotransporter 2 inhibitor or glucagonlike peptide–1 receptor agonist significantly less often than patients with traditional fee-for-service (FFS) Medicare coverage in 2014-2019, according to a study of more than 411,000 patients.
concluded Utibe R. Essien, MD, and coauthors in a study published in Diabetes Care.
The report comes as the U.S. Congress is looking closely at the MA program and evidence that insurance companies that provide these policies sometimes impose inappropriate barriers on enrolled beneficiaries by denying or limiting access to treatments and interventions in ways that run counter to Medicare’s coverage policies.
According to Representative Diana DeGette (D-Colo.), who chaired a hearing on MA plans on June 28 by the House of Representatives’ Energy and Commerce Subcommittee on Oversight and Investigations, beneficiaries who are covered through an MA plan “do not always get the care that they are entitled to.”
The study by Dr. Essien and colleagues also documents some positives of care delivered through MA plans for patients with type 2 diabetes, compared with what FFS Medicare beneficiaries generally receive, such as significantly higher rates of screening for nephropathy and ophthalmologic disorders, and foot examinations.
But the apparently dampened use of SGLT2 inhibitors and GLP-1 receptor agonists among MA beneficiaries stand out as notable shortcomings, Dr. Essien maintained.
Cost containment may limit use
“The differences in health outcomes and in treatments in MA plans are important to highlight,” Dr. Essien said in an interview. “We worry that the cost-containment challenges [associated with MA plans] may be limiting use of these newer treatments.”
The study was based on 2014-2019 data from the Diabetes Collaborative Registry, which collects information from more than 5,000 U.S. clinicians whose practices include patients with diabetes, as well as claims data recorded by the Centers for Medicare and Medicaid Services during 2014-2017.
The main analysis focused on 345,911 Medicare beneficiaries with diabetes, which included 34% with MA coverage and 66% with FFS coverage. The two subgroups had similar ages, about 75 years old, and roughly half were women in both subgroups. The rate at which both subgroups received statin treatment was nearly the same: 72% for those with MA coverage and 71% for those with FFS Medicare.
But MA beneficiaries differed from those with FFS coverage in several other ways. MA beneficiaries had a higher prevalence of Medicaid eligibility than the FFS group (20% vs 12%) and lower rates of consultations with cardiologists (41% vs. 45%) or endocrinologists (7% vs. 10%).
Some of the positive differences in the care received by MA beneficiaries, compared with FFS beneficiaries, after adjustment for potential clinical and sociodemographic confounders, included:
- Screening for nephropathy, at a significant 14% higher relative rate.
- Screening for ophthalmologic disorders, at a significant 8% higher relative rate.
- Undergoing a diabetic foot examination, at a significant 13% higher relative rate.
- Receiving smoking-cessation counseling, at a significant 5% higher relative rate.
- Receiving treatment with an ACE inhibitor or angiotensin-receptor blocker (87% vs. 81%).
- More consistently receiving treatment with metformin, with rates of 72% versus 69% in 2017.
However, these positive differences were accompanied by these relative shortcomings for those with MA, compared with FFS coverage:
- Lower rates of treatment with an SGLT2 inhibitor (5.4% vs. 6.7%), a significant 9% relative difference after adjustment.
- Lower rates of treatment with a GLP-1 agonist (6.9% vs. 9.0%), a significant 20% relative difference after adjustment.
- Higher average levels of LDL cholesterol (81.5 vs. 78.9 mg/dL), a significantly higher average hemoglobin A1c level (7.1% vs. 7.0%), and a trend toward a lower prevalence of blood pressure control (70.3% vs. 71.5%).
Researchers also highlight that the lower rate at which people with MA coverage received SGLT2 inhibitors or GLP-1 agonists was consistent in patients with established cardiovascular or kidney disease, for whom these agents are particularly recommended.
In addition, a secondary analysis of data for another 65,000 Medicare beneficiaries in 2018 and 2019 showed the disparity in use of agents from these two drug classes continued.
Low systemic use of SGLT2 inhibitors, GLP-1 agonists
Dr. Essien acknowledged that, even in people with FFS Medicare coverage, use of SGLT2 inhibitors and GLP-1 agonists was low, but the difference between those with MA coverage is “important.”
Researchers offered four factors that might drive reduced prescribing of agents from these two classes for patients with type 2 diabetes with MA coverage: cost-containment strategies put in place by MA plans; the lower rate of consultations with specialists (cardiologists and endocrinologists); possible exclusion of clinicians from MA provider networks who tend to prescribe these higher-price agents; and lower household incomes of people with MA plans, which may lead to cost-related nonadherence.
Most SGLT2 inhibitors have an average retail cost of about $6,000/year, and some GLP-1 agonists cost more than $10,000/year.
In general, MA coverage includes more oversight of care and its cost than occurs with FFS coverage, noted Dr. Essien, an internal medicine physician at the University of Pittsburgh and a researcher at the Center for Health Equity Research and Promotion of the VA Pittsburgh Healthcare System.
“Incentives for using these more expensive treatments may not be there in MA plans,” he explained. Overcoming cost-related barriers is a challenge that will require “bold policy changes,” as well as better education of clinicians so they make correct treatment decisions, and of patients to resolve possible concerns about treatment safety.
Rep. DeGette hinted during her remarks at the June hearing that policy changes may be coming from Congress.
“Our seniors and their doctors should not be required to jump through numerous hoops to get coverage for straightforward and medically necessary procedures,” she said.
The study received no commercial funding. Dr. Essien reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
U.S. Medicare beneficiaries with type 2 diabetes who had health coverage through a Medicare Advantage (MA) plan received treatment with an sodium-glucose cotransporter 2 inhibitor or glucagonlike peptide–1 receptor agonist significantly less often than patients with traditional fee-for-service (FFS) Medicare coverage in 2014-2019, according to a study of more than 411,000 patients.
concluded Utibe R. Essien, MD, and coauthors in a study published in Diabetes Care.
The report comes as the U.S. Congress is looking closely at the MA program and evidence that insurance companies that provide these policies sometimes impose inappropriate barriers on enrolled beneficiaries by denying or limiting access to treatments and interventions in ways that run counter to Medicare’s coverage policies.
According to Representative Diana DeGette (D-Colo.), who chaired a hearing on MA plans on June 28 by the House of Representatives’ Energy and Commerce Subcommittee on Oversight and Investigations, beneficiaries who are covered through an MA plan “do not always get the care that they are entitled to.”
The study by Dr. Essien and colleagues also documents some positives of care delivered through MA plans for patients with type 2 diabetes, compared with what FFS Medicare beneficiaries generally receive, such as significantly higher rates of screening for nephropathy and ophthalmologic disorders, and foot examinations.
But the apparently dampened use of SGLT2 inhibitors and GLP-1 receptor agonists among MA beneficiaries stand out as notable shortcomings, Dr. Essien maintained.
Cost containment may limit use
“The differences in health outcomes and in treatments in MA plans are important to highlight,” Dr. Essien said in an interview. “We worry that the cost-containment challenges [associated with MA plans] may be limiting use of these newer treatments.”
The study was based on 2014-2019 data from the Diabetes Collaborative Registry, which collects information from more than 5,000 U.S. clinicians whose practices include patients with diabetes, as well as claims data recorded by the Centers for Medicare and Medicaid Services during 2014-2017.
The main analysis focused on 345,911 Medicare beneficiaries with diabetes, which included 34% with MA coverage and 66% with FFS coverage. The two subgroups had similar ages, about 75 years old, and roughly half were women in both subgroups. The rate at which both subgroups received statin treatment was nearly the same: 72% for those with MA coverage and 71% for those with FFS Medicare.
But MA beneficiaries differed from those with FFS coverage in several other ways. MA beneficiaries had a higher prevalence of Medicaid eligibility than the FFS group (20% vs 12%) and lower rates of consultations with cardiologists (41% vs. 45%) or endocrinologists (7% vs. 10%).
Some of the positive differences in the care received by MA beneficiaries, compared with FFS beneficiaries, after adjustment for potential clinical and sociodemographic confounders, included:
- Screening for nephropathy, at a significant 14% higher relative rate.
- Screening for ophthalmologic disorders, at a significant 8% higher relative rate.
- Undergoing a diabetic foot examination, at a significant 13% higher relative rate.
- Receiving smoking-cessation counseling, at a significant 5% higher relative rate.
- Receiving treatment with an ACE inhibitor or angiotensin-receptor blocker (87% vs. 81%).
- More consistently receiving treatment with metformin, with rates of 72% versus 69% in 2017.
However, these positive differences were accompanied by these relative shortcomings for those with MA, compared with FFS coverage:
- Lower rates of treatment with an SGLT2 inhibitor (5.4% vs. 6.7%), a significant 9% relative difference after adjustment.
- Lower rates of treatment with a GLP-1 agonist (6.9% vs. 9.0%), a significant 20% relative difference after adjustment.
- Higher average levels of LDL cholesterol (81.5 vs. 78.9 mg/dL), a significantly higher average hemoglobin A1c level (7.1% vs. 7.0%), and a trend toward a lower prevalence of blood pressure control (70.3% vs. 71.5%).
Researchers also highlight that the lower rate at which people with MA coverage received SGLT2 inhibitors or GLP-1 agonists was consistent in patients with established cardiovascular or kidney disease, for whom these agents are particularly recommended.
In addition, a secondary analysis of data for another 65,000 Medicare beneficiaries in 2018 and 2019 showed the disparity in use of agents from these two drug classes continued.
Low systemic use of SGLT2 inhibitors, GLP-1 agonists
Dr. Essien acknowledged that, even in people with FFS Medicare coverage, use of SGLT2 inhibitors and GLP-1 agonists was low, but the difference between those with MA coverage is “important.”
Researchers offered four factors that might drive reduced prescribing of agents from these two classes for patients with type 2 diabetes with MA coverage: cost-containment strategies put in place by MA plans; the lower rate of consultations with specialists (cardiologists and endocrinologists); possible exclusion of clinicians from MA provider networks who tend to prescribe these higher-price agents; and lower household incomes of people with MA plans, which may lead to cost-related nonadherence.
Most SGLT2 inhibitors have an average retail cost of about $6,000/year, and some GLP-1 agonists cost more than $10,000/year.
In general, MA coverage includes more oversight of care and its cost than occurs with FFS coverage, noted Dr. Essien, an internal medicine physician at the University of Pittsburgh and a researcher at the Center for Health Equity Research and Promotion of the VA Pittsburgh Healthcare System.
“Incentives for using these more expensive treatments may not be there in MA plans,” he explained. Overcoming cost-related barriers is a challenge that will require “bold policy changes,” as well as better education of clinicians so they make correct treatment decisions, and of patients to resolve possible concerns about treatment safety.
Rep. DeGette hinted during her remarks at the June hearing that policy changes may be coming from Congress.
“Our seniors and their doctors should not be required to jump through numerous hoops to get coverage for straightforward and medically necessary procedures,” she said.
The study received no commercial funding. Dr. Essien reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM DIABETES CARE
Fourth patient cleared of HIV after stem cell transplant for blood cancer
MONTREAL – from a naturally HIV-resistant donor, U.S. researchers announced at a meeting of the International AIDS Society.
The man received the transplant nearly 3.5 years ago. Since discontinuation of antiretroviral therapy (ART) more than 17 months ago, he has shown no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA, reported lead investigator Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope, a Duarte, Calif.–based stem cell transplantation center for patients with blood cancers and patients with HIV/blood cancer.
Known as the City of Hope (COH) patient, he is different from the three previously reported patients in that “he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions,” Dr. Dickter said during a press briefing for the meeting. “He has been living with HIV the longest of any of the patients to date – more than 31 years prior to transplant – and he had also received the least immunosuppressive preparative regimen prior to transplant,” she added.
She said that, like the three previous patients, known as the Berlin, London, and New York patients, the COH patient received a transplant from a donor with natural resistance to HIV because of a rare CCR5-delta 32 mutation.
Dr. Dickter and her coinvestigators used the term “remission” but went further, suggesting that an “HIV cure is feasible” after transplant, given this and the previous cases.
“It’s a bit early to say the patient is cured, but they are clearly in remission,” said Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the meeting. Nevertheless, Dr. Lewin, professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity, in Melbourne, acknowledged that cure is “very likely.”
“Two of the previously reported patients have been off ART for long periods of time – Berlin, 12 years (until Timothy’s death in 2020); London, 4 years – and both had far more extensive investigations to try and find intact virus, including very large blood draws, tissue biopsies, etc. For the New York and now this COH patient, the duration off ART has been much shorter. ... But given the prior cases, it is very likely that the New York and COH patients are indeed cured. But I think it’s too early to make that call, hence my preference to use the word, ‘remission,’ “ she told this news organization.
“Although a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” she added.
Dr. Dickter acknowledged that the complexity of stem cell transplant procedures and their potential for significant side effects make them unsuitable as treatment options for most people with HIV, although she said the COH case is evidence that some HIV patients with blood cancers may not need such intensive pretransplant conditioning regimens.
The COH patient received a reduced-intensity fludarabine and melphalan regimen that had been designed at Dr. Dickter’s center “for older and less fit patients to make transplantation more tolerable,” she said. In addition, the graft-vs.-host disease prophylaxis that the COH patient received included only tacrolimus and sirolimus, whereas the previous patients received additional immunosuppressive therapies, and some also had undergone total body irradiation.
Dr. Dickter has disclosed no relevant financial relationships. Dr. Lewin has relationships with AbbVie, BMS, Esfam, Genentech, Gilead, Immunocore, Merck, Vaxxinity, and Viiv.
A version of this article first appeared on Medscape.com.
MONTREAL – from a naturally HIV-resistant donor, U.S. researchers announced at a meeting of the International AIDS Society.
The man received the transplant nearly 3.5 years ago. Since discontinuation of antiretroviral therapy (ART) more than 17 months ago, he has shown no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA, reported lead investigator Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope, a Duarte, Calif.–based stem cell transplantation center for patients with blood cancers and patients with HIV/blood cancer.
Known as the City of Hope (COH) patient, he is different from the three previously reported patients in that “he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions,” Dr. Dickter said during a press briefing for the meeting. “He has been living with HIV the longest of any of the patients to date – more than 31 years prior to transplant – and he had also received the least immunosuppressive preparative regimen prior to transplant,” she added.
She said that, like the three previous patients, known as the Berlin, London, and New York patients, the COH patient received a transplant from a donor with natural resistance to HIV because of a rare CCR5-delta 32 mutation.
Dr. Dickter and her coinvestigators used the term “remission” but went further, suggesting that an “HIV cure is feasible” after transplant, given this and the previous cases.
“It’s a bit early to say the patient is cured, but they are clearly in remission,” said Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the meeting. Nevertheless, Dr. Lewin, professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity, in Melbourne, acknowledged that cure is “very likely.”
“Two of the previously reported patients have been off ART for long periods of time – Berlin, 12 years (until Timothy’s death in 2020); London, 4 years – and both had far more extensive investigations to try and find intact virus, including very large blood draws, tissue biopsies, etc. For the New York and now this COH patient, the duration off ART has been much shorter. ... But given the prior cases, it is very likely that the New York and COH patients are indeed cured. But I think it’s too early to make that call, hence my preference to use the word, ‘remission,’ “ she told this news organization.
“Although a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” she added.
Dr. Dickter acknowledged that the complexity of stem cell transplant procedures and their potential for significant side effects make them unsuitable as treatment options for most people with HIV, although she said the COH case is evidence that some HIV patients with blood cancers may not need such intensive pretransplant conditioning regimens.
The COH patient received a reduced-intensity fludarabine and melphalan regimen that had been designed at Dr. Dickter’s center “for older and less fit patients to make transplantation more tolerable,” she said. In addition, the graft-vs.-host disease prophylaxis that the COH patient received included only tacrolimus and sirolimus, whereas the previous patients received additional immunosuppressive therapies, and some also had undergone total body irradiation.
Dr. Dickter has disclosed no relevant financial relationships. Dr. Lewin has relationships with AbbVie, BMS, Esfam, Genentech, Gilead, Immunocore, Merck, Vaxxinity, and Viiv.
A version of this article first appeared on Medscape.com.
MONTREAL – from a naturally HIV-resistant donor, U.S. researchers announced at a meeting of the International AIDS Society.
The man received the transplant nearly 3.5 years ago. Since discontinuation of antiretroviral therapy (ART) more than 17 months ago, he has shown no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA, reported lead investigator Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope, a Duarte, Calif.–based stem cell transplantation center for patients with blood cancers and patients with HIV/blood cancer.
Known as the City of Hope (COH) patient, he is different from the three previously reported patients in that “he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions,” Dr. Dickter said during a press briefing for the meeting. “He has been living with HIV the longest of any of the patients to date – more than 31 years prior to transplant – and he had also received the least immunosuppressive preparative regimen prior to transplant,” she added.
She said that, like the three previous patients, known as the Berlin, London, and New York patients, the COH patient received a transplant from a donor with natural resistance to HIV because of a rare CCR5-delta 32 mutation.
Dr. Dickter and her coinvestigators used the term “remission” but went further, suggesting that an “HIV cure is feasible” after transplant, given this and the previous cases.
“It’s a bit early to say the patient is cured, but they are clearly in remission,” said Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the meeting. Nevertheless, Dr. Lewin, professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity, in Melbourne, acknowledged that cure is “very likely.”
“Two of the previously reported patients have been off ART for long periods of time – Berlin, 12 years (until Timothy’s death in 2020); London, 4 years – and both had far more extensive investigations to try and find intact virus, including very large blood draws, tissue biopsies, etc. For the New York and now this COH patient, the duration off ART has been much shorter. ... But given the prior cases, it is very likely that the New York and COH patients are indeed cured. But I think it’s too early to make that call, hence my preference to use the word, ‘remission,’ “ she told this news organization.
“Although a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” she added.
Dr. Dickter acknowledged that the complexity of stem cell transplant procedures and their potential for significant side effects make them unsuitable as treatment options for most people with HIV, although she said the COH case is evidence that some HIV patients with blood cancers may not need such intensive pretransplant conditioning regimens.
The COH patient received a reduced-intensity fludarabine and melphalan regimen that had been designed at Dr. Dickter’s center “for older and less fit patients to make transplantation more tolerable,” she said. In addition, the graft-vs.-host disease prophylaxis that the COH patient received included only tacrolimus and sirolimus, whereas the previous patients received additional immunosuppressive therapies, and some also had undergone total body irradiation.
Dr. Dickter has disclosed no relevant financial relationships. Dr. Lewin has relationships with AbbVie, BMS, Esfam, Genentech, Gilead, Immunocore, Merck, Vaxxinity, and Viiv.
A version of this article first appeared on Medscape.com.
AT AIDS 2022
Calcinosis Cutis Associated With Subcutaneous Glatiramer Acetate
To the Editor:
Calcinosis cutis is a condition characterized by the deposition of insoluble calcium salts in the skin. Dystrophic calcinosis cutis is the most common type, occurring in previously traumatized skin in the absence of abnormal blood calcium levels. It commonly is seen in patients with connective tissue diseases and is thought to be precipitated by chronic inflammation and vascular hypoxia.1 Herein, we describe a case of calcinosis cutis arising after treatment with subcutaneous glatiramer acetate, an agent that is effective for the treatment of relapsing-remitting multiple sclerosis (MS). Diagnostic workup and treatment modalities for calcinosis cutis in this patient population should be considered in the context of minimizing interruption or discontinuation of this disease-modifying agent.
A 53-year-old woman with a history of relapsing-remitting MS and systemic lupus erythematosus (SLE) presented with multiple firm asymptomatic subcutaneous nodules on the thighs of 1 year’s duration that were increasing in number. The involved areas were the injection sites of subcutaneous glatiramer acetate, an immunomodulator for the treatment of MS, which our patient self-administered 3 times weekly. Physical examination revealed multiple flesh-colored to white, firm, and nontender nodules on the thighs (Figure). There was no epidermal change, and she had no other skin involvement. A punch biopsy of one of the nodules revealed calcium deposits in collagen bundles of the deep dermis. Calcium, phosphorus, parathyroid hormone, and vitamin D levels were within reference range. She declined further treatment for the calcinosis cutis and opted to continue treatment with glatiramer acetate, as her MS was well controlled on this medication.
Glatiramer acetate is an immunogenic polypeptide injectable that is approved by the US Food and Drug Administration for the treatment of relapsing-remitting MS.2 It is composed of synthetic polypeptides and contains 4 naturally occurring amino acids. Glatiramer acetate is administered subcutaneously as 20 mg/mL/d or 40 mg/mL 3 times weekly. Transient injection-site reactions are the most common cutaneous adverse events and include localized edema, induration, erythema, pain, and pruritus.3 There have been multiple reports of lobular panniculitis and skin necrosis as well as embolia cutis medicamentosa (Nicolau syndrome).4,5 Our case of calcinosis cutis related to glatiramer acetate is unique. The mechanism of calcinosis cutis in our patient likely was dystrophic due to tissue damage, rather than due to the injection of a calcium-containing substance. Our patient’s history of SLE is a notable risk factor for the development of calcinosis cutis, likely incited by the trauma occurring with subcutaneous injections.6
The mainstay of treatment for localized calcinosis cutis in the setting of connective tissue disease is surgical excision as well as treatment of the underlying disorder. Potential therapies include calcium channel blockers, warfarin, bisphosphonates, intravenous immunoglobulin, minocycline, colchicine, anti–tumor necrosis factor agents, intralesional corticosteroids, intravenous sodium thiosulfate, and CO2 laser.1,6 Our patient was already on intravenous immunoglobulin for MS and hydroxychloroquine for SLE. In select cases where the patient is asymptomatic and prefers not to pursue treatment, no treatment is necessary.
Although calcinosis cutis may occur in SLE alone, it is uncommon and usually is seen in chronic severe SLE, where calcification usually occurs in the setting of pre-existing cutaneous lupus.4 This case report of calcinosis cutis following treatment with glatiramer acetate highlights some of the cutaneous side effects associated with glatiramer acetate injections and should prompt practitioners to consider dystrophic calcinosis cutis in patients requiring subcutaneous medications, particularly in those with pre-existing connective tissue disease.
- Valenzuela A, Chung L. Calcinosis: pathophysiology and management. Curr Opin Rheumatol. 2015;27:542-548.
- Copaxone. Prescribing information. Teva Neuroscience, Inc; 2022. Accessed July 15, 2022. https://www.copaxone.com/globalassets/copaxone/prescribing-information.pdf
- McKeage K. Glatiramer acetate 40 mg/mL in relapsing-remitting multiple sclerosis: a review. CNS Drugs. 2015;29:425-432.
- Balak DMW, Hengstman GJD, Çakmak A, et al. Cutaneous adverse events associated with disease-modifying treatment in multiple sclerosis: a systematic review. Mult Scler. 2012;18:1705-1717.
- Watkins CE, Litchfield J, Youngberg G, et al. Glatiramer acetate-induced lobular panniculitis and skin necrosis. Cutis. 2015;95:E26-E30.
- Reiter N, El-Shabrawi L, Leinweber B, et al. Calcinosis cutis. J Am Acad Dermatol. 2011;65:1-12.
To the Editor:
Calcinosis cutis is a condition characterized by the deposition of insoluble calcium salts in the skin. Dystrophic calcinosis cutis is the most common type, occurring in previously traumatized skin in the absence of abnormal blood calcium levels. It commonly is seen in patients with connective tissue diseases and is thought to be precipitated by chronic inflammation and vascular hypoxia.1 Herein, we describe a case of calcinosis cutis arising after treatment with subcutaneous glatiramer acetate, an agent that is effective for the treatment of relapsing-remitting multiple sclerosis (MS). Diagnostic workup and treatment modalities for calcinosis cutis in this patient population should be considered in the context of minimizing interruption or discontinuation of this disease-modifying agent.
A 53-year-old woman with a history of relapsing-remitting MS and systemic lupus erythematosus (SLE) presented with multiple firm asymptomatic subcutaneous nodules on the thighs of 1 year’s duration that were increasing in number. The involved areas were the injection sites of subcutaneous glatiramer acetate, an immunomodulator for the treatment of MS, which our patient self-administered 3 times weekly. Physical examination revealed multiple flesh-colored to white, firm, and nontender nodules on the thighs (Figure). There was no epidermal change, and she had no other skin involvement. A punch biopsy of one of the nodules revealed calcium deposits in collagen bundles of the deep dermis. Calcium, phosphorus, parathyroid hormone, and vitamin D levels were within reference range. She declined further treatment for the calcinosis cutis and opted to continue treatment with glatiramer acetate, as her MS was well controlled on this medication.
Glatiramer acetate is an immunogenic polypeptide injectable that is approved by the US Food and Drug Administration for the treatment of relapsing-remitting MS.2 It is composed of synthetic polypeptides and contains 4 naturally occurring amino acids. Glatiramer acetate is administered subcutaneously as 20 mg/mL/d or 40 mg/mL 3 times weekly. Transient injection-site reactions are the most common cutaneous adverse events and include localized edema, induration, erythema, pain, and pruritus.3 There have been multiple reports of lobular panniculitis and skin necrosis as well as embolia cutis medicamentosa (Nicolau syndrome).4,5 Our case of calcinosis cutis related to glatiramer acetate is unique. The mechanism of calcinosis cutis in our patient likely was dystrophic due to tissue damage, rather than due to the injection of a calcium-containing substance. Our patient’s history of SLE is a notable risk factor for the development of calcinosis cutis, likely incited by the trauma occurring with subcutaneous injections.6
The mainstay of treatment for localized calcinosis cutis in the setting of connective tissue disease is surgical excision as well as treatment of the underlying disorder. Potential therapies include calcium channel blockers, warfarin, bisphosphonates, intravenous immunoglobulin, minocycline, colchicine, anti–tumor necrosis factor agents, intralesional corticosteroids, intravenous sodium thiosulfate, and CO2 laser.1,6 Our patient was already on intravenous immunoglobulin for MS and hydroxychloroquine for SLE. In select cases where the patient is asymptomatic and prefers not to pursue treatment, no treatment is necessary.
Although calcinosis cutis may occur in SLE alone, it is uncommon and usually is seen in chronic severe SLE, where calcification usually occurs in the setting of pre-existing cutaneous lupus.4 This case report of calcinosis cutis following treatment with glatiramer acetate highlights some of the cutaneous side effects associated with glatiramer acetate injections and should prompt practitioners to consider dystrophic calcinosis cutis in patients requiring subcutaneous medications, particularly in those with pre-existing connective tissue disease.
To the Editor:
Calcinosis cutis is a condition characterized by the deposition of insoluble calcium salts in the skin. Dystrophic calcinosis cutis is the most common type, occurring in previously traumatized skin in the absence of abnormal blood calcium levels. It commonly is seen in patients with connective tissue diseases and is thought to be precipitated by chronic inflammation and vascular hypoxia.1 Herein, we describe a case of calcinosis cutis arising after treatment with subcutaneous glatiramer acetate, an agent that is effective for the treatment of relapsing-remitting multiple sclerosis (MS). Diagnostic workup and treatment modalities for calcinosis cutis in this patient population should be considered in the context of minimizing interruption or discontinuation of this disease-modifying agent.
A 53-year-old woman with a history of relapsing-remitting MS and systemic lupus erythematosus (SLE) presented with multiple firm asymptomatic subcutaneous nodules on the thighs of 1 year’s duration that were increasing in number. The involved areas were the injection sites of subcutaneous glatiramer acetate, an immunomodulator for the treatment of MS, which our patient self-administered 3 times weekly. Physical examination revealed multiple flesh-colored to white, firm, and nontender nodules on the thighs (Figure). There was no epidermal change, and she had no other skin involvement. A punch biopsy of one of the nodules revealed calcium deposits in collagen bundles of the deep dermis. Calcium, phosphorus, parathyroid hormone, and vitamin D levels were within reference range. She declined further treatment for the calcinosis cutis and opted to continue treatment with glatiramer acetate, as her MS was well controlled on this medication.
Glatiramer acetate is an immunogenic polypeptide injectable that is approved by the US Food and Drug Administration for the treatment of relapsing-remitting MS.2 It is composed of synthetic polypeptides and contains 4 naturally occurring amino acids. Glatiramer acetate is administered subcutaneously as 20 mg/mL/d or 40 mg/mL 3 times weekly. Transient injection-site reactions are the most common cutaneous adverse events and include localized edema, induration, erythema, pain, and pruritus.3 There have been multiple reports of lobular panniculitis and skin necrosis as well as embolia cutis medicamentosa (Nicolau syndrome).4,5 Our case of calcinosis cutis related to glatiramer acetate is unique. The mechanism of calcinosis cutis in our patient likely was dystrophic due to tissue damage, rather than due to the injection of a calcium-containing substance. Our patient’s history of SLE is a notable risk factor for the development of calcinosis cutis, likely incited by the trauma occurring with subcutaneous injections.6
The mainstay of treatment for localized calcinosis cutis in the setting of connective tissue disease is surgical excision as well as treatment of the underlying disorder. Potential therapies include calcium channel blockers, warfarin, bisphosphonates, intravenous immunoglobulin, minocycline, colchicine, anti–tumor necrosis factor agents, intralesional corticosteroids, intravenous sodium thiosulfate, and CO2 laser.1,6 Our patient was already on intravenous immunoglobulin for MS and hydroxychloroquine for SLE. In select cases where the patient is asymptomatic and prefers not to pursue treatment, no treatment is necessary.
Although calcinosis cutis may occur in SLE alone, it is uncommon and usually is seen in chronic severe SLE, where calcification usually occurs in the setting of pre-existing cutaneous lupus.4 This case report of calcinosis cutis following treatment with glatiramer acetate highlights some of the cutaneous side effects associated with glatiramer acetate injections and should prompt practitioners to consider dystrophic calcinosis cutis in patients requiring subcutaneous medications, particularly in those with pre-existing connective tissue disease.
- Valenzuela A, Chung L. Calcinosis: pathophysiology and management. Curr Opin Rheumatol. 2015;27:542-548.
- Copaxone. Prescribing information. Teva Neuroscience, Inc; 2022. Accessed July 15, 2022. https://www.copaxone.com/globalassets/copaxone/prescribing-information.pdf
- McKeage K. Glatiramer acetate 40 mg/mL in relapsing-remitting multiple sclerosis: a review. CNS Drugs. 2015;29:425-432.
- Balak DMW, Hengstman GJD, Çakmak A, et al. Cutaneous adverse events associated with disease-modifying treatment in multiple sclerosis: a systematic review. Mult Scler. 2012;18:1705-1717.
- Watkins CE, Litchfield J, Youngberg G, et al. Glatiramer acetate-induced lobular panniculitis and skin necrosis. Cutis. 2015;95:E26-E30.
- Reiter N, El-Shabrawi L, Leinweber B, et al. Calcinosis cutis. J Am Acad Dermatol. 2011;65:1-12.
- Valenzuela A, Chung L. Calcinosis: pathophysiology and management. Curr Opin Rheumatol. 2015;27:542-548.
- Copaxone. Prescribing information. Teva Neuroscience, Inc; 2022. Accessed July 15, 2022. https://www.copaxone.com/globalassets/copaxone/prescribing-information.pdf
- McKeage K. Glatiramer acetate 40 mg/mL in relapsing-remitting multiple sclerosis: a review. CNS Drugs. 2015;29:425-432.
- Balak DMW, Hengstman GJD, Çakmak A, et al. Cutaneous adverse events associated with disease-modifying treatment in multiple sclerosis: a systematic review. Mult Scler. 2012;18:1705-1717.
- Watkins CE, Litchfield J, Youngberg G, et al. Glatiramer acetate-induced lobular panniculitis and skin necrosis. Cutis. 2015;95:E26-E30.
- Reiter N, El-Shabrawi L, Leinweber B, et al. Calcinosis cutis. J Am Acad Dermatol. 2011;65:1-12.
Practice Points
- Glatiramer acetate is a subcutaneous injection utilized for relapsing-remitting multiple sclerosis, and common adverse effects include injection-site reactions such as calcinosis cutis.
- Development of calcinosis cutis in association with glatiramer acetate is not an indication for medication discontinuation.
- Dermatologists should be aware of this potential association, and treatment should be considered in cases of symptomatic calcinosis cutis.
