Dermatology News

A new review of the literature on climate change and atopic dermatitis (AD) found evidence of a broad and negative impact of climatic hazards on various aspects of AD, including prevalence, severity/flares, and AD-related health care utilization. But it also showed the extent to which research is lacking.

“There’s not as much out there as one might expect, given that this is the most common dermatologic disease and one of the most burdensome diseases worldwide,” said Katrina Abuabara, MD, of the department of dermatology at the University of California, San Francisco, one of the senior authors of the review.

Dr. Abuabara

“There’s a genetic predisposition to AD, but it’s certainly very environmentally patterned,” she said in an interview. “Given that we know there are strong environmental influences, it’s an obvious example of how climate change affects our health ... It is one that may be underappreciated and that could give us near-term information.”

Indeed, she and her coauthors emphasized in their paper, “AD could serve as a case study for climatic impacts on health.” The review, which looked beyond the realm of air pollution, was published in Allergy, the journal of the European Academy of Allergy and Clinical Immunology. 

Dr. Abuabara, UCSF dermatologist Sheng-Pei Wang, MD, MPH, and their coauthors — dermatologists and others from the United States, Europe, Brazil, and India — were convened by the International Eczema Council and teamed up with a biologist and climate science expert, Camilo Mora, PhD, of the University of Hawaii at Mānoa, Honolulu. Because research to date has focused on air pollution, with the impact of other hazards that Dr. Abuabara said were “a lot less developed and organized,” they used a framework and search strategy developed by Dr. Mora that looks at 10 climatic hazards related to greenhouse gas emissions, including heat waves, drought, precipitation, wildfires, and sea level rise.

“Given that this [framework] was already out there in the literature, we thought it would give us a structure and a nice way to organize the literature,” Dr. Abuabara said. While the literature is too heterogeneous for a systematic review and meta-analysis, the researchers used a systematic approach, she explained.

Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and a coauthor of the paper, said in an e-mail that the review raises “our consciousness about how these [climate] changes may be impacting atopic dermatitis.”

Courtesy University of California, San Diego

Mixed Results, But Negative Impacts Overall

The researchers identified 18 studies across most of the 10 climatic hazards with evidence for an impact on AD, the majority of which demonstrated harmful effects on various aspects of AD — most commonly on AD-related health care utilization and severity/flares. Only three of the studies examined AD prevalence and notably, none looked at incidence.

angkhan/Getty Images

The impact of climatic hazards on AD appears to vary depending on the geographic region and its baseline climate, the authors said. A study in South Korea, for instance, found that in areas declared as disaster zones after storms and heavy rains, the number of AD-related outpatient visits increased for all ages. And a study in the United States showed an increased prevalence of childhood eczema in states with higher mean annual precipitation. However, some other studies on precipitation found no associations.

Just as published studies on precipitation yielded mixed results, so have studies on warming temperatures, Dr. Abuabara and her colleagues reported in their paper, with higher temperatures found to be positively associated with severity of AD symptoms in a study among patients with AD living in a region of Southern Italy, but decreased AD-related health care utilization in a study in Denmark.

In another study of over 5,500 children enrolled in an eczema registry in the United States between 2004 and 2012, higher temperature (odds ratio [OR] = 0.90, P < .001) and increased sun exposure (OR = 0.93, P = .009) were associated with poorly controlled eczema, after the researchers controlled for gender, race, income, and topical medication use.

Studies From 10 Countries Reviewed

Across the 18 studies identified in the review, data were collected in 10 countries. Five studies were conducted in the United States, one used global data, six were from Asia, and the others were from Europe and Africa. Data are lacking, the researchers wrote, in many parts of the world, including coastal regions of the tropics that are projected to experience the largest cumulative climatic hazards.

Future research should not only cover more geographic areas — especially those most impacted by climate change — but should examine impacts on AD incidence, prevalence, and “long-term monitoring of disease activity over time at the individual level,” the researchers recommended. Research should also aim to integrate multiple climatic factors and types of climate data, they said.

“As researchers, we always like to distill things down, but with climatic hazards like warming, you have to integrate other factors such as what the baseline temperature is and how precipitation is involved,” Dr. Abuabara said in the interview. With precipitation, similarly, associated factors such as outdoor humidity, pollen, and pollution exposure may also be at play for AD. Overall, she said, “you have to integrate many types of data.”

In addition to their literature review, the researchers created maps comparing the past, present, and future burden of climatic hazards to AD prevalence data. One pair of maps illustrates global cumulative exposure to climatic hazards in 2005 in parallel with the estimated annual change in AD prevalence in the subsequent decade. “It’s meant to be descriptive,” Dr. Abuabara said in the interview. The maps show alignment “between the areas experiencing the most climatic hazards and those where we subsequently saw the most rapid changes in AD.”

The paper also describes how climatic factors impact skin physiology and AD — exacerbating barrier impairment, immune dysregulation, dysbiosis, and pruritus — and how there are differential impacts on vulnerable and displaced populations with AD. It also briefly addresses air pollution, which was not included in the review framework but is impacted by wildfire and other included climatic factors.
 

The Need to Better Track AD, Anticipate Clinical Impact

“Outside of epidemiology, [clinicians and others] may not realize we actually have fairly poor measures of prevalence and severity of AD and disease flare over time,” Dr. Abuabara said. So “improving the ways we can measure this disease and getting more detailed data is important” for assessing the impact of climate changes.

More skin measures should be incorporated into large national health surveys, for one. “Skin doesn’t come to mind as much as diseases like heart disease and diabetes,” she said, and when surveys ask about AD, “they often don’t ask specific enough questions or ask about severity.” The clinical impacts of adverse climatic changes and extreme weather events — sudden therapy interruption, particularly of systemic agents, and delayed treatment, for instance — should be reflected in the planning and provision of dermatology services, Dr. Abuabara and her coauthors wrote.

There are currently no evidence-based recommendations for what patients with AD can do differently when faced with wildfire smoke or other climatic hazards, other than general recommendations, for instance, to reduce exposure to wildfire smoke and aeroallergens, she said in the interview. But “overall, the field has moved to more proactive treatment patterns ... toward providing anticipatory guidance and having individualized treatment plans that give people the tools to be ready to step things up or counteract [flares or worsening] if they need to.”

She and her San Francisco–based coauthors have already experienced the impact of wildfires firsthand. “It was amazing — in the period right after a major wildfire hundreds of miles away from the Bay area, we saw a huge spike in visits for itch and for eczema,” she said, referring to research on AD clinic visits after the 2018 California Camp Fire. “It showed up dramatically in the data,” said Dr. Abuabara, one of the authors of that study.

The new review adds to a growing body of literature documenting health impacts of climate change and advocating for action. In September 2021, more than 230 medical journals, including the New England Journal of Medicine — though not any dermatology journals — published an editorial calling for emergency action to limit global warming and protect health.

The following year, a commentary published across four dermatology journals discussed current and future impacts of climate change and urged dermatologists to become more engaged in finding solutions to help mitigate and adapt to climate change.

More recently, dermatologists have published about the environmental impact of professional practices such as print journals and meeting samples using single-use plastics.

Dr. Abuabara disclosed to Allergy that she is a consultant for TARGET RWE and Amgen and that her institution receives grants for research from Pfizer and LaRoche Posay. Dr. Eichenfield reported serving as a scientific adviser, consultant, and/or study investigator for Pfizer, AbbVie, Amgen and other companies. Dr. Wang disclosed that she is an International Eczema Council Fellow with financial support from Abbvie. Other authors had multiple disclosures.

A new review of the literature on climate change and atopic dermatitis (AD) found evidence of a broad and negative impact of climatic hazards on various aspects of AD, including prevalence, severity/flares, and AD-related health care utilization. But it also showed the extent to which research is lacking.

“There’s not as much out there as one might expect, given that this is the most common dermatologic disease and one of the most burdensome diseases worldwide,” said Katrina Abuabara, MD, of the department of dermatology at the University of California, San Francisco, one of the senior authors of the review.

Dr. Abuabara

“There’s a genetic predisposition to AD, but it’s certainly very environmentally patterned,” she said in an interview. “Given that we know there are strong environmental influences, it’s an obvious example of how climate change affects our health ... It is one that may be underappreciated and that could give us near-term information.”

Indeed, she and her coauthors emphasized in their paper, “AD could serve as a case study for climatic impacts on health.” The review, which looked beyond the realm of air pollution, was published in Allergy, the journal of the European Academy of Allergy and Clinical Immunology. 

Dr. Abuabara, UCSF dermatologist Sheng-Pei Wang, MD, MPH, and their coauthors — dermatologists and others from the United States, Europe, Brazil, and India — were convened by the International Eczema Council and teamed up with a biologist and climate science expert, Camilo Mora, PhD, of the University of Hawaii at Mānoa, Honolulu. Because research to date has focused on air pollution, with the impact of other hazards that Dr. Abuabara said were “a lot less developed and organized,” they used a framework and search strategy developed by Dr. Mora that looks at 10 climatic hazards related to greenhouse gas emissions, including heat waves, drought, precipitation, wildfires, and sea level rise.

“Given that this [framework] was already out there in the literature, we thought it would give us a structure and a nice way to organize the literature,” Dr. Abuabara said. While the literature is too heterogeneous for a systematic review and meta-analysis, the researchers used a systematic approach, she explained.

Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and a coauthor of the paper, said in an e-mail that the review raises “our consciousness about how these [climate] changes may be impacting atopic dermatitis.”

Courtesy University of California, San Diego

Mixed Results, But Negative Impacts Overall

The researchers identified 18 studies across most of the 10 climatic hazards with evidence for an impact on AD, the majority of which demonstrated harmful effects on various aspects of AD — most commonly on AD-related health care utilization and severity/flares. Only three of the studies examined AD prevalence and notably, none looked at incidence.

angkhan/Getty Images

The impact of climatic hazards on AD appears to vary depending on the geographic region and its baseline climate, the authors said. A study in South Korea, for instance, found that in areas declared as disaster zones after storms and heavy rains, the number of AD-related outpatient visits increased for all ages. And a study in the United States showed an increased prevalence of childhood eczema in states with higher mean annual precipitation. However, some other studies on precipitation found no associations.

Just as published studies on precipitation yielded mixed results, so have studies on warming temperatures, Dr. Abuabara and her colleagues reported in their paper, with higher temperatures found to be positively associated with severity of AD symptoms in a study among patients with AD living in a region of Southern Italy, but decreased AD-related health care utilization in a study in Denmark.

In another study of over 5,500 children enrolled in an eczema registry in the United States between 2004 and 2012, higher temperature (odds ratio [OR] = 0.90, P < .001) and increased sun exposure (OR = 0.93, P = .009) were associated with poorly controlled eczema, after the researchers controlled for gender, race, income, and topical medication use.

Studies From 10 Countries Reviewed

Across the 18 studies identified in the review, data were collected in 10 countries. Five studies were conducted in the United States, one used global data, six were from Asia, and the others were from Europe and Africa. Data are lacking, the researchers wrote, in many parts of the world, including coastal regions of the tropics that are projected to experience the largest cumulative climatic hazards.

Future research should not only cover more geographic areas — especially those most impacted by climate change — but should examine impacts on AD incidence, prevalence, and “long-term monitoring of disease activity over time at the individual level,” the researchers recommended. Research should also aim to integrate multiple climatic factors and types of climate data, they said.

“As researchers, we always like to distill things down, but with climatic hazards like warming, you have to integrate other factors such as what the baseline temperature is and how precipitation is involved,” Dr. Abuabara said in the interview. With precipitation, similarly, associated factors such as outdoor humidity, pollen, and pollution exposure may also be at play for AD. Overall, she said, “you have to integrate many types of data.”

In addition to their literature review, the researchers created maps comparing the past, present, and future burden of climatic hazards to AD prevalence data. One pair of maps illustrates global cumulative exposure to climatic hazards in 2005 in parallel with the estimated annual change in AD prevalence in the subsequent decade. “It’s meant to be descriptive,” Dr. Abuabara said in the interview. The maps show alignment “between the areas experiencing the most climatic hazards and those where we subsequently saw the most rapid changes in AD.”

The paper also describes how climatic factors impact skin physiology and AD — exacerbating barrier impairment, immune dysregulation, dysbiosis, and pruritus — and how there are differential impacts on vulnerable and displaced populations with AD. It also briefly addresses air pollution, which was not included in the review framework but is impacted by wildfire and other included climatic factors.
 

The Need to Better Track AD, Anticipate Clinical Impact

“Outside of epidemiology, [clinicians and others] may not realize we actually have fairly poor measures of prevalence and severity of AD and disease flare over time,” Dr. Abuabara said. So “improving the ways we can measure this disease and getting more detailed data is important” for assessing the impact of climate changes.

More skin measures should be incorporated into large national health surveys, for one. “Skin doesn’t come to mind as much as diseases like heart disease and diabetes,” she said, and when surveys ask about AD, “they often don’t ask specific enough questions or ask about severity.” The clinical impacts of adverse climatic changes and extreme weather events — sudden therapy interruption, particularly of systemic agents, and delayed treatment, for instance — should be reflected in the planning and provision of dermatology services, Dr. Abuabara and her coauthors wrote.

There are currently no evidence-based recommendations for what patients with AD can do differently when faced with wildfire smoke or other climatic hazards, other than general recommendations, for instance, to reduce exposure to wildfire smoke and aeroallergens, she said in the interview. But “overall, the field has moved to more proactive treatment patterns ... toward providing anticipatory guidance and having individualized treatment plans that give people the tools to be ready to step things up or counteract [flares or worsening] if they need to.”

She and her San Francisco–based coauthors have already experienced the impact of wildfires firsthand. “It was amazing — in the period right after a major wildfire hundreds of miles away from the Bay area, we saw a huge spike in visits for itch and for eczema,” she said, referring to research on AD clinic visits after the 2018 California Camp Fire. “It showed up dramatically in the data,” said Dr. Abuabara, one of the authors of that study.

The new review adds to a growing body of literature documenting health impacts of climate change and advocating for action. In September 2021, more than 230 medical journals, including the New England Journal of Medicine — though not any dermatology journals — published an editorial calling for emergency action to limit global warming and protect health.

The following year, a commentary published across four dermatology journals discussed current and future impacts of climate change and urged dermatologists to become more engaged in finding solutions to help mitigate and adapt to climate change.

More recently, dermatologists have published about the environmental impact of professional practices such as print journals and meeting samples using single-use plastics.

Dr. Abuabara disclosed to Allergy that she is a consultant for TARGET RWE and Amgen and that her institution receives grants for research from Pfizer and LaRoche Posay. Dr. Eichenfield reported serving as a scientific adviser, consultant, and/or study investigator for Pfizer, AbbVie, Amgen and other companies. Dr. Wang disclosed that she is an International Eczema Council Fellow with financial support from Abbvie. Other authors had multiple disclosures.

A new review of the literature on climate change and atopic dermatitis (AD) found evidence of a broad and negative impact of climatic hazards on various aspects of AD, including prevalence, severity/flares, and AD-related health care utilization. But it also showed the extent to which research is lacking.

“There’s not as much out there as one might expect, given that this is the most common dermatologic disease and one of the most burdensome diseases worldwide,” said Katrina Abuabara, MD, of the department of dermatology at the University of California, San Francisco, one of the senior authors of the review.

Dr. Abuabara

“There’s a genetic predisposition to AD, but it’s certainly very environmentally patterned,” she said in an interview. “Given that we know there are strong environmental influences, it’s an obvious example of how climate change affects our health ... It is one that may be underappreciated and that could give us near-term information.”

Indeed, she and her coauthors emphasized in their paper, “AD could serve as a case study for climatic impacts on health.” The review, which looked beyond the realm of air pollution, was published in Allergy, the journal of the European Academy of Allergy and Clinical Immunology. 

Dr. Abuabara, UCSF dermatologist Sheng-Pei Wang, MD, MPH, and their coauthors — dermatologists and others from the United States, Europe, Brazil, and India — were convened by the International Eczema Council and teamed up with a biologist and climate science expert, Camilo Mora, PhD, of the University of Hawaii at Mānoa, Honolulu. Because research to date has focused on air pollution, with the impact of other hazards that Dr. Abuabara said were “a lot less developed and organized,” they used a framework and search strategy developed by Dr. Mora that looks at 10 climatic hazards related to greenhouse gas emissions, including heat waves, drought, precipitation, wildfires, and sea level rise.

“Given that this [framework] was already out there in the literature, we thought it would give us a structure and a nice way to organize the literature,” Dr. Abuabara said. While the literature is too heterogeneous for a systematic review and meta-analysis, the researchers used a systematic approach, she explained.

Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and a coauthor of the paper, said in an e-mail that the review raises “our consciousness about how these [climate] changes may be impacting atopic dermatitis.”

Courtesy University of California, San Diego

Mixed Results, But Negative Impacts Overall

The researchers identified 18 studies across most of the 10 climatic hazards with evidence for an impact on AD, the majority of which demonstrated harmful effects on various aspects of AD — most commonly on AD-related health care utilization and severity/flares. Only three of the studies examined AD prevalence and notably, none looked at incidence.

angkhan/Getty Images

The impact of climatic hazards on AD appears to vary depending on the geographic region and its baseline climate, the authors said. A study in South Korea, for instance, found that in areas declared as disaster zones after storms and heavy rains, the number of AD-related outpatient visits increased for all ages. And a study in the United States showed an increased prevalence of childhood eczema in states with higher mean annual precipitation. However, some other studies on precipitation found no associations.

Just as published studies on precipitation yielded mixed results, so have studies on warming temperatures, Dr. Abuabara and her colleagues reported in their paper, with higher temperatures found to be positively associated with severity of AD symptoms in a study among patients with AD living in a region of Southern Italy, but decreased AD-related health care utilization in a study in Denmark.

In another study of over 5,500 children enrolled in an eczema registry in the United States between 2004 and 2012, higher temperature (odds ratio [OR] = 0.90, P < .001) and increased sun exposure (OR = 0.93, P = .009) were associated with poorly controlled eczema, after the researchers controlled for gender, race, income, and topical medication use.

Studies From 10 Countries Reviewed

Across the 18 studies identified in the review, data were collected in 10 countries. Five studies were conducted in the United States, one used global data, six were from Asia, and the others were from Europe and Africa. Data are lacking, the researchers wrote, in many parts of the world, including coastal regions of the tropics that are projected to experience the largest cumulative climatic hazards.

Future research should not only cover more geographic areas — especially those most impacted by climate change — but should examine impacts on AD incidence, prevalence, and “long-term monitoring of disease activity over time at the individual level,” the researchers recommended. Research should also aim to integrate multiple climatic factors and types of climate data, they said.

“As researchers, we always like to distill things down, but with climatic hazards like warming, you have to integrate other factors such as what the baseline temperature is and how precipitation is involved,” Dr. Abuabara said in the interview. With precipitation, similarly, associated factors such as outdoor humidity, pollen, and pollution exposure may also be at play for AD. Overall, she said, “you have to integrate many types of data.”

In addition to their literature review, the researchers created maps comparing the past, present, and future burden of climatic hazards to AD prevalence data. One pair of maps illustrates global cumulative exposure to climatic hazards in 2005 in parallel with the estimated annual change in AD prevalence in the subsequent decade. “It’s meant to be descriptive,” Dr. Abuabara said in the interview. The maps show alignment “between the areas experiencing the most climatic hazards and those where we subsequently saw the most rapid changes in AD.”

The paper also describes how climatic factors impact skin physiology and AD — exacerbating barrier impairment, immune dysregulation, dysbiosis, and pruritus — and how there are differential impacts on vulnerable and displaced populations with AD. It also briefly addresses air pollution, which was not included in the review framework but is impacted by wildfire and other included climatic factors.
 

The Need to Better Track AD, Anticipate Clinical Impact

“Outside of epidemiology, [clinicians and others] may not realize we actually have fairly poor measures of prevalence and severity of AD and disease flare over time,” Dr. Abuabara said. So “improving the ways we can measure this disease and getting more detailed data is important” for assessing the impact of climate changes.

More skin measures should be incorporated into large national health surveys, for one. “Skin doesn’t come to mind as much as diseases like heart disease and diabetes,” she said, and when surveys ask about AD, “they often don’t ask specific enough questions or ask about severity.” The clinical impacts of adverse climatic changes and extreme weather events — sudden therapy interruption, particularly of systemic agents, and delayed treatment, for instance — should be reflected in the planning and provision of dermatology services, Dr. Abuabara and her coauthors wrote.

There are currently no evidence-based recommendations for what patients with AD can do differently when faced with wildfire smoke or other climatic hazards, other than general recommendations, for instance, to reduce exposure to wildfire smoke and aeroallergens, she said in the interview. But “overall, the field has moved to more proactive treatment patterns ... toward providing anticipatory guidance and having individualized treatment plans that give people the tools to be ready to step things up or counteract [flares or worsening] if they need to.”

She and her San Francisco–based coauthors have already experienced the impact of wildfires firsthand. “It was amazing — in the period right after a major wildfire hundreds of miles away from the Bay area, we saw a huge spike in visits for itch and for eczema,” she said, referring to research on AD clinic visits after the 2018 California Camp Fire. “It showed up dramatically in the data,” said Dr. Abuabara, one of the authors of that study.

The new review adds to a growing body of literature documenting health impacts of climate change and advocating for action. In September 2021, more than 230 medical journals, including the New England Journal of Medicine — though not any dermatology journals — published an editorial calling for emergency action to limit global warming and protect health.

The following year, a commentary published across four dermatology journals discussed current and future impacts of climate change and urged dermatologists to become more engaged in finding solutions to help mitigate and adapt to climate change.

More recently, dermatologists have published about the environmental impact of professional practices such as print journals and meeting samples using single-use plastics.

Dr. Abuabara disclosed to Allergy that she is a consultant for TARGET RWE and Amgen and that her institution receives grants for research from Pfizer and LaRoche Posay. Dr. Eichenfield reported serving as a scientific adviser, consultant, and/or study investigator for Pfizer, AbbVie, Amgen and other companies. Dr. Wang disclosed that she is an International Eczema Council Fellow with financial support from Abbvie. Other authors had multiple disclosures.

The US Food and Drug Administration has approved the first interchangeable, high-concentration, citrate-free adalimumab biosimilar, adalimumab-ryvk (Simlandi).

This is the 10th adalimumab biosimilar approved by the regulatory agency and the first biosimilar approval in the US market for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals.

“An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the U.S.,” said Robert Wessman, chairman and CEO of Alvotech, in a company press release on February 23.

Adalimumab-ryvk was approved in the European Union in 2021 and in Australia and Canada in 2022. 

Adalimumab-ryvk is indicated for adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, plaque psoriasis, hidradenitis suppurativa, and noninfectious intermediate and posterior uveitis and panuveitis. In pediatric patients, it is indicated for polyarticular juvenile idiopathic arthritis in children 2 years of age and older and Crohn’s disease in children 6 years of age and older.

Adalimumab-ryvk is the third Humira biosimilar overall granted interchangeability status, which allows pharmacists (depending on state law) to substitute the biosimilar for the reference product without involving the prescribing clinician. Adalimumab-adbm (Cyltezo), manufactured by Boehringer Ingelheim, and adalimumab-afzb (Abrilada), manufactured by Pfizer, were previously granted interchangeability status; however, they both are interchangeable with the low-concentration formulation of Humira, which make up only an estimated 15% of Humira prescriptions, according to a report by Goodroot. 

Adalimumab-ryvk will be launched “imminently” in the United States, according to the press release, but no specific dates were provided. It is also not yet known how the biosimilar will be priced compared with Humira. Other adalimumab biosimilars have launched with discounts from 5% to 85% of Humira’s list price.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved the first interchangeable, high-concentration, citrate-free adalimumab biosimilar, adalimumab-ryvk (Simlandi).

This is the 10th adalimumab biosimilar approved by the regulatory agency and the first biosimilar approval in the US market for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals.

“An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the U.S.,” said Robert Wessman, chairman and CEO of Alvotech, in a company press release on February 23.

Adalimumab-ryvk was approved in the European Union in 2021 and in Australia and Canada in 2022. 

Adalimumab-ryvk is indicated for adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, plaque psoriasis, hidradenitis suppurativa, and noninfectious intermediate and posterior uveitis and panuveitis. In pediatric patients, it is indicated for polyarticular juvenile idiopathic arthritis in children 2 years of age and older and Crohn’s disease in children 6 years of age and older.

Adalimumab-ryvk is the third Humira biosimilar overall granted interchangeability status, which allows pharmacists (depending on state law) to substitute the biosimilar for the reference product without involving the prescribing clinician. Adalimumab-adbm (Cyltezo), manufactured by Boehringer Ingelheim, and adalimumab-afzb (Abrilada), manufactured by Pfizer, were previously granted interchangeability status; however, they both are interchangeable with the low-concentration formulation of Humira, which make up only an estimated 15% of Humira prescriptions, according to a report by Goodroot. 

Adalimumab-ryvk will be launched “imminently” in the United States, according to the press release, but no specific dates were provided. It is also not yet known how the biosimilar will be priced compared with Humira. Other adalimumab biosimilars have launched with discounts from 5% to 85% of Humira’s list price.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved the first interchangeable, high-concentration, citrate-free adalimumab biosimilar, adalimumab-ryvk (Simlandi).

This is the 10th adalimumab biosimilar approved by the regulatory agency and the first biosimilar approval in the US market for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals.

“An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the U.S.,” said Robert Wessman, chairman and CEO of Alvotech, in a company press release on February 23.

Adalimumab-ryvk was approved in the European Union in 2021 and in Australia and Canada in 2022. 

Adalimumab-ryvk is indicated for adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, plaque psoriasis, hidradenitis suppurativa, and noninfectious intermediate and posterior uveitis and panuveitis. In pediatric patients, it is indicated for polyarticular juvenile idiopathic arthritis in children 2 years of age and older and Crohn’s disease in children 6 years of age and older.

Adalimumab-ryvk is the third Humira biosimilar overall granted interchangeability status, which allows pharmacists (depending on state law) to substitute the biosimilar for the reference product without involving the prescribing clinician. Adalimumab-adbm (Cyltezo), manufactured by Boehringer Ingelheim, and adalimumab-afzb (Abrilada), manufactured by Pfizer, were previously granted interchangeability status; however, they both are interchangeable with the low-concentration formulation of Humira, which make up only an estimated 15% of Humira prescriptions, according to a report by Goodroot. 

Adalimumab-ryvk will be launched “imminently” in the United States, according to the press release, but no specific dates were provided. It is also not yet known how the biosimilar will be priced compared with Humira. Other adalimumab biosimilars have launched with discounts from 5% to 85% of Humira’s list price.

A version of this article appeared on Medscape.com.

TOPLINE:

Pooled data from 9225 adults with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no new safety signals with extended exposure to ixekizumab (Taltz).

METHODOLOGY:

• Researchers combined patient data from 25 randomized, controlled trials of the safety and effectiveness of at least one dose of ixekizumab in adults with PsO (n = 6892), PsA (n = 1401), and axSpA (n = 932).
• The study population included patients with a mean age of approximately 43-49 years; at least 49% were male and at least 74% were White across the three conditions.
• Patients’ median duration of ixekizumab exposure was 1.3 years for PsO, 1.4 years for PsA, and 2.7 years for axSpA, with data up to 6 years for PsO and up to 3 years for PsA and axSpA.
• The primary outcomes were exposure-adjusted incidence rates per 100 patient-years overall and at successive year intervals for treatment-emergent adverse events, serious adverse events, and selected adverse events of interest.

TAKEAWAY:

• The incidence rate per 100 person-years for any treatment-emergent adverse event was 32.5 for PsO, 50.3 for PsA, and 38.0 for axSpA; these did not increase with lengthier exposure.
• The incidence rates for serious adverse events for patients with PsO, PsA, or axSpA were 5.4, 6.0, and 4.8 per 100 person-years, respectively.
• A total of 45 deaths were reported across the studies, including 36 in patients with PsO, six with PsA, and three with axSpA.
• Infections were the most common treatment-emergent adverse events across all patient groups, reported in patients at rates of 62.5% with PsO, 52.4% with PsA, and 57.9% with axSpA; incidence of infections did not increase over time.

IN PRACTICE:

“These final, end-of-study program results surrounding the long-term use of [ixekizumab] in patients with PsO, PsA, and axSpA should serve as an important point of reference for physicians considering [ixekizumab],” the researchers wrote.

SOURCE:

The lead author on the study was Atul Deodhar, MD, of Oregon Health & Science University, Portland. The study was published online on February 12 in Arthritis Research & Therapy.

LIMITATIONS:

Study limitations included the small sample sizes and short treatment durations in some studies, the primarily White study population, the inability to stratify risk, the lack of a long-term comparator, and potential survivor bias.

DISCLOSURES:

The studies in the review were supported by Eli Lilly. Lead author Dr. Deodhar disclosed an honorarium and serving on advisory boards at AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, as well as research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Pooled data from 9225 adults with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no new safety signals with extended exposure to ixekizumab (Taltz).

METHODOLOGY:

• Researchers combined patient data from 25 randomized, controlled trials of the safety and effectiveness of at least one dose of ixekizumab in adults with PsO (n = 6892), PsA (n = 1401), and axSpA (n = 932).
• The study population included patients with a mean age of approximately 43-49 years; at least 49% were male and at least 74% were White across the three conditions.
• Patients’ median duration of ixekizumab exposure was 1.3 years for PsO, 1.4 years for PsA, and 2.7 years for axSpA, with data up to 6 years for PsO and up to 3 years for PsA and axSpA.
• The primary outcomes were exposure-adjusted incidence rates per 100 patient-years overall and at successive year intervals for treatment-emergent adverse events, serious adverse events, and selected adverse events of interest.

TAKEAWAY:

• The incidence rate per 100 person-years for any treatment-emergent adverse event was 32.5 for PsO, 50.3 for PsA, and 38.0 for axSpA; these did not increase with lengthier exposure.
• The incidence rates for serious adverse events for patients with PsO, PsA, or axSpA were 5.4, 6.0, and 4.8 per 100 person-years, respectively.
• A total of 45 deaths were reported across the studies, including 36 in patients with PsO, six with PsA, and three with axSpA.
• Infections were the most common treatment-emergent adverse events across all patient groups, reported in patients at rates of 62.5% with PsO, 52.4% with PsA, and 57.9% with axSpA; incidence of infections did not increase over time.

IN PRACTICE:

“These final, end-of-study program results surrounding the long-term use of [ixekizumab] in patients with PsO, PsA, and axSpA should serve as an important point of reference for physicians considering [ixekizumab],” the researchers wrote.

SOURCE:

The lead author on the study was Atul Deodhar, MD, of Oregon Health & Science University, Portland. The study was published online on February 12 in Arthritis Research & Therapy.

LIMITATIONS:

Study limitations included the small sample sizes and short treatment durations in some studies, the primarily White study population, the inability to stratify risk, the lack of a long-term comparator, and potential survivor bias.

DISCLOSURES:

The studies in the review were supported by Eli Lilly. Lead author Dr. Deodhar disclosed an honorarium and serving on advisory boards at AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, as well as research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Pooled data from 9225 adults with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no new safety signals with extended exposure to ixekizumab (Taltz).

METHODOLOGY:

• Researchers combined patient data from 25 randomized, controlled trials of the safety and effectiveness of at least one dose of ixekizumab in adults with PsO (n = 6892), PsA (n = 1401), and axSpA (n = 932).
• The study population included patients with a mean age of approximately 43-49 years; at least 49% were male and at least 74% were White across the three conditions.
• Patients’ median duration of ixekizumab exposure was 1.3 years for PsO, 1.4 years for PsA, and 2.7 years for axSpA, with data up to 6 years for PsO and up to 3 years for PsA and axSpA.
• The primary outcomes were exposure-adjusted incidence rates per 100 patient-years overall and at successive year intervals for treatment-emergent adverse events, serious adverse events, and selected adverse events of interest.

TAKEAWAY:

• The incidence rate per 100 person-years for any treatment-emergent adverse event was 32.5 for PsO, 50.3 for PsA, and 38.0 for axSpA; these did not increase with lengthier exposure.
• The incidence rates for serious adverse events for patients with PsO, PsA, or axSpA were 5.4, 6.0, and 4.8 per 100 person-years, respectively.
• A total of 45 deaths were reported across the studies, including 36 in patients with PsO, six with PsA, and three with axSpA.
• Infections were the most common treatment-emergent adverse events across all patient groups, reported in patients at rates of 62.5% with PsO, 52.4% with PsA, and 57.9% with axSpA; incidence of infections did not increase over time.

IN PRACTICE:

“These final, end-of-study program results surrounding the long-term use of [ixekizumab] in patients with PsO, PsA, and axSpA should serve as an important point of reference for physicians considering [ixekizumab],” the researchers wrote.

SOURCE:

The lead author on the study was Atul Deodhar, MD, of Oregon Health & Science University, Portland. The study was published online on February 12 in Arthritis Research & Therapy.

LIMITATIONS:

Study limitations included the small sample sizes and short treatment durations in some studies, the primarily White study population, the inability to stratify risk, the lack of a long-term comparator, and potential survivor bias.

DISCLOSURES:

The studies in the review were supported by Eli Lilly. Lead author Dr. Deodhar disclosed an honorarium and serving on advisory boards at AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, as well as research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB.
 

A version of this article appeared on Medscape.com.

The smallpox vaccine effectively induces immunity against mpox virus infection (formerly simian smallpox) in patients with human immunodeficiency virus (HIV) infection, although patients with lymphocyte counts below 500 cells/mm³ require booster doses, according to data from a study published in the Journal of Medical Virology.

The data come from the prospective observational study conducted by researchers at the Infection Biology Laboratory of the Department of Medicine and Life Sciences at Pompeu Fabra University and the HIV Unit of the Hospital del Mar Medical Research Institute in Barcelona, Spain. The investigators analyzed T-cell responses induced by vaccination with JYNNEOS.

Despite the substantial decrease in the reporting frequency of mpox cases from the global peak in August 2022 (30,894 cases) to 804 monthly cases in the last six months of 2023, mpox continues to circulate, and there is no specific vaccine. The JYNNEOS vaccine, with protective cross-reactivity against orthopoxviruses, is approved by the US Food and Drug Administration and the European Medicines Agency for the prevention of smallpox and mpox in adults at high risk for infection.

During the 2022 outbreak in the United States and Europe, vaccine shortages led to the emergency use authorization of a lower intradermal dose. This strategy was aimed at increasing vaccine supply up to fivefold.

Further clinical trials are needed to evaluate responses to JYNNEOS vaccination and compare different administration routes in patients with HIV infection. Protecting this population against mpox is a priority because people with high viral loads or loCD4+ T-lymphocyte counts are especially susceptible to severe disease.
 

Vaccination Responses 

The study assessed the immune response to the JYNNEOS vaccine in patients with HIV who were receiving antiretroviral therapy as outpatients at the Infectious Diseases Unit of Hospital del Mar in Barcelona, Spain. Participants had viral loads controlled by antiretroviral therapy and CD4+ T-lymphocyte counts ≤ 500/mm³ (loCD4 group) or ≥ 500/mm³ (hiCD4 group) in blood. Vaccine responses were compared with those of vaccinated controls without the disease. The study included cases that received the standard subcutaneous vaccine (before August 2022) or the emergency dose-saving intradermal vaccine after its approval in August 2022.

The results demonstrated that the intradermal dose-saving vaccination route is preferable to the subcutaneous route and that patients in the loCD4 group may require at least one booster to generate an efficient response of specific T cells for mpox, wrote the authors.

“This study has two relevant points,” study author Robert Güerri-Fernandez, MD, PhD, head of infectious diseases at the Hospital del Mar Medical Research Institute, told this news organization. “In the subgroup of patients with HIV with effective treatment but without an immune response (ie, loCD4), the vaccine response is worse than in people who have recovered immunity or do not have HIV. Therefore, they need a booster dose.

“The second point is that the intradermal route with one-fifth of the standard subcutaneous dose has a better immune response than the standard subcutaneous route.” He added that it was a good strategy to save doses and be able to vaccinate many more people when vaccine shortages occurred.

“A general conclusion cannot be drawn,” he said. “It needs to be validated with many more subjects, of course, but in some way, it reinforced our confidence in the strategy of health authorities to promote intradermal vaccination. There we had evidence that the patients we were vaccinating intradermally were responding well.”

In Spain, although there is no shortage of vaccines today, they continue to be administered intradermally with a fractionated dose equivalent to one fifth of a standard dose, said Dr. Güerri-Fernandez.

However, in his opinion, observations regarding the two administration routes signal a need for further research. The main message should be that for patients with HIV infection who do not have an immune response, the vaccine response is incomplete, and they need booster doses as well as monitoring of the vaccine immune response, said Dr. Güerri-Fernandez.
 

More Studies Required

The research, which prospectively collected data and blood samples from patients with HIV who received the JYNNEOS vaccine, is small and included only 24 patients with HIV infection, with seven hospital workers who also received the vaccine and seven unvaccinated individuals as controls. “I am one of the control subjects of the study, and intradermal vaccination is not especially pleasant,” said Dr. Güerri-Fernandez. “It is a very innervated area, and the moment of introducing the liquid is uncomfortable. But it is perfectly bearable.”

Outpatient HIV-infected patients from the Infectious Diseases Unit of Hospital del Mar on antiretroviral therapy and with undetectable viral loads were grouped according to their CD4+ T-lymphocyte counts. Those with CD4+ T-lymphocyte counts ≤ 500/mm³ required at least one booster vaccine to exhibit efficient virus-specific T-lymphocyte responses. The magnitude of the T-cell response after this booster correlated directly with the CD4+ T-lymphocyte count of those vaccinated.

For Argentine infectious disease specialist Julián García, MD, clinical researcher at the Huésped Foundation in Buenos Aires, Argentina, who did not participate in the study, it is always productive to know that T-cell responses develop in patients with HIV infection, with CD4+ T-lymphocyte counts > and < 500/mm^3, through an intradermal administration route.

Dr. García emphasized that the most novel aspect is that the JYNNEOS vaccine induces a specific T-cell response in patients with HIV infection that increases with higher CD4+ T-lymphocyte levels. However, he noted that the number of patients was less than 10 in most study groups, and the control group had only intradermal administration, which limits the interpretation of the results. “It will be necessary to verify this in studies with larger groups with control groups from all routes and with a correlate of protection.”

Dr. García referred to this latter point as a significant source of uncertainty. “The study is fundamentally based on the cellular response, but nowadays, there is no immune correlate of real-life protection.” He concluded that the study builds knowledge, which is essential for a vaccine that began to be used for mpox and the effectiveness of which is based on estimates. 

Dr. Güerri-Fernandez and Dr. Garcia declared no relevant financial conflicts of interest. 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The smallpox vaccine effectively induces immunity against mpox virus infection (formerly simian smallpox) in patients with human immunodeficiency virus (HIV) infection, although patients with lymphocyte counts below 500 cells/mm³ require booster doses, according to data from a study published in the Journal of Medical Virology.

The data come from the prospective observational study conducted by researchers at the Infection Biology Laboratory of the Department of Medicine and Life Sciences at Pompeu Fabra University and the HIV Unit of the Hospital del Mar Medical Research Institute in Barcelona, Spain. The investigators analyzed T-cell responses induced by vaccination with JYNNEOS.

Despite the substantial decrease in the reporting frequency of mpox cases from the global peak in August 2022 (30,894 cases) to 804 monthly cases in the last six months of 2023, mpox continues to circulate, and there is no specific vaccine. The JYNNEOS vaccine, with protective cross-reactivity against orthopoxviruses, is approved by the US Food and Drug Administration and the European Medicines Agency for the prevention of smallpox and mpox in adults at high risk for infection.

During the 2022 outbreak in the United States and Europe, vaccine shortages led to the emergency use authorization of a lower intradermal dose. This strategy was aimed at increasing vaccine supply up to fivefold.

Further clinical trials are needed to evaluate responses to JYNNEOS vaccination and compare different administration routes in patients with HIV infection. Protecting this population against mpox is a priority because people with high viral loads or loCD4+ T-lymphocyte counts are especially susceptible to severe disease.
 

Vaccination Responses 

The study assessed the immune response to the JYNNEOS vaccine in patients with HIV who were receiving antiretroviral therapy as outpatients at the Infectious Diseases Unit of Hospital del Mar in Barcelona, Spain. Participants had viral loads controlled by antiretroviral therapy and CD4+ T-lymphocyte counts ≤ 500/mm³ (loCD4 group) or ≥ 500/mm³ (hiCD4 group) in blood. Vaccine responses were compared with those of vaccinated controls without the disease. The study included cases that received the standard subcutaneous vaccine (before August 2022) or the emergency dose-saving intradermal vaccine after its approval in August 2022.

The results demonstrated that the intradermal dose-saving vaccination route is preferable to the subcutaneous route and that patients in the loCD4 group may require at least one booster to generate an efficient response of specific T cells for mpox, wrote the authors.

“This study has two relevant points,” study author Robert Güerri-Fernandez, MD, PhD, head of infectious diseases at the Hospital del Mar Medical Research Institute, told this news organization. “In the subgroup of patients with HIV with effective treatment but without an immune response (ie, loCD4), the vaccine response is worse than in people who have recovered immunity or do not have HIV. Therefore, they need a booster dose.

“The second point is that the intradermal route with one-fifth of the standard subcutaneous dose has a better immune response than the standard subcutaneous route.” He added that it was a good strategy to save doses and be able to vaccinate many more people when vaccine shortages occurred.

“A general conclusion cannot be drawn,” he said. “It needs to be validated with many more subjects, of course, but in some way, it reinforced our confidence in the strategy of health authorities to promote intradermal vaccination. There we had evidence that the patients we were vaccinating intradermally were responding well.”

In Spain, although there is no shortage of vaccines today, they continue to be administered intradermally with a fractionated dose equivalent to one fifth of a standard dose, said Dr. Güerri-Fernandez.

However, in his opinion, observations regarding the two administration routes signal a need for further research. The main message should be that for patients with HIV infection who do not have an immune response, the vaccine response is incomplete, and they need booster doses as well as monitoring of the vaccine immune response, said Dr. Güerri-Fernandez.
 

More Studies Required

The research, which prospectively collected data and blood samples from patients with HIV who received the JYNNEOS vaccine, is small and included only 24 patients with HIV infection, with seven hospital workers who also received the vaccine and seven unvaccinated individuals as controls. “I am one of the control subjects of the study, and intradermal vaccination is not especially pleasant,” said Dr. Güerri-Fernandez. “It is a very innervated area, and the moment of introducing the liquid is uncomfortable. But it is perfectly bearable.”

Outpatient HIV-infected patients from the Infectious Diseases Unit of Hospital del Mar on antiretroviral therapy and with undetectable viral loads were grouped according to their CD4+ T-lymphocyte counts. Those with CD4+ T-lymphocyte counts ≤ 500/mm³ required at least one booster vaccine to exhibit efficient virus-specific T-lymphocyte responses. The magnitude of the T-cell response after this booster correlated directly with the CD4+ T-lymphocyte count of those vaccinated.

For Argentine infectious disease specialist Julián García, MD, clinical researcher at the Huésped Foundation in Buenos Aires, Argentina, who did not participate in the study, it is always productive to know that T-cell responses develop in patients with HIV infection, with CD4+ T-lymphocyte counts > and < 500/mm^3, through an intradermal administration route.

Dr. García emphasized that the most novel aspect is that the JYNNEOS vaccine induces a specific T-cell response in patients with HIV infection that increases with higher CD4+ T-lymphocyte levels. However, he noted that the number of patients was less than 10 in most study groups, and the control group had only intradermal administration, which limits the interpretation of the results. “It will be necessary to verify this in studies with larger groups with control groups from all routes and with a correlate of protection.”

Dr. García referred to this latter point as a significant source of uncertainty. “The study is fundamentally based on the cellular response, but nowadays, there is no immune correlate of real-life protection.” He concluded that the study builds knowledge, which is essential for a vaccine that began to be used for mpox and the effectiveness of which is based on estimates. 

Dr. Güerri-Fernandez and Dr. Garcia declared no relevant financial conflicts of interest. 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The smallpox vaccine effectively induces immunity against mpox virus infection (formerly simian smallpox) in patients with human immunodeficiency virus (HIV) infection, although patients with lymphocyte counts below 500 cells/mm³ require booster doses, according to data from a study published in the Journal of Medical Virology.

The data come from the prospective observational study conducted by researchers at the Infection Biology Laboratory of the Department of Medicine and Life Sciences at Pompeu Fabra University and the HIV Unit of the Hospital del Mar Medical Research Institute in Barcelona, Spain. The investigators analyzed T-cell responses induced by vaccination with JYNNEOS.

Despite the substantial decrease in the reporting frequency of mpox cases from the global peak in August 2022 (30,894 cases) to 804 monthly cases in the last six months of 2023, mpox continues to circulate, and there is no specific vaccine. The JYNNEOS vaccine, with protective cross-reactivity against orthopoxviruses, is approved by the US Food and Drug Administration and the European Medicines Agency for the prevention of smallpox and mpox in adults at high risk for infection.

During the 2022 outbreak in the United States and Europe, vaccine shortages led to the emergency use authorization of a lower intradermal dose. This strategy was aimed at increasing vaccine supply up to fivefold.

Further clinical trials are needed to evaluate responses to JYNNEOS vaccination and compare different administration routes in patients with HIV infection. Protecting this population against mpox is a priority because people with high viral loads or loCD4+ T-lymphocyte counts are especially susceptible to severe disease.
 

Vaccination Responses 

The study assessed the immune response to the JYNNEOS vaccine in patients with HIV who were receiving antiretroviral therapy as outpatients at the Infectious Diseases Unit of Hospital del Mar in Barcelona, Spain. Participants had viral loads controlled by antiretroviral therapy and CD4+ T-lymphocyte counts ≤ 500/mm³ (loCD4 group) or ≥ 500/mm³ (hiCD4 group) in blood. Vaccine responses were compared with those of vaccinated controls without the disease. The study included cases that received the standard subcutaneous vaccine (before August 2022) or the emergency dose-saving intradermal vaccine after its approval in August 2022.

The results demonstrated that the intradermal dose-saving vaccination route is preferable to the subcutaneous route and that patients in the loCD4 group may require at least one booster to generate an efficient response of specific T cells for mpox, wrote the authors.

“This study has two relevant points,” study author Robert Güerri-Fernandez, MD, PhD, head of infectious diseases at the Hospital del Mar Medical Research Institute, told this news organization. “In the subgroup of patients with HIV with effective treatment but without an immune response (ie, loCD4), the vaccine response is worse than in people who have recovered immunity or do not have HIV. Therefore, they need a booster dose.

“The second point is that the intradermal route with one-fifth of the standard subcutaneous dose has a better immune response than the standard subcutaneous route.” He added that it was a good strategy to save doses and be able to vaccinate many more people when vaccine shortages occurred.

“A general conclusion cannot be drawn,” he said. “It needs to be validated with many more subjects, of course, but in some way, it reinforced our confidence in the strategy of health authorities to promote intradermal vaccination. There we had evidence that the patients we were vaccinating intradermally were responding well.”

In Spain, although there is no shortage of vaccines today, they continue to be administered intradermally with a fractionated dose equivalent to one fifth of a standard dose, said Dr. Güerri-Fernandez.

However, in his opinion, observations regarding the two administration routes signal a need for further research. The main message should be that for patients with HIV infection who do not have an immune response, the vaccine response is incomplete, and they need booster doses as well as monitoring of the vaccine immune response, said Dr. Güerri-Fernandez.
 

More Studies Required

The research, which prospectively collected data and blood samples from patients with HIV who received the JYNNEOS vaccine, is small and included only 24 patients with HIV infection, with seven hospital workers who also received the vaccine and seven unvaccinated individuals as controls. “I am one of the control subjects of the study, and intradermal vaccination is not especially pleasant,” said Dr. Güerri-Fernandez. “It is a very innervated area, and the moment of introducing the liquid is uncomfortable. But it is perfectly bearable.”

Outpatient HIV-infected patients from the Infectious Diseases Unit of Hospital del Mar on antiretroviral therapy and with undetectable viral loads were grouped according to their CD4+ T-lymphocyte counts. Those with CD4+ T-lymphocyte counts ≤ 500/mm³ required at least one booster vaccine to exhibit efficient virus-specific T-lymphocyte responses. The magnitude of the T-cell response after this booster correlated directly with the CD4+ T-lymphocyte count of those vaccinated.

For Argentine infectious disease specialist Julián García, MD, clinical researcher at the Huésped Foundation in Buenos Aires, Argentina, who did not participate in the study, it is always productive to know that T-cell responses develop in patients with HIV infection, with CD4+ T-lymphocyte counts > and < 500/mm^3, through an intradermal administration route.

Dr. García emphasized that the most novel aspect is that the JYNNEOS vaccine induces a specific T-cell response in patients with HIV infection that increases with higher CD4+ T-lymphocyte levels. However, he noted that the number of patients was less than 10 in most study groups, and the control group had only intradermal administration, which limits the interpretation of the results. “It will be necessary to verify this in studies with larger groups with control groups from all routes and with a correlate of protection.”

Dr. García referred to this latter point as a significant source of uncertainty. “The study is fundamentally based on the cellular response, but nowadays, there is no immune correlate of real-life protection.” He concluded that the study builds knowledge, which is essential for a vaccine that began to be used for mpox and the effectiveness of which is based on estimates. 

Dr. Güerri-Fernandez and Dr. Garcia declared no relevant financial conflicts of interest. 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Communicating bad news to patients is one of the most stressful and challenging clinical tasks for any physician, regardless of his or her specialty. Delivering bad news to a patient or their close relative is demanding because the information provided during the dialogue can substantially alter the person’s perspective on life. This task is more frequent for physicians caring for oncology patients and can also affect the physician’s emotional state.

The manner in which bad news is communicated plays a significant role in the psychological burden on the patient, and various communication techniques and guidelines have been developed to enable physicians to perform this difficult task effectively.

Revealing bad news in person whenever possible, to address the emotional responses of patients or relatives, is part of the prevailing expert recommendations. However, it has been acknowledged that in certain situations, communicating bad news over the phone is more feasible.

Since the beginning of the COVID-19 pandemic, the disclosure of bad news over the phone has become a necessary substitute for in-person visits and an integral part of clinical practice worldwide. It remains to be clarified what the real psychological impact on patients and their closest relatives is when delivering bad news over the phone compared with delivering it in person.

Right and Wrong Ways

The most popular guideline for communicating bad news is SPIKES, a six-phase protocol with a special application for cancer patients. It is used in various countries (eg, the United States, France, and Germany) as a guide for this sensitive practice and for training in communication skills in this context. The SPIKES acronym refers to the following six recommended steps for delivering bad news:

• Setting: Set up the conversation.
• Perception: Assess the patient’s perception.
• Invitation: Ask the patient what he or she would like to know.
• Knowledge: Provide the patient with knowledge and information, breaking it down into small parts.
• Emotions: Acknowledge and empathetically address the patient’s emotions.
• Strategy and Summary: Summarize and define a medical action plan.

The lesson from SPIKES is that when a person experiences strong emotions, it is difficult to continue discussing anything, and they will struggle to hear anything. Allowing for silence is fundamental. In addition, empathy allows the patient to express his or her feelings and concerns, as well as provide support. The aim is not to argue but to allow the expression of emotions without criticism. However, these recommendations are primarily based on expert opinion and less on empirical evidence, due to the difficulty of studies in assessing patient outcomes in various phases of these protocols.

A recent study analyzed the differences in psychological distress between patients who received bad news over the phone vs those who received it in person. The study was a systematic review and meta-analysis.

The investigators examined 5944 studies, including 11 qualitative analysis studies, nine meta-analyses, and four randomized controlled trials.

In a set of studies ranging from moderate to good quality, no difference in psychological distress was found when bad news was disclosed over the phone compared with in person, regarding anxiety, depression, and posttraumatic stress disorder.

There was no average difference in patient satisfaction levels when bad news was delivered over the phone compared with in person. The risk for dissatisfaction was similar between groups.

Clinical Practice Guidelines

The demand for telemedicine, including the disclosure of bad news, is growing despite the limited knowledge of potential adverse effects. The results of existing studies suggest that the mode of disclosure may play a secondary role, and the manner in which bad news is communicated may be more important.

Therefore, it is paramount to prepare patients or their families for the possibility of receiving bad news well in advance and, during the conversation, to ensure first and foremost that they are in an appropriate environment. The structure and content of the conversation may be relevant, and adhering to dedicated communication strategies can be a wise choice for the physician and the interlocutor.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Communicating bad news to patients is one of the most stressful and challenging clinical tasks for any physician, regardless of his or her specialty. Delivering bad news to a patient or their close relative is demanding because the information provided during the dialogue can substantially alter the person’s perspective on life. This task is more frequent for physicians caring for oncology patients and can also affect the physician’s emotional state.

The manner in which bad news is communicated plays a significant role in the psychological burden on the patient, and various communication techniques and guidelines have been developed to enable physicians to perform this difficult task effectively.

Revealing bad news in person whenever possible, to address the emotional responses of patients or relatives, is part of the prevailing expert recommendations. However, it has been acknowledged that in certain situations, communicating bad news over the phone is more feasible.

Since the beginning of the COVID-19 pandemic, the disclosure of bad news over the phone has become a necessary substitute for in-person visits and an integral part of clinical practice worldwide. It remains to be clarified what the real psychological impact on patients and their closest relatives is when delivering bad news over the phone compared with delivering it in person.

Right and Wrong Ways

The most popular guideline for communicating bad news is SPIKES, a six-phase protocol with a special application for cancer patients. It is used in various countries (eg, the United States, France, and Germany) as a guide for this sensitive practice and for training in communication skills in this context. The SPIKES acronym refers to the following six recommended steps for delivering bad news:

• Setting: Set up the conversation.
• Perception: Assess the patient’s perception.
• Invitation: Ask the patient what he or she would like to know.
• Knowledge: Provide the patient with knowledge and information, breaking it down into small parts.
• Emotions: Acknowledge and empathetically address the patient’s emotions.
• Strategy and Summary: Summarize and define a medical action plan.

The lesson from SPIKES is that when a person experiences strong emotions, it is difficult to continue discussing anything, and they will struggle to hear anything. Allowing for silence is fundamental. In addition, empathy allows the patient to express his or her feelings and concerns, as well as provide support. The aim is not to argue but to allow the expression of emotions without criticism. However, these recommendations are primarily based on expert opinion and less on empirical evidence, due to the difficulty of studies in assessing patient outcomes in various phases of these protocols.

A recent study analyzed the differences in psychological distress between patients who received bad news over the phone vs those who received it in person. The study was a systematic review and meta-analysis.

The investigators examined 5944 studies, including 11 qualitative analysis studies, nine meta-analyses, and four randomized controlled trials.

In a set of studies ranging from moderate to good quality, no difference in psychological distress was found when bad news was disclosed over the phone compared with in person, regarding anxiety, depression, and posttraumatic stress disorder.

There was no average difference in patient satisfaction levels when bad news was delivered over the phone compared with in person. The risk for dissatisfaction was similar between groups.

Clinical Practice Guidelines

The demand for telemedicine, including the disclosure of bad news, is growing despite the limited knowledge of potential adverse effects. The results of existing studies suggest that the mode of disclosure may play a secondary role, and the manner in which bad news is communicated may be more important.

Therefore, it is paramount to prepare patients or their families for the possibility of receiving bad news well in advance and, during the conversation, to ensure first and foremost that they are in an appropriate environment. The structure and content of the conversation may be relevant, and adhering to dedicated communication strategies can be a wise choice for the physician and the interlocutor.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Communicating bad news to patients is one of the most stressful and challenging clinical tasks for any physician, regardless of his or her specialty. Delivering bad news to a patient or their close relative is demanding because the information provided during the dialogue can substantially alter the person’s perspective on life. This task is more frequent for physicians caring for oncology patients and can also affect the physician’s emotional state.

The manner in which bad news is communicated plays a significant role in the psychological burden on the patient, and various communication techniques and guidelines have been developed to enable physicians to perform this difficult task effectively.

Revealing bad news in person whenever possible, to address the emotional responses of patients or relatives, is part of the prevailing expert recommendations. However, it has been acknowledged that in certain situations, communicating bad news over the phone is more feasible.

Since the beginning of the COVID-19 pandemic, the disclosure of bad news over the phone has become a necessary substitute for in-person visits and an integral part of clinical practice worldwide. It remains to be clarified what the real psychological impact on patients and their closest relatives is when delivering bad news over the phone compared with delivering it in person.

Right and Wrong Ways

The most popular guideline for communicating bad news is SPIKES, a six-phase protocol with a special application for cancer patients. It is used in various countries (eg, the United States, France, and Germany) as a guide for this sensitive practice and for training in communication skills in this context. The SPIKES acronym refers to the following six recommended steps for delivering bad news:

• Setting: Set up the conversation.
• Perception: Assess the patient’s perception.
• Invitation: Ask the patient what he or she would like to know.
• Knowledge: Provide the patient with knowledge and information, breaking it down into small parts.
• Emotions: Acknowledge and empathetically address the patient’s emotions.
• Strategy and Summary: Summarize and define a medical action plan.

The lesson from SPIKES is that when a person experiences strong emotions, it is difficult to continue discussing anything, and they will struggle to hear anything. Allowing for silence is fundamental. In addition, empathy allows the patient to express his or her feelings and concerns, as well as provide support. The aim is not to argue but to allow the expression of emotions without criticism. However, these recommendations are primarily based on expert opinion and less on empirical evidence, due to the difficulty of studies in assessing patient outcomes in various phases of these protocols.

A recent study analyzed the differences in psychological distress between patients who received bad news over the phone vs those who received it in person. The study was a systematic review and meta-analysis.

The investigators examined 5944 studies, including 11 qualitative analysis studies, nine meta-analyses, and four randomized controlled trials.

In a set of studies ranging from moderate to good quality, no difference in psychological distress was found when bad news was disclosed over the phone compared with in person, regarding anxiety, depression, and posttraumatic stress disorder.

There was no average difference in patient satisfaction levels when bad news was delivered over the phone compared with in person. The risk for dissatisfaction was similar between groups.

Clinical Practice Guidelines

The demand for telemedicine, including the disclosure of bad news, is growing despite the limited knowledge of potential adverse effects. The results of existing studies suggest that the mode of disclosure may play a secondary role, and the manner in which bad news is communicated may be more important.

Therefore, it is paramount to prepare patients or their families for the possibility of receiving bad news well in advance and, during the conversation, to ensure first and foremost that they are in an appropriate environment. The structure and content of the conversation may be relevant, and adhering to dedicated communication strategies can be a wise choice for the physician and the interlocutor.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.

A study found that results from 475 clinical trials in Denmark, Iceland, Finland, Norway, and Sweden — involving almost 84,000 participants — were never made public in any form.

Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said. 

There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
 

Research Waste Is a ‘Pervasive Problem’

So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.

The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.

Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”

Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
 

The Case for Laws, Monitoring, and Fines

Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.” 

Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”

Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”

He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.

Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.

In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.

Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
 

‘Rampant Noncompliance’ in the United States

In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.

The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.

The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.

The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.

Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
 

A version of this article appeared on Medscape.com.

Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.

A study found that results from 475 clinical trials in Denmark, Iceland, Finland, Norway, and Sweden — involving almost 84,000 participants — were never made public in any form.

Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said. 

There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
 

Research Waste Is a ‘Pervasive Problem’

So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.

The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.

Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”

Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
 

The Case for Laws, Monitoring, and Fines

Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.” 

Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”

Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”

He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.

Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.

In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.

Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
 

‘Rampant Noncompliance’ in the United States

In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.

The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.

The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.

The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.

Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
 

A version of this article appeared on Medscape.com.

Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.

A study found that results from 475 clinical trials in Denmark, Iceland, Finland, Norway, and Sweden — involving almost 84,000 participants — were never made public in any form.

Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said. 

There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
 

Research Waste Is a ‘Pervasive Problem’

So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.

The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.

Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”

Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
 

The Case for Laws, Monitoring, and Fines

Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.” 

Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”

Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”

He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.

Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.

In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.

Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
 

‘Rampant Noncompliance’ in the United States

In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.

The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.

The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.

The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.

Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
 

A version of this article appeared on Medscape.com.

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

A group of 16 Democratic legislators on the House Committee on Oversight and Reform has demanded in a letter that the drugmaker Pfizer present details on how the company is responding to shortages of the generic chemotherapy drugs carboplatin, cisplatin, and methotrexate.

In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.

A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”

What is the basis for concern?

All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.

What has the government done in response to the recent shortages?

The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.

What can the lawmakers expect to achieve with their letter?

By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”

Why did the committee target Pfizer specifically?

Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”

The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.

What is being demanded of Pfizer?

Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.

A group of 16 Democratic legislators on the House Committee on Oversight and Reform has demanded in a letter that the drugmaker Pfizer present details on how the company is responding to shortages of the generic chemotherapy drugs carboplatin, cisplatin, and methotrexate.

In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.

A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”

What is the basis for concern?

All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.

What has the government done in response to the recent shortages?

The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.

What can the lawmakers expect to achieve with their letter?

By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”

Why did the committee target Pfizer specifically?

Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”

The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.

What is being demanded of Pfizer?

Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.

A group of 16 Democratic legislators on the House Committee on Oversight and Reform has demanded in a letter that the drugmaker Pfizer present details on how the company is responding to shortages of the generic chemotherapy drugs carboplatin, cisplatin, and methotrexate.

In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.

A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”

What is the basis for concern?

All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.

What has the government done in response to the recent shortages?

The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.

What can the lawmakers expect to achieve with their letter?

By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”

Why did the committee target Pfizer specifically?

Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”

The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.

What is being demanded of Pfizer?

Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Age older than 65 years and serum creatinine greater than 140 micromol/L at the time of systemic polyarteritis nodosa (PAN) diagnosis were significant predictors of mortality.

METHODOLOGY:

• A total of 358 patients diagnosed with PAN between 1990 and 2020 were identified from retrospective chart reviews and prospective cohorts from nine countries as a part of GLOBAL-PAN, a collaboration of the European Vasculitis Society, the Vasculitis Clinical Research Consortium, and other networks.
• The goal of the retrospective chart review was to characterize the nature, presentation, and survival rates of patients with PAN.
• The study population included 174 female and 184 male patients; 282 had systemic PAN (sPAN) and 76 had cutaneous PAN (cPAN); the mean age at diagnosis was 44.3 years.

TAKEAWAY:

• Overall survival rates at 1, 5, and 10 years for patients with sPAN were 97.1%, 94.0%, and 89.0%, respectively.
• Significant independent predictors of mortality were age ≥ 65 years at the time of sPAN diagnosis (hazard ratio [HR], 3.85), serum creatinine > 140 micromol/L at the time of diagnosis (HR, 4.93), gastrointestinal involvement (HR, 3.51), and central nervous system involvement (HR, 3.56).
• Constitutional symptoms were significantly more common in patients with sPAN vs cPAN (78.8% vs 44.7%), while patients with cPAN were significantly more likely to be female and have more skin nodules than patients with sPAN.
• Relapse over a median disease duration of 59.6 months was slightly higher for cPAN vs sPAN (38.8% vs 32.1%).

IN PRACTICE:

“This study helps better define the demographic and clinical characteristics of patients with PAN and differentiates sPAN from cPAN,” the researchers wrote.

SOURCE:

The lead author of the study was Omer Karadag, MD, of Hacettepe University, Ankara, Turkey. The study was published online on February 12 in Arthritis & Rheumatology.

LIMITATIONS:

Study limitations included the combination of prospective and retrospective data, varying approaches to patient assessment, and lack of data on treatment effects.

DISCLOSURES:

The study was supported by the Vasculitis Clinical Research Consortium, which received funding from the National Center for Advancing Translational Science, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Center for Research Resources. Dr. Karadag disclosed research grants from AbbVie, Novartis, Viela-Bio, and TR-Pharma, and consulting fees from AbbVie, Abdi Ibrahim, Celltrion, Novartis, Pfizer, Sandoz, and UCB.

A version of this article appeared on Medscape.com.

TOPLINE:

Age older than 65 years and serum creatinine greater than 140 micromol/L at the time of systemic polyarteritis nodosa (PAN) diagnosis were significant predictors of mortality.

METHODOLOGY:

• A total of 358 patients diagnosed with PAN between 1990 and 2020 were identified from retrospective chart reviews and prospective cohorts from nine countries as a part of GLOBAL-PAN, a collaboration of the European Vasculitis Society, the Vasculitis Clinical Research Consortium, and other networks.
• The goal of the retrospective chart review was to characterize the nature, presentation, and survival rates of patients with PAN.
• The study population included 174 female and 184 male patients; 282 had systemic PAN (sPAN) and 76 had cutaneous PAN (cPAN); the mean age at diagnosis was 44.3 years.

TAKEAWAY:

• Overall survival rates at 1, 5, and 10 years for patients with sPAN were 97.1%, 94.0%, and 89.0%, respectively.
• Significant independent predictors of mortality were age ≥ 65 years at the time of sPAN diagnosis (hazard ratio [HR], 3.85), serum creatinine > 140 micromol/L at the time of diagnosis (HR, 4.93), gastrointestinal involvement (HR, 3.51), and central nervous system involvement (HR, 3.56).
• Constitutional symptoms were significantly more common in patients with sPAN vs cPAN (78.8% vs 44.7%), while patients with cPAN were significantly more likely to be female and have more skin nodules than patients with sPAN.
• Relapse over a median disease duration of 59.6 months was slightly higher for cPAN vs sPAN (38.8% vs 32.1%).

IN PRACTICE:

“This study helps better define the demographic and clinical characteristics of patients with PAN and differentiates sPAN from cPAN,” the researchers wrote.

SOURCE:

The lead author of the study was Omer Karadag, MD, of Hacettepe University, Ankara, Turkey. The study was published online on February 12 in Arthritis & Rheumatology.

LIMITATIONS:

Study limitations included the combination of prospective and retrospective data, varying approaches to patient assessment, and lack of data on treatment effects.

DISCLOSURES:

The study was supported by the Vasculitis Clinical Research Consortium, which received funding from the National Center for Advancing Translational Science, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Center for Research Resources. Dr. Karadag disclosed research grants from AbbVie, Novartis, Viela-Bio, and TR-Pharma, and consulting fees from AbbVie, Abdi Ibrahim, Celltrion, Novartis, Pfizer, Sandoz, and UCB.

A version of this article appeared on Medscape.com.

TOPLINE:

Age older than 65 years and serum creatinine greater than 140 micromol/L at the time of systemic polyarteritis nodosa (PAN) diagnosis were significant predictors of mortality.

METHODOLOGY:

• A total of 358 patients diagnosed with PAN between 1990 and 2020 were identified from retrospective chart reviews and prospective cohorts from nine countries as a part of GLOBAL-PAN, a collaboration of the European Vasculitis Society, the Vasculitis Clinical Research Consortium, and other networks.
• The goal of the retrospective chart review was to characterize the nature, presentation, and survival rates of patients with PAN.
• The study population included 174 female and 184 male patients; 282 had systemic PAN (sPAN) and 76 had cutaneous PAN (cPAN); the mean age at diagnosis was 44.3 years.

TAKEAWAY:

• Overall survival rates at 1, 5, and 10 years for patients with sPAN were 97.1%, 94.0%, and 89.0%, respectively.
• Significant independent predictors of mortality were age ≥ 65 years at the time of sPAN diagnosis (hazard ratio [HR], 3.85), serum creatinine > 140 micromol/L at the time of diagnosis (HR, 4.93), gastrointestinal involvement (HR, 3.51), and central nervous system involvement (HR, 3.56).
• Constitutional symptoms were significantly more common in patients with sPAN vs cPAN (78.8% vs 44.7%), while patients with cPAN were significantly more likely to be female and have more skin nodules than patients with sPAN.
• Relapse over a median disease duration of 59.6 months was slightly higher for cPAN vs sPAN (38.8% vs 32.1%).

IN PRACTICE:

“This study helps better define the demographic and clinical characteristics of patients with PAN and differentiates sPAN from cPAN,” the researchers wrote.

SOURCE:

The lead author of the study was Omer Karadag, MD, of Hacettepe University, Ankara, Turkey. The study was published online on February 12 in Arthritis & Rheumatology.

LIMITATIONS:

Study limitations included the combination of prospective and retrospective data, varying approaches to patient assessment, and lack of data on treatment effects.

DISCLOSURES:

The study was supported by the Vasculitis Clinical Research Consortium, which received funding from the National Center for Advancing Translational Science, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Center for Research Resources. Dr. Karadag disclosed research grants from AbbVie, Novartis, Viela-Bio, and TR-Pharma, and consulting fees from AbbVie, Abdi Ibrahim, Celltrion, Novartis, Pfizer, Sandoz, and UCB.

A version of this article appeared on Medscape.com.