Rheumatology

The presence of antiphospholipid antibodies is associated with an increased risk for future cardiovascular events, according to a new study.

The findings point to possible new approaches to risk stratification and the potential for new therapeutic targets in heart disease.

“In this study of the general population, we found that two antiphospholipid antibodies were associated with an increased risk of having a serious cardiovascular event over a follow-up of 8 years,” coauthor Jason Knight, MD, University of Michigan, Ann Arbor, said in an interview.

“If confirmed in further studies, these findings could be used to identify a subgroup of patients who need more careful monitoring and more aggressive risk-factor modification, and if the increased risk linked to these antibodies is high enough, it may also justify preemptive treatments such as the anticoagulants that are routinely used in antiphospholipid syndrome,” Dr. Knight said.

“The long-term vision is that we may identify some people in the general population who would benefit from treating the immune system for the prevention and treatment of cardiovascular disease instead of, or in addition to, using typical cardiovascular medications,” he added.

The study was published online in JAMA Network Open.

Individuals with autoimmune and inflammatory diseases have a greater risk for cardiovascular events than expected based on traditional cardiovascular risk factors, with mechanisms proposed to explain this risk including inflammation-mediated disruption of vascular integrity and activation of platelets and coagulation pathways, the authors explained. However, the role of autoantibodies remains unclear.

They noted that antiphospholipid antibodies can activate endothelial cells, platelets, and neutrophils, and some patients with persistently circulating antiphospholipid antibodies can develop antiphospholipid syndrome – an acquired thromboinflammatory disease characterized by arterial, venous, and microvascular thrombotic events and obstetric complications.

Cross-sectional studies have shown that antiphospholipid antibodies are acutely present in up to 17.4% of patients with stroke or transient ischemic attack, and small cohort studies have suggested that such antibodies may be present in 1%-12% of seemingly healthy individuals. However, the impact of sex, race, and ethnicity on the prevalence of antiphospholipid antibodies and their association with atherosclerotic cardiovascular disease is not known.

The researchers conducted the current study to look at the association between antiphospholipid antibodies and future risk for atherosclerotic cardiovascular events.

They analyzed data from 2,427 participants in the population-based Dallas Heart Study who had no history of atherosclerotic cardiovascular disease or autoimmune diseases requiring immunosuppressive medications at the time of blood sampling at study entry in 2007-2009.

Eight different types of antiphospholipid antibodies were measured, and data on cardiovascular events over the next 8 years was recorded.

Results showed that 14.5% of the cohort tested positive for one of these antiphospholipid antibodies at the start of the study, with approximately one-third of those detected at a moderate or high titer.

The researchers also found that the IgA isotypes of two antiphospholipid antibodies – anticardiolipin and anti-beta-2 glycoprotein – were associated with future atherosclerotic cardiovascular events.

After adjustment for other known risk factors, individuals testing positive for the IgA isotype of anticardiolipin had an almost five times increased risk (hazard ratio, 4.92) of the primary endpoint (myocardial infarction, stroke, coronary revascularization, or cardiovascular death); while those testing positive for anti–beta₂-glycoprotein had an almost three times increased risk (HR, 2.91).

Furthermore, there was what appeared to be a dose effect. People with the highest levels of these antibodies also had the highest risk for cardiovascular events, with up to an almost 10-fold increased risk with the higher level of anticardiolipin. 

Dr. Knight said that more research into the IgA isotypes of these antiphospholipid antibodies is needed.

“Most of the mechanistic work in the antiphospholipid syndrome field has focused on IgG antiphospholipid antibodies. While we commonly find these IgA antibodies in patients with APS, the extent to which they contribute to disease has not been firmly established,” he said. “The fact that IgA was the primary hit in our unbiased screen suggests that there is more to the story and we need to better understand the implications of having these antibodies in circulation, and what specific problems they may be causing.”

Noting that antiphospholipid antibodies can form transiently after certain situations, such as infections, Dr. Knight said that further studies were needed with repeat blood testing to detect the chronic presence of the antibodies.

He added that information of venous thromboses was not available in this study and “perhaps some of the other antibodies might have stood out if we were able to analyze for different outcomes.”

This study was supported by a Pfizer Aspire Award. Dr. Knight reported receiving research funding and consulting fees from Jazz Pharmaceuticals outside the submitted work.

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

The presence of antiphospholipid antibodies is associated with an increased risk for future cardiovascular events, according to a new study.

The findings point to possible new approaches to risk stratification and the potential for new therapeutic targets in heart disease.

“In this study of the general population, we found that two antiphospholipid antibodies were associated with an increased risk of having a serious cardiovascular event over a follow-up of 8 years,” coauthor Jason Knight, MD, University of Michigan, Ann Arbor, said in an interview.

“If confirmed in further studies, these findings could be used to identify a subgroup of patients who need more careful monitoring and more aggressive risk-factor modification, and if the increased risk linked to these antibodies is high enough, it may also justify preemptive treatments such as the anticoagulants that are routinely used in antiphospholipid syndrome,” Dr. Knight said.

“The long-term vision is that we may identify some people in the general population who would benefit from treating the immune system for the prevention and treatment of cardiovascular disease instead of, or in addition to, using typical cardiovascular medications,” he added.

The study was published online in JAMA Network Open.

Individuals with autoimmune and inflammatory diseases have a greater risk for cardiovascular events than expected based on traditional cardiovascular risk factors, with mechanisms proposed to explain this risk including inflammation-mediated disruption of vascular integrity and activation of platelets and coagulation pathways, the authors explained. However, the role of autoantibodies remains unclear.

They noted that antiphospholipid antibodies can activate endothelial cells, platelets, and neutrophils, and some patients with persistently circulating antiphospholipid antibodies can develop antiphospholipid syndrome – an acquired thromboinflammatory disease characterized by arterial, venous, and microvascular thrombotic events and obstetric complications.

Cross-sectional studies have shown that antiphospholipid antibodies are acutely present in up to 17.4% of patients with stroke or transient ischemic attack, and small cohort studies have suggested that such antibodies may be present in 1%-12% of seemingly healthy individuals. However, the impact of sex, race, and ethnicity on the prevalence of antiphospholipid antibodies and their association with atherosclerotic cardiovascular disease is not known.

The researchers conducted the current study to look at the association between antiphospholipid antibodies and future risk for atherosclerotic cardiovascular events.

They analyzed data from 2,427 participants in the population-based Dallas Heart Study who had no history of atherosclerotic cardiovascular disease or autoimmune diseases requiring immunosuppressive medications at the time of blood sampling at study entry in 2007-2009.

Eight different types of antiphospholipid antibodies were measured, and data on cardiovascular events over the next 8 years was recorded.

Results showed that 14.5% of the cohort tested positive for one of these antiphospholipid antibodies at the start of the study, with approximately one-third of those detected at a moderate or high titer.

The researchers also found that the IgA isotypes of two antiphospholipid antibodies – anticardiolipin and anti-beta-2 glycoprotein – were associated with future atherosclerotic cardiovascular events.

After adjustment for other known risk factors, individuals testing positive for the IgA isotype of anticardiolipin had an almost five times increased risk (hazard ratio, 4.92) of the primary endpoint (myocardial infarction, stroke, coronary revascularization, or cardiovascular death); while those testing positive for anti–beta₂-glycoprotein had an almost three times increased risk (HR, 2.91).

Furthermore, there was what appeared to be a dose effect. People with the highest levels of these antibodies also had the highest risk for cardiovascular events, with up to an almost 10-fold increased risk with the higher level of anticardiolipin. 

Dr. Knight said that more research into the IgA isotypes of these antiphospholipid antibodies is needed.

“Most of the mechanistic work in the antiphospholipid syndrome field has focused on IgG antiphospholipid antibodies. While we commonly find these IgA antibodies in patients with APS, the extent to which they contribute to disease has not been firmly established,” he said. “The fact that IgA was the primary hit in our unbiased screen suggests that there is more to the story and we need to better understand the implications of having these antibodies in circulation, and what specific problems they may be causing.”

Noting that antiphospholipid antibodies can form transiently after certain situations, such as infections, Dr. Knight said that further studies were needed with repeat blood testing to detect the chronic presence of the antibodies.

He added that information of venous thromboses was not available in this study and “perhaps some of the other antibodies might have stood out if we were able to analyze for different outcomes.”

This study was supported by a Pfizer Aspire Award. Dr. Knight reported receiving research funding and consulting fees from Jazz Pharmaceuticals outside the submitted work.

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

The presence of antiphospholipid antibodies is associated with an increased risk for future cardiovascular events, according to a new study.

The findings point to possible new approaches to risk stratification and the potential for new therapeutic targets in heart disease.

“In this study of the general population, we found that two antiphospholipid antibodies were associated with an increased risk of having a serious cardiovascular event over a follow-up of 8 years,” coauthor Jason Knight, MD, University of Michigan, Ann Arbor, said in an interview.

“If confirmed in further studies, these findings could be used to identify a subgroup of patients who need more careful monitoring and more aggressive risk-factor modification, and if the increased risk linked to these antibodies is high enough, it may also justify preemptive treatments such as the anticoagulants that are routinely used in antiphospholipid syndrome,” Dr. Knight said.

“The long-term vision is that we may identify some people in the general population who would benefit from treating the immune system for the prevention and treatment of cardiovascular disease instead of, or in addition to, using typical cardiovascular medications,” he added.

The study was published online in JAMA Network Open.

Individuals with autoimmune and inflammatory diseases have a greater risk for cardiovascular events than expected based on traditional cardiovascular risk factors, with mechanisms proposed to explain this risk including inflammation-mediated disruption of vascular integrity and activation of platelets and coagulation pathways, the authors explained. However, the role of autoantibodies remains unclear.

They noted that antiphospholipid antibodies can activate endothelial cells, platelets, and neutrophils, and some patients with persistently circulating antiphospholipid antibodies can develop antiphospholipid syndrome – an acquired thromboinflammatory disease characterized by arterial, venous, and microvascular thrombotic events and obstetric complications.

Cross-sectional studies have shown that antiphospholipid antibodies are acutely present in up to 17.4% of patients with stroke or transient ischemic attack, and small cohort studies have suggested that such antibodies may be present in 1%-12% of seemingly healthy individuals. However, the impact of sex, race, and ethnicity on the prevalence of antiphospholipid antibodies and their association with atherosclerotic cardiovascular disease is not known.

The researchers conducted the current study to look at the association between antiphospholipid antibodies and future risk for atherosclerotic cardiovascular events.

They analyzed data from 2,427 participants in the population-based Dallas Heart Study who had no history of atherosclerotic cardiovascular disease or autoimmune diseases requiring immunosuppressive medications at the time of blood sampling at study entry in 2007-2009.

Eight different types of antiphospholipid antibodies were measured, and data on cardiovascular events over the next 8 years was recorded.

Results showed that 14.5% of the cohort tested positive for one of these antiphospholipid antibodies at the start of the study, with approximately one-third of those detected at a moderate or high titer.

The researchers also found that the IgA isotypes of two antiphospholipid antibodies – anticardiolipin and anti-beta-2 glycoprotein – were associated with future atherosclerotic cardiovascular events.

After adjustment for other known risk factors, individuals testing positive for the IgA isotype of anticardiolipin had an almost five times increased risk (hazard ratio, 4.92) of the primary endpoint (myocardial infarction, stroke, coronary revascularization, or cardiovascular death); while those testing positive for anti–beta₂-glycoprotein had an almost three times increased risk (HR, 2.91).

Furthermore, there was what appeared to be a dose effect. People with the highest levels of these antibodies also had the highest risk for cardiovascular events, with up to an almost 10-fold increased risk with the higher level of anticardiolipin. 

Dr. Knight said that more research into the IgA isotypes of these antiphospholipid antibodies is needed.

“Most of the mechanistic work in the antiphospholipid syndrome field has focused on IgG antiphospholipid antibodies. While we commonly find these IgA antibodies in patients with APS, the extent to which they contribute to disease has not been firmly established,” he said. “The fact that IgA was the primary hit in our unbiased screen suggests that there is more to the story and we need to better understand the implications of having these antibodies in circulation, and what specific problems they may be causing.”

Noting that antiphospholipid antibodies can form transiently after certain situations, such as infections, Dr. Knight said that further studies were needed with repeat blood testing to detect the chronic presence of the antibodies.

He added that information of venous thromboses was not available in this study and “perhaps some of the other antibodies might have stood out if we were able to analyze for different outcomes.”

This study was supported by a Pfizer Aspire Award. Dr. Knight reported receiving research funding and consulting fees from Jazz Pharmaceuticals outside the submitted work.

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

NEW ORLEANS – The sociodemographic characteristics of Black and Hispanic children with systemic lupus erythematosus (SLE) appear to play a strong role in influencing the severity of disease in these patients, according to two studies presented at the Pediatric Rheumatology Symposium.

One study showed an association between multiple determinants of health and disease severity among children seen in a large Texas city, and a separate descriptive cross-sectional cohort study of predominantly Black children at two centers in Mississippi and Alabama reinforced the finding of greater severity of disease and social hardships among this racial group.

The findings from both studies supplement existing evidence that the prevalence of childhood-onset SLE is greater among Black and Hispanic children.

“Several demographic and social determinants of health parameters influenced disease severity at levels that reached statistical significance, including insurance status, race/ethnicity, referral source, PCP [primary care provider] availability, primary language, and transportation needs,” Emily Beil, MD, a pediatric rheumatologist at Texas Children’s Hospital in Houston, told attendees at the conference, which was sponsored by the American College of Rheumatology. Her team’s goal, she said, was to “better understand our patient population and social disparities that contribute to disease severity.”

Dr. Beil and her colleagues conducted a retrospective review of 136 children who had been diagnosed with childhood-onset SLE between January 2018 and May 2022 at Texas Children’s Hospital. Only children who were younger than 18 years at the time of diagnosis at Texas Children’s were included. The analysis considered demographics, clinical characteristics, insurance status, social work consultation, access to a primary care provider, transportation needs, primary language, and other parameters related to social determinants of health.

The average age of the patients was 13 years, and most were girls (82%). Just over half were Hispanic (53%), and just over a quarter were Black (26%). Half had Medicaid or participated in the Children’s Health Insurance Program (CHIP), and 1 in 10 were uninsured (10%). Half the diagnoses were made during an inpatient admission; 36% were made on the floor, and 14% were made in the intensive care unit (ICU).

The average Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 12.5, and 48.5% of patients had severe disease, indicated by a score of at least 12. Only two in three children were documented as having a primary care physician (66%), and 32% preferred a language other than English. Most of the children (80%) had a social work consult.

Black and biracial children had higher SLEDAI scores at presentation. Non-Hispanic White children were less likely to have a social work consult, compared with other racial/ethnic groups (P = .01 for both). Central nervous system involvement was most prevalent among Black patients (P = .004). Cyclophosphamide was used most often for Black and biracial patients.

Uninsured patients were most likely to be diagnosed on an inpatient floor. The highest proportion of ICU admissions was among patients insured by Medicaid (P = .034). Average SLEDAI scores were highest among uninsured patients, followed by Medicaid patients. More than half of the patients who did not have insurance lacked access to a regular primary care provider, compared with 12% of Medicaid patients and 7% of privately insured patients (P = .001). All the uninsured patients had transportation needs, which was a significantly higher rate than among those with Medicaid (13%) or private insurance (15%) (P = .001). The highest percentage of social work consults was among patients who were insured by Medicaid or were without insurance (P = .001).
 

Salient demographics and clinical features

In the second presentation, Anita Dhanrajani, MD, assistant professor of pediatrics at the University of Mississippi Medical Center in Jackson, began by noting that Alabama and Mississippi are ranked in the top 10 states for the highest poverty rate: Mississippi is No. 1, and Alabama is No. 7. Further, 40% of children in Mississippi and 29% of children in Alabama are of African American ancestry, she said.

“So, we know that this population that we’re dealing with has several high-risk factors that can lead them to have poor outcomes, and yet, we haven’t really ever characterized their clinical features or their social demographic features,” Dr. Dhanrajani told attendees. “My hope is that with this very miniscule first step, we’re able to move towards solutions to decrease health care disparities in this population.”

She presented findings regarding the first of three aims in the study, which was to describe the baseline clinical, demographic, and socioeconomic profiles of childhood lupus patients at the two centers. The two other aims were to examine genetic factors potentially linked to poor outcomes in the cohort and to assess the mental health status of the population.

The study relied on a retrospective chart review for the 17 patients at the University of Mississippi Medical Center and on Childhood Arthritis and Rheumatology Research Alliance registry data for the 19 patients at the University of Alabama at Birmingham. Most of the patients (86%) were female, Black (78%), and insured by Medicaid (64%). The average age at diagnosis was 13 years. Most (83%) also lived in a ZIP code that met the criteria for a medium-high or high Social Vulnerability Index. The children had to travel an average 75 miles to see a rheumatologist, compared with the national average of 43 miles.

At diagnosis, their average Systemic Lupus International Collaborating Clinics (SLICC) score was 8.8, their average American College of Rheumatology score was 5.2, and their average SLEDAI score was 12.1 – the latter was substantially higher than the average 3.1 score in a multiethnic Canadian cohort (the 1000 Canadian Faces of Lupus Study) with 10% Black children (P < .00001). The SLEDAI score dropped to 6.8 at 6 months and to 4 at 1 year. Nearly half (47%) had a SLICC Damage Index (SDI) greater than 0, and one-third had an SDI of 2 or greater, compared with 16% and 7%, respectively, reported in other recent studies (P < .0001 for both).

“These disparities are very difficult to investigate in terms of causal relationships and [are] likely to be very modifiable,” Coziana Ciurtin, MD, PhD, associate professor of rheumatology at University College London, told this news organization. “I think the socioeconomic status, the level of education, poverty, [type of] medical insurance, and probably genetic variants are all underpinning the presentation, damage, or disease activity being very high, and also organ involvement,” such as the greater CNS involvement seen in non-White patients.

Being mindful of these risk profiles can help doctors in asking about patients’ support at home and their families’ education, beliefs, and cultural practices, Dr. Ciurtin added. “Helping them to engage and be involved in decision-making is probably the most important” aspect of learning this information about families, she said.

Collecting this information should not be the sole responsibility of the physician, added Eve Smith, PhD, MBCHB, an academic clinical lecturer at the University of Liverpool, England, who attended the presentations. Dr. Smith noted a discussion in a work group during the previous day of the conference concerning questionnaires for screening patients regarding the need for social services and for identifying areas in which patients and their families were having difficulties.

“Obviously, if you’re going to do that, you have to have access to someone who can actually help to deal with that. Some hospitals have patient navigators that can help, for example, with a food security issue to highlight resources within the community, so it’s not all on the doctor,” Dr. Smith said. “To really make a difference in this area, it can’t just be down to the doctor. There needs to be social care, there needs to be community-based interventions and things to do about it. Doctors can help identify these patients, or maybe somebody in the [medical] team can help with that, but there needs to be an intervention. Otherwise, you’re left with this problem without a solution that you can’t do anything about.”

The researchers did not note any external funding for either study. Dr. Beil, Dr. Dhanrajani, Dr. Smith, and Dr. Ciurtin reported no relevant financial relationships.

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

NEW ORLEANS – The sociodemographic characteristics of Black and Hispanic children with systemic lupus erythematosus (SLE) appear to play a strong role in influencing the severity of disease in these patients, according to two studies presented at the Pediatric Rheumatology Symposium.

One study showed an association between multiple determinants of health and disease severity among children seen in a large Texas city, and a separate descriptive cross-sectional cohort study of predominantly Black children at two centers in Mississippi and Alabama reinforced the finding of greater severity of disease and social hardships among this racial group.

The findings from both studies supplement existing evidence that the prevalence of childhood-onset SLE is greater among Black and Hispanic children.

“Several demographic and social determinants of health parameters influenced disease severity at levels that reached statistical significance, including insurance status, race/ethnicity, referral source, PCP [primary care provider] availability, primary language, and transportation needs,” Emily Beil, MD, a pediatric rheumatologist at Texas Children’s Hospital in Houston, told attendees at the conference, which was sponsored by the American College of Rheumatology. Her team’s goal, she said, was to “better understand our patient population and social disparities that contribute to disease severity.”

Dr. Beil and her colleagues conducted a retrospective review of 136 children who had been diagnosed with childhood-onset SLE between January 2018 and May 2022 at Texas Children’s Hospital. Only children who were younger than 18 years at the time of diagnosis at Texas Children’s were included. The analysis considered demographics, clinical characteristics, insurance status, social work consultation, access to a primary care provider, transportation needs, primary language, and other parameters related to social determinants of health.

The average age of the patients was 13 years, and most were girls (82%). Just over half were Hispanic (53%), and just over a quarter were Black (26%). Half had Medicaid or participated in the Children’s Health Insurance Program (CHIP), and 1 in 10 were uninsured (10%). Half the diagnoses were made during an inpatient admission; 36% were made on the floor, and 14% were made in the intensive care unit (ICU).

The average Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 12.5, and 48.5% of patients had severe disease, indicated by a score of at least 12. Only two in three children were documented as having a primary care physician (66%), and 32% preferred a language other than English. Most of the children (80%) had a social work consult.

Black and biracial children had higher SLEDAI scores at presentation. Non-Hispanic White children were less likely to have a social work consult, compared with other racial/ethnic groups (P = .01 for both). Central nervous system involvement was most prevalent among Black patients (P = .004). Cyclophosphamide was used most often for Black and biracial patients.

Uninsured patients were most likely to be diagnosed on an inpatient floor. The highest proportion of ICU admissions was among patients insured by Medicaid (P = .034). Average SLEDAI scores were highest among uninsured patients, followed by Medicaid patients. More than half of the patients who did not have insurance lacked access to a regular primary care provider, compared with 12% of Medicaid patients and 7% of privately insured patients (P = .001). All the uninsured patients had transportation needs, which was a significantly higher rate than among those with Medicaid (13%) or private insurance (15%) (P = .001). The highest percentage of social work consults was among patients who were insured by Medicaid or were without insurance (P = .001).
 

Salient demographics and clinical features

In the second presentation, Anita Dhanrajani, MD, assistant professor of pediatrics at the University of Mississippi Medical Center in Jackson, began by noting that Alabama and Mississippi are ranked in the top 10 states for the highest poverty rate: Mississippi is No. 1, and Alabama is No. 7. Further, 40% of children in Mississippi and 29% of children in Alabama are of African American ancestry, she said.

“So, we know that this population that we’re dealing with has several high-risk factors that can lead them to have poor outcomes, and yet, we haven’t really ever characterized their clinical features or their social demographic features,” Dr. Dhanrajani told attendees. “My hope is that with this very miniscule first step, we’re able to move towards solutions to decrease health care disparities in this population.”

She presented findings regarding the first of three aims in the study, which was to describe the baseline clinical, demographic, and socioeconomic profiles of childhood lupus patients at the two centers. The two other aims were to examine genetic factors potentially linked to poor outcomes in the cohort and to assess the mental health status of the population.

The study relied on a retrospective chart review for the 17 patients at the University of Mississippi Medical Center and on Childhood Arthritis and Rheumatology Research Alliance registry data for the 19 patients at the University of Alabama at Birmingham. Most of the patients (86%) were female, Black (78%), and insured by Medicaid (64%). The average age at diagnosis was 13 years. Most (83%) also lived in a ZIP code that met the criteria for a medium-high or high Social Vulnerability Index. The children had to travel an average 75 miles to see a rheumatologist, compared with the national average of 43 miles.

At diagnosis, their average Systemic Lupus International Collaborating Clinics (SLICC) score was 8.8, their average American College of Rheumatology score was 5.2, and their average SLEDAI score was 12.1 – the latter was substantially higher than the average 3.1 score in a multiethnic Canadian cohort (the 1000 Canadian Faces of Lupus Study) with 10% Black children (P < .00001). The SLEDAI score dropped to 6.8 at 6 months and to 4 at 1 year. Nearly half (47%) had a SLICC Damage Index (SDI) greater than 0, and one-third had an SDI of 2 or greater, compared with 16% and 7%, respectively, reported in other recent studies (P < .0001 for both).

“These disparities are very difficult to investigate in terms of causal relationships and [are] likely to be very modifiable,” Coziana Ciurtin, MD, PhD, associate professor of rheumatology at University College London, told this news organization. “I think the socioeconomic status, the level of education, poverty, [type of] medical insurance, and probably genetic variants are all underpinning the presentation, damage, or disease activity being very high, and also organ involvement,” such as the greater CNS involvement seen in non-White patients.

Being mindful of these risk profiles can help doctors in asking about patients’ support at home and their families’ education, beliefs, and cultural practices, Dr. Ciurtin added. “Helping them to engage and be involved in decision-making is probably the most important” aspect of learning this information about families, she said.

Collecting this information should not be the sole responsibility of the physician, added Eve Smith, PhD, MBCHB, an academic clinical lecturer at the University of Liverpool, England, who attended the presentations. Dr. Smith noted a discussion in a work group during the previous day of the conference concerning questionnaires for screening patients regarding the need for social services and for identifying areas in which patients and their families were having difficulties.

“Obviously, if you’re going to do that, you have to have access to someone who can actually help to deal with that. Some hospitals have patient navigators that can help, for example, with a food security issue to highlight resources within the community, so it’s not all on the doctor,” Dr. Smith said. “To really make a difference in this area, it can’t just be down to the doctor. There needs to be social care, there needs to be community-based interventions and things to do about it. Doctors can help identify these patients, or maybe somebody in the [medical] team can help with that, but there needs to be an intervention. Otherwise, you’re left with this problem without a solution that you can’t do anything about.”

The researchers did not note any external funding for either study. Dr. Beil, Dr. Dhanrajani, Dr. Smith, and Dr. Ciurtin reported no relevant financial relationships.

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

NEW ORLEANS – The sociodemographic characteristics of Black and Hispanic children with systemic lupus erythematosus (SLE) appear to play a strong role in influencing the severity of disease in these patients, according to two studies presented at the Pediatric Rheumatology Symposium.

One study showed an association between multiple determinants of health and disease severity among children seen in a large Texas city, and a separate descriptive cross-sectional cohort study of predominantly Black children at two centers in Mississippi and Alabama reinforced the finding of greater severity of disease and social hardships among this racial group.

The findings from both studies supplement existing evidence that the prevalence of childhood-onset SLE is greater among Black and Hispanic children.

“Several demographic and social determinants of health parameters influenced disease severity at levels that reached statistical significance, including insurance status, race/ethnicity, referral source, PCP [primary care provider] availability, primary language, and transportation needs,” Emily Beil, MD, a pediatric rheumatologist at Texas Children’s Hospital in Houston, told attendees at the conference, which was sponsored by the American College of Rheumatology. Her team’s goal, she said, was to “better understand our patient population and social disparities that contribute to disease severity.”

Dr. Beil and her colleagues conducted a retrospective review of 136 children who had been diagnosed with childhood-onset SLE between January 2018 and May 2022 at Texas Children’s Hospital. Only children who were younger than 18 years at the time of diagnosis at Texas Children’s were included. The analysis considered demographics, clinical characteristics, insurance status, social work consultation, access to a primary care provider, transportation needs, primary language, and other parameters related to social determinants of health.

The average age of the patients was 13 years, and most were girls (82%). Just over half were Hispanic (53%), and just over a quarter were Black (26%). Half had Medicaid or participated in the Children’s Health Insurance Program (CHIP), and 1 in 10 were uninsured (10%). Half the diagnoses were made during an inpatient admission; 36% were made on the floor, and 14% were made in the intensive care unit (ICU).

The average Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 12.5, and 48.5% of patients had severe disease, indicated by a score of at least 12. Only two in three children were documented as having a primary care physician (66%), and 32% preferred a language other than English. Most of the children (80%) had a social work consult.

Black and biracial children had higher SLEDAI scores at presentation. Non-Hispanic White children were less likely to have a social work consult, compared with other racial/ethnic groups (P = .01 for both). Central nervous system involvement was most prevalent among Black patients (P = .004). Cyclophosphamide was used most often for Black and biracial patients.

Uninsured patients were most likely to be diagnosed on an inpatient floor. The highest proportion of ICU admissions was among patients insured by Medicaid (P = .034). Average SLEDAI scores were highest among uninsured patients, followed by Medicaid patients. More than half of the patients who did not have insurance lacked access to a regular primary care provider, compared with 12% of Medicaid patients and 7% of privately insured patients (P = .001). All the uninsured patients had transportation needs, which was a significantly higher rate than among those with Medicaid (13%) or private insurance (15%) (P = .001). The highest percentage of social work consults was among patients who were insured by Medicaid or were without insurance (P = .001).
 

Salient demographics and clinical features

In the second presentation, Anita Dhanrajani, MD, assistant professor of pediatrics at the University of Mississippi Medical Center in Jackson, began by noting that Alabama and Mississippi are ranked in the top 10 states for the highest poverty rate: Mississippi is No. 1, and Alabama is No. 7. Further, 40% of children in Mississippi and 29% of children in Alabama are of African American ancestry, she said.

“So, we know that this population that we’re dealing with has several high-risk factors that can lead them to have poor outcomes, and yet, we haven’t really ever characterized their clinical features or their social demographic features,” Dr. Dhanrajani told attendees. “My hope is that with this very miniscule first step, we’re able to move towards solutions to decrease health care disparities in this population.”

She presented findings regarding the first of three aims in the study, which was to describe the baseline clinical, demographic, and socioeconomic profiles of childhood lupus patients at the two centers. The two other aims were to examine genetic factors potentially linked to poor outcomes in the cohort and to assess the mental health status of the population.

The study relied on a retrospective chart review for the 17 patients at the University of Mississippi Medical Center and on Childhood Arthritis and Rheumatology Research Alliance registry data for the 19 patients at the University of Alabama at Birmingham. Most of the patients (86%) were female, Black (78%), and insured by Medicaid (64%). The average age at diagnosis was 13 years. Most (83%) also lived in a ZIP code that met the criteria for a medium-high or high Social Vulnerability Index. The children had to travel an average 75 miles to see a rheumatologist, compared with the national average of 43 miles.

At diagnosis, their average Systemic Lupus International Collaborating Clinics (SLICC) score was 8.8, their average American College of Rheumatology score was 5.2, and their average SLEDAI score was 12.1 – the latter was substantially higher than the average 3.1 score in a multiethnic Canadian cohort (the 1000 Canadian Faces of Lupus Study) with 10% Black children (P < .00001). The SLEDAI score dropped to 6.8 at 6 months and to 4 at 1 year. Nearly half (47%) had a SLICC Damage Index (SDI) greater than 0, and one-third had an SDI of 2 or greater, compared with 16% and 7%, respectively, reported in other recent studies (P < .0001 for both).

“These disparities are very difficult to investigate in terms of causal relationships and [are] likely to be very modifiable,” Coziana Ciurtin, MD, PhD, associate professor of rheumatology at University College London, told this news organization. “I think the socioeconomic status, the level of education, poverty, [type of] medical insurance, and probably genetic variants are all underpinning the presentation, damage, or disease activity being very high, and also organ involvement,” such as the greater CNS involvement seen in non-White patients.

Being mindful of these risk profiles can help doctors in asking about patients’ support at home and their families’ education, beliefs, and cultural practices, Dr. Ciurtin added. “Helping them to engage and be involved in decision-making is probably the most important” aspect of learning this information about families, she said.

Collecting this information should not be the sole responsibility of the physician, added Eve Smith, PhD, MBCHB, an academic clinical lecturer at the University of Liverpool, England, who attended the presentations. Dr. Smith noted a discussion in a work group during the previous day of the conference concerning questionnaires for screening patients regarding the need for social services and for identifying areas in which patients and their families were having difficulties.

“Obviously, if you’re going to do that, you have to have access to someone who can actually help to deal with that. Some hospitals have patient navigators that can help, for example, with a food security issue to highlight resources within the community, so it’s not all on the doctor,” Dr. Smith said. “To really make a difference in this area, it can’t just be down to the doctor. There needs to be social care, there needs to be community-based interventions and things to do about it. Doctors can help identify these patients, or maybe somebody in the [medical] team can help with that, but there needs to be an intervention. Otherwise, you’re left with this problem without a solution that you can’t do anything about.”

The researchers did not note any external funding for either study. Dr. Beil, Dr. Dhanrajani, Dr. Smith, and Dr. Ciurtin reported no relevant financial relationships.

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

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

Clinical research into lupus has long been hampered by failures of medications that initially seemed promising. Now, a coalition of drugmakers, federal regulators, and activists has come together to forge a path toward better-designed studies and – potentially – groundbreaking new drugs.

“We have an opportunity to work collaboratively in lupus to address the challenges in drug development,” Teodora Staeva, PhD, vice president and chief scientific officer of the Lupus Research Alliance, said in an interview.

The alliance held a press conference on March 29 to announce the formation of the public-private Lupus Accelerating Breakthroughs Consortium. Coalition members include several major drugmakers, lupus organizations such as the LRA, the American College of Rheumatology, the Food and Drug Administration, and other federal agencies. Academic researchers, people living with lupus, caregivers and family members, and other members of the lupus community are also on board.

As Dr. Staeva explained, research into lupus has been marked by a high rate of failure. “Often, phase 2 trial successes have not translated into phase 3 successes,” she said.

But researchers, she said, don’t tend to think this is because the drugs themselves are useless.

Instead, it appears that “trial designs are not adequate to capture meaningful readouts of the drug effects, and that may have contributed to the multiple failures,” she said.

According to her, this may because the trials aren’t yet designed to fully detect whether drugs are useful. This is difficult to accomplish since patients have so many manifestations of the disease and trial participants already take a variety of existing drugs.

“Another major limitation has been the lack of integration of the patient’s voice and needs in the drug development process,” she said. It’s also challenging to recruit patients with the most severe lupus to participate in studies, especially since the trials often last 52 weeks.

The new coalition will not directly develop or favor specific drugs. Instead, it will focus on clinical research priorities. “It’s all open and collaborative,” Dr. Staeva explained, and a patient council will provide input. “We have a unique opportunity to bring the voice of people [living with lupus] to the table for the first time and be able to integrate their needs and priorities into the infrastructure.”

The new coalition was inspired by existing public-private partnerships such as the Kidney Health Initiative, she said. That initiative was founded in 2012 by the FDA and the American Society of Nephrology and has dozens of members, including multiple drugmakers and medical societies.

The leadership of the Lupus ABC coalition will include three nonvoting members from the FDA. They’ll offer guidance, Dr. Staeva said. At the press conference, Albert T. Roy, president and CEO of the LRA, said drug companies will appreciate the opportunity to speak with FDA representatives “in a space that is not competitive with respect to intellectual property or anything like that.”

The coalition will meet later in spring 2023, Dr. Staeva said. She hopes it will launch a couple of projects by the end of 2023 and be able to release preliminary results by the end of 2024.

One challenge will be figuring out how to stratify trial subjects so drug studies will more easily detect medications that may work in smaller populations of patients, Hoang Nguyen, PhD, director of scientific partnerships at the LRA, said in an interview. “Now we lump [patients] all together, and that’s not the optimal way to test drugs on patients who have a lot of differences.”

According to Dr. Staeva, the LRA funded the development of the coalition, and drugmakers will primarily provide financial support going forward. The pharmaceutical company members of the coalition are Biogen, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Merck, and Takeda.

Dr. Staeva, Dr. Nguyen, and Mr. Roy have no disclosures.

Clinical research into lupus has long been hampered by failures of medications that initially seemed promising. Now, a coalition of drugmakers, federal regulators, and activists has come together to forge a path toward better-designed studies and – potentially – groundbreaking new drugs.

“We have an opportunity to work collaboratively in lupus to address the challenges in drug development,” Teodora Staeva, PhD, vice president and chief scientific officer of the Lupus Research Alliance, said in an interview.

The alliance held a press conference on March 29 to announce the formation of the public-private Lupus Accelerating Breakthroughs Consortium. Coalition members include several major drugmakers, lupus organizations such as the LRA, the American College of Rheumatology, the Food and Drug Administration, and other federal agencies. Academic researchers, people living with lupus, caregivers and family members, and other members of the lupus community are also on board.

As Dr. Staeva explained, research into lupus has been marked by a high rate of failure. “Often, phase 2 trial successes have not translated into phase 3 successes,” she said.

But researchers, she said, don’t tend to think this is because the drugs themselves are useless.

Instead, it appears that “trial designs are not adequate to capture meaningful readouts of the drug effects, and that may have contributed to the multiple failures,” she said.

According to her, this may because the trials aren’t yet designed to fully detect whether drugs are useful. This is difficult to accomplish since patients have so many manifestations of the disease and trial participants already take a variety of existing drugs.

“Another major limitation has been the lack of integration of the patient’s voice and needs in the drug development process,” she said. It’s also challenging to recruit patients with the most severe lupus to participate in studies, especially since the trials often last 52 weeks.

The new coalition will not directly develop or favor specific drugs. Instead, it will focus on clinical research priorities. “It’s all open and collaborative,” Dr. Staeva explained, and a patient council will provide input. “We have a unique opportunity to bring the voice of people [living with lupus] to the table for the first time and be able to integrate their needs and priorities into the infrastructure.”

The new coalition was inspired by existing public-private partnerships such as the Kidney Health Initiative, she said. That initiative was founded in 2012 by the FDA and the American Society of Nephrology and has dozens of members, including multiple drugmakers and medical societies.

The leadership of the Lupus ABC coalition will include three nonvoting members from the FDA. They’ll offer guidance, Dr. Staeva said. At the press conference, Albert T. Roy, president and CEO of the LRA, said drug companies will appreciate the opportunity to speak with FDA representatives “in a space that is not competitive with respect to intellectual property or anything like that.”

The coalition will meet later in spring 2023, Dr. Staeva said. She hopes it will launch a couple of projects by the end of 2023 and be able to release preliminary results by the end of 2024.

One challenge will be figuring out how to stratify trial subjects so drug studies will more easily detect medications that may work in smaller populations of patients, Hoang Nguyen, PhD, director of scientific partnerships at the LRA, said in an interview. “Now we lump [patients] all together, and that’s not the optimal way to test drugs on patients who have a lot of differences.”

According to Dr. Staeva, the LRA funded the development of the coalition, and drugmakers will primarily provide financial support going forward. The pharmaceutical company members of the coalition are Biogen, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Merck, and Takeda.

Dr. Staeva, Dr. Nguyen, and Mr. Roy have no disclosures.

Clinical research into lupus has long been hampered by failures of medications that initially seemed promising. Now, a coalition of drugmakers, federal regulators, and activists has come together to forge a path toward better-designed studies and – potentially – groundbreaking new drugs.

“We have an opportunity to work collaboratively in lupus to address the challenges in drug development,” Teodora Staeva, PhD, vice president and chief scientific officer of the Lupus Research Alliance, said in an interview.

The alliance held a press conference on March 29 to announce the formation of the public-private Lupus Accelerating Breakthroughs Consortium. Coalition members include several major drugmakers, lupus organizations such as the LRA, the American College of Rheumatology, the Food and Drug Administration, and other federal agencies. Academic researchers, people living with lupus, caregivers and family members, and other members of the lupus community are also on board.

As Dr. Staeva explained, research into lupus has been marked by a high rate of failure. “Often, phase 2 trial successes have not translated into phase 3 successes,” she said.

But researchers, she said, don’t tend to think this is because the drugs themselves are useless.

Instead, it appears that “trial designs are not adequate to capture meaningful readouts of the drug effects, and that may have contributed to the multiple failures,” she said.

According to her, this may because the trials aren’t yet designed to fully detect whether drugs are useful. This is difficult to accomplish since patients have so many manifestations of the disease and trial participants already take a variety of existing drugs.

“Another major limitation has been the lack of integration of the patient’s voice and needs in the drug development process,” she said. It’s also challenging to recruit patients with the most severe lupus to participate in studies, especially since the trials often last 52 weeks.

The new coalition will not directly develop or favor specific drugs. Instead, it will focus on clinical research priorities. “It’s all open and collaborative,” Dr. Staeva explained, and a patient council will provide input. “We have a unique opportunity to bring the voice of people [living with lupus] to the table for the first time and be able to integrate their needs and priorities into the infrastructure.”

The new coalition was inspired by existing public-private partnerships such as the Kidney Health Initiative, she said. That initiative was founded in 2012 by the FDA and the American Society of Nephrology and has dozens of members, including multiple drugmakers and medical societies.

The leadership of the Lupus ABC coalition will include three nonvoting members from the FDA. They’ll offer guidance, Dr. Staeva said. At the press conference, Albert T. Roy, president and CEO of the LRA, said drug companies will appreciate the opportunity to speak with FDA representatives “in a space that is not competitive with respect to intellectual property or anything like that.”

The coalition will meet later in spring 2023, Dr. Staeva said. She hopes it will launch a couple of projects by the end of 2023 and be able to release preliminary results by the end of 2024.

One challenge will be figuring out how to stratify trial subjects so drug studies will more easily detect medications that may work in smaller populations of patients, Hoang Nguyen, PhD, director of scientific partnerships at the LRA, said in an interview. “Now we lump [patients] all together, and that’s not the optimal way to test drugs on patients who have a lot of differences.”

According to Dr. Staeva, the LRA funded the development of the coalition, and drugmakers will primarily provide financial support going forward. The pharmaceutical company members of the coalition are Biogen, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Merck, and Takeda.

Dr. Staeva, Dr. Nguyen, and Mr. Roy have no disclosures.

Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.

“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”

He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”

The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.

It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.

Kaiser Permanente

Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
 

Insurance often drives the conversation

The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.

Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.

Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.

Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”

However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.

This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.

But not all physicians are quick to prescribe biosimilars.

Julie Miller Photography

Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”

Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
 

Conversations about cost

Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.

If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.

Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.

Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”

Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.

“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.

Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”

For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.

Biosimilars 101: Familiarizing patients

Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.

Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.

Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 

rubberball/Getty Images

As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.

When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.

Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.

In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
 

A village approach to education

When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.

The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar. 

This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”

Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”

Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.

No consensus on interchangeability

Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.

If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.

The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.

In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).

“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.

Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”

Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.

“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
 

Resources for physicians, patients

The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.

The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.

Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.

“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.

Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.

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

Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.

“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”

He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”

The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.

It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.

Kaiser Permanente

Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
 

Insurance often drives the conversation

The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.

Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.

Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.

Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”

However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.

This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.

But not all physicians are quick to prescribe biosimilars.

Julie Miller Photography

Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”

Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
 

Conversations about cost

Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.

If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.

Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.

Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”

Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.

“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.

Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”

For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.

Biosimilars 101: Familiarizing patients

Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.

Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.

Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 

rubberball/Getty Images

As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.

When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.

Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.

In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
 

A village approach to education

When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.

The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar. 

This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”

Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”

Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.

No consensus on interchangeability

Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.

If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.

The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.

In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).

“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.

Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”

Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.

“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
 

Resources for physicians, patients

The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.

The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.

Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.

“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.

Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.

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

Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.

“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”

He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”

The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.

It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.

Kaiser Permanente

Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
 

Insurance often drives the conversation

The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.

Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.

Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.

Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”

However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.

This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.

But not all physicians are quick to prescribe biosimilars.

Julie Miller Photography

Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”

Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
 

Conversations about cost

Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.

If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.

Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.

Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”

Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.

“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.

Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”

For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.

Biosimilars 101: Familiarizing patients

Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.

Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.

Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 

rubberball/Getty Images

As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.

When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.

Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.

In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
 

A village approach to education

When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.

The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar. 

This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”

Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”

Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.

No consensus on interchangeability

Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.

If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.

The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.

In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).

“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.

Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”

Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.

“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
 

Resources for physicians, patients

The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.

The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.

Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.

“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.

Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.

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

DENVER – Adding therapies such as acupuncture, electrophysical stimulation, or other interventions to standard exercise therapy does not appear to offer much benefit in pain relief or physical function for patients with knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress. The findings were also published in the Cochrane Database of Systematic Reviews in October 2022.

“The results do not support the use of adjunctive therapies when we add them to exercise for pain, physical function, or quality of life, when compared against placebo, adjunctive therapy, and exercise,” Helen P. French, PhD, told attendees at the meeting sponsored by the Osteoarthritis Research Society International. The findings were similar for pain and physical function when comparing adjunctive therapies with exercise against exercise alone, said Dr. French, an associate professor in physiotherapy at the Royal College of Surgeons, Dublin, except that patients using adjunctive therapies reported feeling greater improvement in their global assessments.

Exercise is recommended as a core treatment for osteoarthritis, but some patients or clinicians may be interested in supplementing that therapy with acupuncture, heat therapy, electromagnetic fields, transcutaneous electrical nerve stimulation, braces/orthotics, and other interventions. Various Cochrane Reviews of the evidence exist for these interventions in treating chronic pain in general but not for their use as adjunctive therapies in addition to exercise for osteoarthritis pain.

Researchers therefore assessed the evidence for improvement in pain, physical function, and quality of life for two sets of comparisons: adjunctive therapies plus exercise versus exercise alone, and adjunctive therapies with exercise versus placebo adjunctive therapy with exercise. The review excluded studies looking at medications or supplements.

Pain was assessed with the Numeric Pain Rating Scale (NPRS, 0-10), with an improvement of at least 2 points (15% improvement) representing the minimum clinically important difference (MCID). Physical function was assessed with the Western Ontario and McMaster Universities Arthritis Index (WOMAC, 0-68), with 6 points (15%) considered the MCID, and quality of life was assessed with the SF-36 (0-100), with 6 points (12%) as the MCID.

The researchers identified trials on knee osteoarthritis that included an overall 6,508 participants with an average age ranging from 52 to 83 years. A total of 36 studies evaluated electrophysical agents. Another seven looked at manual therapies; four looked at acupuncture/dry needling or taping; three looked at psychological, dietary, or “whole body vibration” therapies; and two evaluated spa or peloid therapy. Only one trial evaluated foot insoles.

Nearly all the studies (98%) assessed pain, and most (87%) assessed physical function. Only about one in five (21%) assessed quality of life. The improvement in pain from adding adjunctive therapies to exercise, compared with placebo therapies plus exercise, was 0.77 points, or just under a 10% improvement, which fell short of the 15% MCID. Physical function improvement similarly fell short, with an average improvement of 5 points (12%).

In comparisons of exercise plus adjunctive therapies against exercise alone, the improvement from the additional interventions was even lower. Pain improvement was 0.41 points (7%), and physical function improvement was 2.8 points (9%). However, patients’ perceptions told a different story: 37% more patients who were using an adjunctive therapy reported feeling that the therapies were successful, compared with patients undergoing exercise therapy alone.

Adverse events were poorly reported in the trials, with only 10 trials reporting them at all, and the researchers found no significant difference in adverse events among the studies reporting them. The most common adverse events were increased pain in the joint with the osteoarthritis, pain elsewhere, or swelling and inflammation. It’s unclear, however, whether the pain, swelling, and inflammation were related to the interventions and how serious these effects might have been.

Michelle Hall, PhD, an associate professor in the department of physiotherapy at the University of Melbourne, comoderated the session with this presentation and found it interesting that more than one-third of patients perceived that they did better with the additional therapies even though improvement didn’t bear out in their pain or physical function assessments.

“But the other part of that was that the studies were of poor quality, so we can’t say with confidence, ‘Don’t do this therapy because it’s not going to work,’ ” Dr. Hall said in an interview. She said she personally would probably discourage patients from those therapies, “but I don’t think the evidence is there for everybody to do that,” she added.

Martin Van Der Esch, PhD, of Reade Centre of Rehabilitation and Rheumatology in Amsterdam, also comoderated the discussion and had more concerns about the use of adjunctive therapies in light of the study’s findings. He said in an interview that he tended to believe the patients’ overall self-reported improvement is likely a placebo effect, and he sees potential harm in that effect. If the pain is not truly decreasing as patients continue using those therapies, then the pain may become a more stable part of the nervous system, “so I think they need to do an intervention which really has evidence in reducing pain, an active approach that means exercising in the right way,” Dr. Van Der Esch said. If patients are undergoing therapy whose primary benefit is a placebo effect, “the pain will prolong and become more fixed in the nervous system,” shifting the patients toward greater risk of the pain becoming chronic, he said.

“I want to emphasize that we have an ethical role to our management, and it’s not ethical to give treatments which have no response and no pain relief except that the patient or the professional believes it will have an effect,” Dr. Van Der Esch said.

The research did not involve outside funding. Dr. French, Dr. Hall, and Dr. Van Der Esch reported having no relevant financial relationships.

DENVER – Adding therapies such as acupuncture, electrophysical stimulation, or other interventions to standard exercise therapy does not appear to offer much benefit in pain relief or physical function for patients with knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress. The findings were also published in the Cochrane Database of Systematic Reviews in October 2022.

“The results do not support the use of adjunctive therapies when we add them to exercise for pain, physical function, or quality of life, when compared against placebo, adjunctive therapy, and exercise,” Helen P. French, PhD, told attendees at the meeting sponsored by the Osteoarthritis Research Society International. The findings were similar for pain and physical function when comparing adjunctive therapies with exercise against exercise alone, said Dr. French, an associate professor in physiotherapy at the Royal College of Surgeons, Dublin, except that patients using adjunctive therapies reported feeling greater improvement in their global assessments.

Exercise is recommended as a core treatment for osteoarthritis, but some patients or clinicians may be interested in supplementing that therapy with acupuncture, heat therapy, electromagnetic fields, transcutaneous electrical nerve stimulation, braces/orthotics, and other interventions. Various Cochrane Reviews of the evidence exist for these interventions in treating chronic pain in general but not for their use as adjunctive therapies in addition to exercise for osteoarthritis pain.

Researchers therefore assessed the evidence for improvement in pain, physical function, and quality of life for two sets of comparisons: adjunctive therapies plus exercise versus exercise alone, and adjunctive therapies with exercise versus placebo adjunctive therapy with exercise. The review excluded studies looking at medications or supplements.

Pain was assessed with the Numeric Pain Rating Scale (NPRS, 0-10), with an improvement of at least 2 points (15% improvement) representing the minimum clinically important difference (MCID). Physical function was assessed with the Western Ontario and McMaster Universities Arthritis Index (WOMAC, 0-68), with 6 points (15%) considered the MCID, and quality of life was assessed with the SF-36 (0-100), with 6 points (12%) as the MCID.

The researchers identified trials on knee osteoarthritis that included an overall 6,508 participants with an average age ranging from 52 to 83 years. A total of 36 studies evaluated electrophysical agents. Another seven looked at manual therapies; four looked at acupuncture/dry needling or taping; three looked at psychological, dietary, or “whole body vibration” therapies; and two evaluated spa or peloid therapy. Only one trial evaluated foot insoles.

Nearly all the studies (98%) assessed pain, and most (87%) assessed physical function. Only about one in five (21%) assessed quality of life. The improvement in pain from adding adjunctive therapies to exercise, compared with placebo therapies plus exercise, was 0.77 points, or just under a 10% improvement, which fell short of the 15% MCID. Physical function improvement similarly fell short, with an average improvement of 5 points (12%).

In comparisons of exercise plus adjunctive therapies against exercise alone, the improvement from the additional interventions was even lower. Pain improvement was 0.41 points (7%), and physical function improvement was 2.8 points (9%). However, patients’ perceptions told a different story: 37% more patients who were using an adjunctive therapy reported feeling that the therapies were successful, compared with patients undergoing exercise therapy alone.

Adverse events were poorly reported in the trials, with only 10 trials reporting them at all, and the researchers found no significant difference in adverse events among the studies reporting them. The most common adverse events were increased pain in the joint with the osteoarthritis, pain elsewhere, or swelling and inflammation. It’s unclear, however, whether the pain, swelling, and inflammation were related to the interventions and how serious these effects might have been.

Michelle Hall, PhD, an associate professor in the department of physiotherapy at the University of Melbourne, comoderated the session with this presentation and found it interesting that more than one-third of patients perceived that they did better with the additional therapies even though improvement didn’t bear out in their pain or physical function assessments.

“But the other part of that was that the studies were of poor quality, so we can’t say with confidence, ‘Don’t do this therapy because it’s not going to work,’ ” Dr. Hall said in an interview. She said she personally would probably discourage patients from those therapies, “but I don’t think the evidence is there for everybody to do that,” she added.

Martin Van Der Esch, PhD, of Reade Centre of Rehabilitation and Rheumatology in Amsterdam, also comoderated the discussion and had more concerns about the use of adjunctive therapies in light of the study’s findings. He said in an interview that he tended to believe the patients’ overall self-reported improvement is likely a placebo effect, and he sees potential harm in that effect. If the pain is not truly decreasing as patients continue using those therapies, then the pain may become a more stable part of the nervous system, “so I think they need to do an intervention which really has evidence in reducing pain, an active approach that means exercising in the right way,” Dr. Van Der Esch said. If patients are undergoing therapy whose primary benefit is a placebo effect, “the pain will prolong and become more fixed in the nervous system,” shifting the patients toward greater risk of the pain becoming chronic, he said.

“I want to emphasize that we have an ethical role to our management, and it’s not ethical to give treatments which have no response and no pain relief except that the patient or the professional believes it will have an effect,” Dr. Van Der Esch said.

The research did not involve outside funding. Dr. French, Dr. Hall, and Dr. Van Der Esch reported having no relevant financial relationships.

DENVER – Adding therapies such as acupuncture, electrophysical stimulation, or other interventions to standard exercise therapy does not appear to offer much benefit in pain relief or physical function for patients with knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress. The findings were also published in the Cochrane Database of Systematic Reviews in October 2022.

“The results do not support the use of adjunctive therapies when we add them to exercise for pain, physical function, or quality of life, when compared against placebo, adjunctive therapy, and exercise,” Helen P. French, PhD, told attendees at the meeting sponsored by the Osteoarthritis Research Society International. The findings were similar for pain and physical function when comparing adjunctive therapies with exercise against exercise alone, said Dr. French, an associate professor in physiotherapy at the Royal College of Surgeons, Dublin, except that patients using adjunctive therapies reported feeling greater improvement in their global assessments.

Exercise is recommended as a core treatment for osteoarthritis, but some patients or clinicians may be interested in supplementing that therapy with acupuncture, heat therapy, electromagnetic fields, transcutaneous electrical nerve stimulation, braces/orthotics, and other interventions. Various Cochrane Reviews of the evidence exist for these interventions in treating chronic pain in general but not for their use as adjunctive therapies in addition to exercise for osteoarthritis pain.

Researchers therefore assessed the evidence for improvement in pain, physical function, and quality of life for two sets of comparisons: adjunctive therapies plus exercise versus exercise alone, and adjunctive therapies with exercise versus placebo adjunctive therapy with exercise. The review excluded studies looking at medications or supplements.

Pain was assessed with the Numeric Pain Rating Scale (NPRS, 0-10), with an improvement of at least 2 points (15% improvement) representing the minimum clinically important difference (MCID). Physical function was assessed with the Western Ontario and McMaster Universities Arthritis Index (WOMAC, 0-68), with 6 points (15%) considered the MCID, and quality of life was assessed with the SF-36 (0-100), with 6 points (12%) as the MCID.

The researchers identified trials on knee osteoarthritis that included an overall 6,508 participants with an average age ranging from 52 to 83 years. A total of 36 studies evaluated electrophysical agents. Another seven looked at manual therapies; four looked at acupuncture/dry needling or taping; three looked at psychological, dietary, or “whole body vibration” therapies; and two evaluated spa or peloid therapy. Only one trial evaluated foot insoles.

Nearly all the studies (98%) assessed pain, and most (87%) assessed physical function. Only about one in five (21%) assessed quality of life. The improvement in pain from adding adjunctive therapies to exercise, compared with placebo therapies plus exercise, was 0.77 points, or just under a 10% improvement, which fell short of the 15% MCID. Physical function improvement similarly fell short, with an average improvement of 5 points (12%).

In comparisons of exercise plus adjunctive therapies against exercise alone, the improvement from the additional interventions was even lower. Pain improvement was 0.41 points (7%), and physical function improvement was 2.8 points (9%). However, patients’ perceptions told a different story: 37% more patients who were using an adjunctive therapy reported feeling that the therapies were successful, compared with patients undergoing exercise therapy alone.

Adverse events were poorly reported in the trials, with only 10 trials reporting them at all, and the researchers found no significant difference in adverse events among the studies reporting them. The most common adverse events were increased pain in the joint with the osteoarthritis, pain elsewhere, or swelling and inflammation. It’s unclear, however, whether the pain, swelling, and inflammation were related to the interventions and how serious these effects might have been.

Michelle Hall, PhD, an associate professor in the department of physiotherapy at the University of Melbourne, comoderated the session with this presentation and found it interesting that more than one-third of patients perceived that they did better with the additional therapies even though improvement didn’t bear out in their pain or physical function assessments.

“But the other part of that was that the studies were of poor quality, so we can’t say with confidence, ‘Don’t do this therapy because it’s not going to work,’ ” Dr. Hall said in an interview. She said she personally would probably discourage patients from those therapies, “but I don’t think the evidence is there for everybody to do that,” she added.

Martin Van Der Esch, PhD, of Reade Centre of Rehabilitation and Rheumatology in Amsterdam, also comoderated the discussion and had more concerns about the use of adjunctive therapies in light of the study’s findings. He said in an interview that he tended to believe the patients’ overall self-reported improvement is likely a placebo effect, and he sees potential harm in that effect. If the pain is not truly decreasing as patients continue using those therapies, then the pain may become a more stable part of the nervous system, “so I think they need to do an intervention which really has evidence in reducing pain, an active approach that means exercising in the right way,” Dr. Van Der Esch said. If patients are undergoing therapy whose primary benefit is a placebo effect, “the pain will prolong and become more fixed in the nervous system,” shifting the patients toward greater risk of the pain becoming chronic, he said.

“I want to emphasize that we have an ethical role to our management, and it’s not ethical to give treatments which have no response and no pain relief except that the patient or the professional believes it will have an effect,” Dr. Van Der Esch said.

The research did not involve outside funding. Dr. French, Dr. Hall, and Dr. Van Der Esch reported having no relevant financial relationships.

DENVER – Using antidepressants to treat osteoarthritis pain can benefit some individuals but appears to have a clinically unimportant reduction in pain when looking at all patients who have tried them, according to a study presented at the OARSI 2023 World Congress. The review was also published in the Cochrane Database of Systematic Reviews in October 2022.

In terms of implications for clinical practice, the findings “seem to suggest there is a subgroup that is more likely to respond to antidepressants,” Anita Wluka, PhD, MBBS, a professor in the School of Public Health and Preventive Medicine at Monash University in Melbourne, told attendees. The findings also raise an important research question: “How can we identify the patient phenotype likely to benefit so we can [minimize the] risk of those adverse events and effects?”

Osteoarthritis pain is heterogeneous, and an estimated 30% of the pain is neuropathic-like, likely including central and peripheral sensitization, Dr. Wluka said. Given that antidepressants affect multiple sites along these pathways, multiple organizations have issued a conditional recommendation for duloxetine in their osteoarthritis guidelines, including OARSI, the European Alliance of Associations for Rheumatology, and the American College of Rheumatology.

The Cochrane Collaboration therefore conducted a systematic review and meta-analysis of research on the benefits and harms of using antidepressants to treat symptomatic knee and hip osteoarthritis. The review included studies through January 2021 whose participants had knee and/or hip osteoarthritis and which compared antidepressant therapy with placebo or another intervention for at least 6 weeks. The authors looked at seven outcomes: overall pain on a 0-10 scale, clinical response (at least a 50% reduction in 24‐hour mean pain), physical function using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life using the EQ-5D, the proportion of participants withdrawing because of adverse events, the proportion who experienced any adverse events, and the proportion who experienced serious adverse events.

The researchers considered a change on the pain scale of 0.5-1 points to be “slight to small,” a difference above 1 up to 2 to be “moderate,” and a difference greater than 2 points to be “large.” In assessing quality of life function on a scale of 0-100, a slight to small difference was 5-10, a moderate difference was 11-20, and a large difference was above 20.

Of the 18 articles the researchers identified for qualitative synthesis, 9 met the criteria for qualitative synthesis in the meta-analysis, including 7 studies only on the knee and 2 that included the knees and hips. All nine studies compared antidepressants with placebo, with or without NSAIDs. Most focused on serotonin and norepinephrine reuptake inhibitors (SNRIs) – six studies on duloxetine and one on milnacipran – while one included fluvoxamine and one included nortriptyline.

The trials included a combined 2,122 participants who were predominantly female with an average age range of 54-66. Trials ranged from 8 to 16 weeks. Five of the trials carried risk of attrition and reporting bias, and only one trial had low risk of bias across all domains.

In five trials with SNRIs and one trial with tricyclics (nortriptyline) totaling 1,904 participants, 45% of those receiving antidepressants had a clinical response, compared with 29% of patients who received placebo (risk ratio, 1.55; 95% CI, 1.31-1.92). This absolute improvement in pain occurred in 16% more participants taking antidepressants, giving a number needed to treat (NNT) of 6. Average improvement in WOMAC physical function was 10.5 points with placebo and 16.2 points with antidepressants, indicating a “small, clinically unimportant response,” the researchers concluded.

Withdrawals because of adverse events included 11% of the antidepressant group and 5% of the placebo group (RR, 2.15; 95% CI, 1.56-2.87), putting the NNT for a harmful outcome at 17.

For all nine trials together, however, the mean reduction in pain from antidepressants was 2.3 points, compared with 1.7 points with placebo, a statistically significant but ”clinically unimportant improvement,” the researchers concluded. Adverse events occurred in 64% of the antidepressant group, compared with 49% of the placebo group (RR, 1.27; 95% CI, 1.15-1.41), which put the NNT for a harmful outcome at 7. No significant difference in serious adverse events occurred between the groups.

The analysis was limited by the low number of trials, most of which were sponsored by industry and most of which used duloxetine. Further, few of the studies enrolled patients with osteoarthritis of the hip, none assessed medium- or long-term effects, and none stratified the participants for different types of pain (neuropathic-like or central or peripheral pain sensitization).

“My general impression is that there was a statistically significant difference found in favor of duloxetine and the antidepressants,” David J. Hunter, MBBS, PhD, MSc, of the University of Sydney, said after the presentation. “There is a real risk of harm, which I think is important to take into consideration, but at least for me as a clinician and in advising other clinicians, it’s one tool in our armamentarium. I think it’s really important to allow patients to make an informed decision about the potential benefit, the real risk of harm, and the fact that it is quite useful in some patients, and I use it in my clinical practice.”

Jeffrey N. Katz, MD, MS, of Brigham and Women’s Hospital in Boston, said he uses antidepressants in the same way in his practice and that other types of medications, such as TNF inhibitors, also carry risk of harm that may exceed that of antidepressants.

“I’ve had lots of people start duloxetine, and if they stop it, it’s usually because they just don’t tolerate it very well,” Dr. Katz said.

“We don’t want to throw too many things away,” Dr. Hunter added. “Our patients don’t necessarily have a lot of choices here from a pharmacologic perspective, so I think it’s one of those options that I want to keep in my tool kit, and that’s not necessarily going to change.”

The research did not involve outside funding, and Dr. Wluka reported having no industry disclosures. Disclosure information was unavailable for Dr. Katz and Dr. Hunter. The Congress was sponsored by the Osteoarthritis Research Society International.

DENVER – Using antidepressants to treat osteoarthritis pain can benefit some individuals but appears to have a clinically unimportant reduction in pain when looking at all patients who have tried them, according to a study presented at the OARSI 2023 World Congress. The review was also published in the Cochrane Database of Systematic Reviews in October 2022.

In terms of implications for clinical practice, the findings “seem to suggest there is a subgroup that is more likely to respond to antidepressants,” Anita Wluka, PhD, MBBS, a professor in the School of Public Health and Preventive Medicine at Monash University in Melbourne, told attendees. The findings also raise an important research question: “How can we identify the patient phenotype likely to benefit so we can [minimize the] risk of those adverse events and effects?”

Osteoarthritis pain is heterogeneous, and an estimated 30% of the pain is neuropathic-like, likely including central and peripheral sensitization, Dr. Wluka said. Given that antidepressants affect multiple sites along these pathways, multiple organizations have issued a conditional recommendation for duloxetine in their osteoarthritis guidelines, including OARSI, the European Alliance of Associations for Rheumatology, and the American College of Rheumatology.

The Cochrane Collaboration therefore conducted a systematic review and meta-analysis of research on the benefits and harms of using antidepressants to treat symptomatic knee and hip osteoarthritis. The review included studies through January 2021 whose participants had knee and/or hip osteoarthritis and which compared antidepressant therapy with placebo or another intervention for at least 6 weeks. The authors looked at seven outcomes: overall pain on a 0-10 scale, clinical response (at least a 50% reduction in 24‐hour mean pain), physical function using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life using the EQ-5D, the proportion of participants withdrawing because of adverse events, the proportion who experienced any adverse events, and the proportion who experienced serious adverse events.

The researchers considered a change on the pain scale of 0.5-1 points to be “slight to small,” a difference above 1 up to 2 to be “moderate,” and a difference greater than 2 points to be “large.” In assessing quality of life function on a scale of 0-100, a slight to small difference was 5-10, a moderate difference was 11-20, and a large difference was above 20.

Of the 18 articles the researchers identified for qualitative synthesis, 9 met the criteria for qualitative synthesis in the meta-analysis, including 7 studies only on the knee and 2 that included the knees and hips. All nine studies compared antidepressants with placebo, with or without NSAIDs. Most focused on serotonin and norepinephrine reuptake inhibitors (SNRIs) – six studies on duloxetine and one on milnacipran – while one included fluvoxamine and one included nortriptyline.

The trials included a combined 2,122 participants who were predominantly female with an average age range of 54-66. Trials ranged from 8 to 16 weeks. Five of the trials carried risk of attrition and reporting bias, and only one trial had low risk of bias across all domains.

In five trials with SNRIs and one trial with tricyclics (nortriptyline) totaling 1,904 participants, 45% of those receiving antidepressants had a clinical response, compared with 29% of patients who received placebo (risk ratio, 1.55; 95% CI, 1.31-1.92). This absolute improvement in pain occurred in 16% more participants taking antidepressants, giving a number needed to treat (NNT) of 6. Average improvement in WOMAC physical function was 10.5 points with placebo and 16.2 points with antidepressants, indicating a “small, clinically unimportant response,” the researchers concluded.

Withdrawals because of adverse events included 11% of the antidepressant group and 5% of the placebo group (RR, 2.15; 95% CI, 1.56-2.87), putting the NNT for a harmful outcome at 17.

For all nine trials together, however, the mean reduction in pain from antidepressants was 2.3 points, compared with 1.7 points with placebo, a statistically significant but ”clinically unimportant improvement,” the researchers concluded. Adverse events occurred in 64% of the antidepressant group, compared with 49% of the placebo group (RR, 1.27; 95% CI, 1.15-1.41), which put the NNT for a harmful outcome at 7. No significant difference in serious adverse events occurred between the groups.

The analysis was limited by the low number of trials, most of which were sponsored by industry and most of which used duloxetine. Further, few of the studies enrolled patients with osteoarthritis of the hip, none assessed medium- or long-term effects, and none stratified the participants for different types of pain (neuropathic-like or central or peripheral pain sensitization).

“My general impression is that there was a statistically significant difference found in favor of duloxetine and the antidepressants,” David J. Hunter, MBBS, PhD, MSc, of the University of Sydney, said after the presentation. “There is a real risk of harm, which I think is important to take into consideration, but at least for me as a clinician and in advising other clinicians, it’s one tool in our armamentarium. I think it’s really important to allow patients to make an informed decision about the potential benefit, the real risk of harm, and the fact that it is quite useful in some patients, and I use it in my clinical practice.”

Jeffrey N. Katz, MD, MS, of Brigham and Women’s Hospital in Boston, said he uses antidepressants in the same way in his practice and that other types of medications, such as TNF inhibitors, also carry risk of harm that may exceed that of antidepressants.

“I’ve had lots of people start duloxetine, and if they stop it, it’s usually because they just don’t tolerate it very well,” Dr. Katz said.

“We don’t want to throw too many things away,” Dr. Hunter added. “Our patients don’t necessarily have a lot of choices here from a pharmacologic perspective, so I think it’s one of those options that I want to keep in my tool kit, and that’s not necessarily going to change.”

The research did not involve outside funding, and Dr. Wluka reported having no industry disclosures. Disclosure information was unavailable for Dr. Katz and Dr. Hunter. The Congress was sponsored by the Osteoarthritis Research Society International.

DENVER – Using antidepressants to treat osteoarthritis pain can benefit some individuals but appears to have a clinically unimportant reduction in pain when looking at all patients who have tried them, according to a study presented at the OARSI 2023 World Congress. The review was also published in the Cochrane Database of Systematic Reviews in October 2022.

In terms of implications for clinical practice, the findings “seem to suggest there is a subgroup that is more likely to respond to antidepressants,” Anita Wluka, PhD, MBBS, a professor in the School of Public Health and Preventive Medicine at Monash University in Melbourne, told attendees. The findings also raise an important research question: “How can we identify the patient phenotype likely to benefit so we can [minimize the] risk of those adverse events and effects?”

Osteoarthritis pain is heterogeneous, and an estimated 30% of the pain is neuropathic-like, likely including central and peripheral sensitization, Dr. Wluka said. Given that antidepressants affect multiple sites along these pathways, multiple organizations have issued a conditional recommendation for duloxetine in their osteoarthritis guidelines, including OARSI, the European Alliance of Associations for Rheumatology, and the American College of Rheumatology.

The Cochrane Collaboration therefore conducted a systematic review and meta-analysis of research on the benefits and harms of using antidepressants to treat symptomatic knee and hip osteoarthritis. The review included studies through January 2021 whose participants had knee and/or hip osteoarthritis and which compared antidepressant therapy with placebo or another intervention for at least 6 weeks. The authors looked at seven outcomes: overall pain on a 0-10 scale, clinical response (at least a 50% reduction in 24‐hour mean pain), physical function using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life using the EQ-5D, the proportion of participants withdrawing because of adverse events, the proportion who experienced any adverse events, and the proportion who experienced serious adverse events.

The researchers considered a change on the pain scale of 0.5-1 points to be “slight to small,” a difference above 1 up to 2 to be “moderate,” and a difference greater than 2 points to be “large.” In assessing quality of life function on a scale of 0-100, a slight to small difference was 5-10, a moderate difference was 11-20, and a large difference was above 20.

Of the 18 articles the researchers identified for qualitative synthesis, 9 met the criteria for qualitative synthesis in the meta-analysis, including 7 studies only on the knee and 2 that included the knees and hips. All nine studies compared antidepressants with placebo, with or without NSAIDs. Most focused on serotonin and norepinephrine reuptake inhibitors (SNRIs) – six studies on duloxetine and one on milnacipran – while one included fluvoxamine and one included nortriptyline.

The trials included a combined 2,122 participants who were predominantly female with an average age range of 54-66. Trials ranged from 8 to 16 weeks. Five of the trials carried risk of attrition and reporting bias, and only one trial had low risk of bias across all domains.

In five trials with SNRIs and one trial with tricyclics (nortriptyline) totaling 1,904 participants, 45% of those receiving antidepressants had a clinical response, compared with 29% of patients who received placebo (risk ratio, 1.55; 95% CI, 1.31-1.92). This absolute improvement in pain occurred in 16% more participants taking antidepressants, giving a number needed to treat (NNT) of 6. Average improvement in WOMAC physical function was 10.5 points with placebo and 16.2 points with antidepressants, indicating a “small, clinically unimportant response,” the researchers concluded.

Withdrawals because of adverse events included 11% of the antidepressant group and 5% of the placebo group (RR, 2.15; 95% CI, 1.56-2.87), putting the NNT for a harmful outcome at 17.

For all nine trials together, however, the mean reduction in pain from antidepressants was 2.3 points, compared with 1.7 points with placebo, a statistically significant but ”clinically unimportant improvement,” the researchers concluded. Adverse events occurred in 64% of the antidepressant group, compared with 49% of the placebo group (RR, 1.27; 95% CI, 1.15-1.41), which put the NNT for a harmful outcome at 7. No significant difference in serious adverse events occurred between the groups.

The analysis was limited by the low number of trials, most of which were sponsored by industry and most of which used duloxetine. Further, few of the studies enrolled patients with osteoarthritis of the hip, none assessed medium- or long-term effects, and none stratified the participants for different types of pain (neuropathic-like or central or peripheral pain sensitization).

“My general impression is that there was a statistically significant difference found in favor of duloxetine and the antidepressants,” David J. Hunter, MBBS, PhD, MSc, of the University of Sydney, said after the presentation. “There is a real risk of harm, which I think is important to take into consideration, but at least for me as a clinician and in advising other clinicians, it’s one tool in our armamentarium. I think it’s really important to allow patients to make an informed decision about the potential benefit, the real risk of harm, and the fact that it is quite useful in some patients, and I use it in my clinical practice.”

Jeffrey N. Katz, MD, MS, of Brigham and Women’s Hospital in Boston, said he uses antidepressants in the same way in his practice and that other types of medications, such as TNF inhibitors, also carry risk of harm that may exceed that of antidepressants.

“I’ve had lots of people start duloxetine, and if they stop it, it’s usually because they just don’t tolerate it very well,” Dr. Katz said.

“We don’t want to throw too many things away,” Dr. Hunter added. “Our patients don’t necessarily have a lot of choices here from a pharmacologic perspective, so I think it’s one of those options that I want to keep in my tool kit, and that’s not necessarily going to change.”

The research did not involve outside funding, and Dr. Wluka reported having no industry disclosures. Disclosure information was unavailable for Dr. Katz and Dr. Hunter. The Congress was sponsored by the Osteoarthritis Research Society International.

The small size of a new study of the feasibility of tapering conventional synthetic disease-modifying antirheumatic drug (csDMARD) doses to half for patients with rheumatoid arthritis in remission, and then to zero, makes suspect the validity of its finding of no statistical difference between continuing half doses and stopping altogether, according to one rheumatologist’s analysis.

In the open-label, randomized trial of 56 patients, which was published as a research letter in JAMA, more patients in the group that discontinued csDMARDs experienced flares within 1 year than did the half-dose group, but this difference was not statistically significant.

Most patients in the drug-free group did not experience disease flares, the authors note.

“The results show that in this population, a majority of patients remained flare-free for at least a year after csDMARD discontinuation. This highlights a potential for drug-free remission in a subgroup of RA patients, and the data provide a basis for shared decision-making in this patient group. We know that tapering is a common question from patients and thus think that the data are especially clinically relevant,” first author Siri Lillegraven, MD, MPH, PhD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases at the Diakonhjemmet Hospital, Oslo, said in an interview.

While several studies have demonstrated that patients with RA can maintain remission on lower doses of medication, James O’Dell, MD, chief of the Division of Rheumatology at the University of Nebraska Medical Center, Omaha, urged caution in interpreting these results because the study was so small – just 56 patients. “Every analysis they did favored staying on treatment, but the confidence interval slightly crossed null, so they can’t say [that group] was superior,” Dr. O’Dell said in an interview. He was not involved in the research. “Had this study been double this size and they got the same results, they would have clearly shown that staying on medicines were superior,” he said.

Dr. Lillegraven acknowledged the impact of the trial’s small sample size. “This is a study with a limited study sample, and it is conceivable that a larger study might have shown a statistical difference between the groups,” she said.

In addition to the small number of patients in the study, Dr. O’Dell also noted that this study group was already a selected group of patients who had maintained remission on half-dose therapy for at least 1 year. Even then, “what they showed was that 39% of the patients who they discontinued [then] flared, compared with 17% when they didn’t taper [off medication],” he said. “That’s a pretty important clinical difference.”

While Dr. O’Dell thinks the study was too small to inform practice, he emphasized that tapering off full doses of medications can be beneficial for patients with RA that has been in remission for 6 months or longer. “It seems to take less medicines to keep somebody in remission than it did to get them there in the first place,” he said. “I come out strongly in favor of tapering medications in rheumatoid arthritis patients who are in remission, and that includes tapering and stopping biologics if patients are on conventional therapy,” he added, “but tapering patients off all of their conventional therapy is something that I think is a bridge too far.”

This trial was the second part of the ARCTIC REWIND study, which involved patients with RA that was in sustained remission, per their Disease Activity Score. In the first part of the trial, 160 participants from 10 hospitals in Norway were enrolled and were randomly assigned to either continue their standard csDMARD dosing or taper down to a half dose. Patients whose doses were tapered to a half dose and whose conditions were in remission for 1 year were eligible for the second half the study.

Of the 56 participants who were included, 26 discontinued csDMARD therapy, while 30 continued taking a half dose for 12 months of follow-up. Most patients in both groups had received methotrexate monotherapy (21 in the discontinuation group and 26 in the continued half-dosing group). Triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) was used by three patients in the discontinuation group and by two in the half-dose group. Two additional patients in the discontinuation group and two in the half-dose group took other mono/duo therapies. Clinic visits occurred every 4 months; visits were more frequent if there was an increase in disease activity. For patients who experienced a disease flare, full-dose csDMARD treatment was resumed.

Ten patients in the discontinuation group experienced flares during 1 year, compared with five patients in the half-dose group. The risk difference between the two groups was not statistically significant (RD, 21.5%; 95% CI, –3.4% to 49.7%). The median time to flare was 179 days in the discontinuation group and 133 days in the half-dose group.

Of those who experienced flares, 8 of 10 patients in the discontinuation group and 2 of 5 in the half-dose group regained remission when full-dose therapy was resumed.

The study was funded by the Research Council of Norway and the South-Eastern Norway Regional Health Authorities. Many of the authors disclosed financial ties to pharmaceutical companies. Dr. O’Dell disclosed no relevant financial relationships.

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

The small size of a new study of the feasibility of tapering conventional synthetic disease-modifying antirheumatic drug (csDMARD) doses to half for patients with rheumatoid arthritis in remission, and then to zero, makes suspect the validity of its finding of no statistical difference between continuing half doses and stopping altogether, according to one rheumatologist’s analysis.

In the open-label, randomized trial of 56 patients, which was published as a research letter in JAMA, more patients in the group that discontinued csDMARDs experienced flares within 1 year than did the half-dose group, but this difference was not statistically significant.

Most patients in the drug-free group did not experience disease flares, the authors note.

“The results show that in this population, a majority of patients remained flare-free for at least a year after csDMARD discontinuation. This highlights a potential for drug-free remission in a subgroup of RA patients, and the data provide a basis for shared decision-making in this patient group. We know that tapering is a common question from patients and thus think that the data are especially clinically relevant,” first author Siri Lillegraven, MD, MPH, PhD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases at the Diakonhjemmet Hospital, Oslo, said in an interview.

While several studies have demonstrated that patients with RA can maintain remission on lower doses of medication, James O’Dell, MD, chief of the Division of Rheumatology at the University of Nebraska Medical Center, Omaha, urged caution in interpreting these results because the study was so small – just 56 patients. “Every analysis they did favored staying on treatment, but the confidence interval slightly crossed null, so they can’t say [that group] was superior,” Dr. O’Dell said in an interview. He was not involved in the research. “Had this study been double this size and they got the same results, they would have clearly shown that staying on medicines were superior,” he said.

Dr. Lillegraven acknowledged the impact of the trial’s small sample size. “This is a study with a limited study sample, and it is conceivable that a larger study might have shown a statistical difference between the groups,” she said.

In addition to the small number of patients in the study, Dr. O’Dell also noted that this study group was already a selected group of patients who had maintained remission on half-dose therapy for at least 1 year. Even then, “what they showed was that 39% of the patients who they discontinued [then] flared, compared with 17% when they didn’t taper [off medication],” he said. “That’s a pretty important clinical difference.”

While Dr. O’Dell thinks the study was too small to inform practice, he emphasized that tapering off full doses of medications can be beneficial for patients with RA that has been in remission for 6 months or longer. “It seems to take less medicines to keep somebody in remission than it did to get them there in the first place,” he said. “I come out strongly in favor of tapering medications in rheumatoid arthritis patients who are in remission, and that includes tapering and stopping biologics if patients are on conventional therapy,” he added, “but tapering patients off all of their conventional therapy is something that I think is a bridge too far.”

This trial was the second part of the ARCTIC REWIND study, which involved patients with RA that was in sustained remission, per their Disease Activity Score. In the first part of the trial, 160 participants from 10 hospitals in Norway were enrolled and were randomly assigned to either continue their standard csDMARD dosing or taper down to a half dose. Patients whose doses were tapered to a half dose and whose conditions were in remission for 1 year were eligible for the second half the study.

Of the 56 participants who were included, 26 discontinued csDMARD therapy, while 30 continued taking a half dose for 12 months of follow-up. Most patients in both groups had received methotrexate monotherapy (21 in the discontinuation group and 26 in the continued half-dosing group). Triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) was used by three patients in the discontinuation group and by two in the half-dose group. Two additional patients in the discontinuation group and two in the half-dose group took other mono/duo therapies. Clinic visits occurred every 4 months; visits were more frequent if there was an increase in disease activity. For patients who experienced a disease flare, full-dose csDMARD treatment was resumed.

Ten patients in the discontinuation group experienced flares during 1 year, compared with five patients in the half-dose group. The risk difference between the two groups was not statistically significant (RD, 21.5%; 95% CI, –3.4% to 49.7%). The median time to flare was 179 days in the discontinuation group and 133 days in the half-dose group.

Of those who experienced flares, 8 of 10 patients in the discontinuation group and 2 of 5 in the half-dose group regained remission when full-dose therapy was resumed.

The study was funded by the Research Council of Norway and the South-Eastern Norway Regional Health Authorities. Many of the authors disclosed financial ties to pharmaceutical companies. Dr. O’Dell disclosed no relevant financial relationships.

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

The small size of a new study of the feasibility of tapering conventional synthetic disease-modifying antirheumatic drug (csDMARD) doses to half for patients with rheumatoid arthritis in remission, and then to zero, makes suspect the validity of its finding of no statistical difference between continuing half doses and stopping altogether, according to one rheumatologist’s analysis.

In the open-label, randomized trial of 56 patients, which was published as a research letter in JAMA, more patients in the group that discontinued csDMARDs experienced flares within 1 year than did the half-dose group, but this difference was not statistically significant.

Most patients in the drug-free group did not experience disease flares, the authors note.

“The results show that in this population, a majority of patients remained flare-free for at least a year after csDMARD discontinuation. This highlights a potential for drug-free remission in a subgroup of RA patients, and the data provide a basis for shared decision-making in this patient group. We know that tapering is a common question from patients and thus think that the data are especially clinically relevant,” first author Siri Lillegraven, MD, MPH, PhD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases at the Diakonhjemmet Hospital, Oslo, said in an interview.

While several studies have demonstrated that patients with RA can maintain remission on lower doses of medication, James O’Dell, MD, chief of the Division of Rheumatology at the University of Nebraska Medical Center, Omaha, urged caution in interpreting these results because the study was so small – just 56 patients. “Every analysis they did favored staying on treatment, but the confidence interval slightly crossed null, so they can’t say [that group] was superior,” Dr. O’Dell said in an interview. He was not involved in the research. “Had this study been double this size and they got the same results, they would have clearly shown that staying on medicines were superior,” he said.

Dr. Lillegraven acknowledged the impact of the trial’s small sample size. “This is a study with a limited study sample, and it is conceivable that a larger study might have shown a statistical difference between the groups,” she said.

In addition to the small number of patients in the study, Dr. O’Dell also noted that this study group was already a selected group of patients who had maintained remission on half-dose therapy for at least 1 year. Even then, “what they showed was that 39% of the patients who they discontinued [then] flared, compared with 17% when they didn’t taper [off medication],” he said. “That’s a pretty important clinical difference.”

While Dr. O’Dell thinks the study was too small to inform practice, he emphasized that tapering off full doses of medications can be beneficial for patients with RA that has been in remission for 6 months or longer. “It seems to take less medicines to keep somebody in remission than it did to get them there in the first place,” he said. “I come out strongly in favor of tapering medications in rheumatoid arthritis patients who are in remission, and that includes tapering and stopping biologics if patients are on conventional therapy,” he added, “but tapering patients off all of their conventional therapy is something that I think is a bridge too far.”

This trial was the second part of the ARCTIC REWIND study, which involved patients with RA that was in sustained remission, per their Disease Activity Score. In the first part of the trial, 160 participants from 10 hospitals in Norway were enrolled and were randomly assigned to either continue their standard csDMARD dosing or taper down to a half dose. Patients whose doses were tapered to a half dose and whose conditions were in remission for 1 year were eligible for the second half the study.

Of the 56 participants who were included, 26 discontinued csDMARD therapy, while 30 continued taking a half dose for 12 months of follow-up. Most patients in both groups had received methotrexate monotherapy (21 in the discontinuation group and 26 in the continued half-dosing group). Triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) was used by three patients in the discontinuation group and by two in the half-dose group. Two additional patients in the discontinuation group and two in the half-dose group took other mono/duo therapies. Clinic visits occurred every 4 months; visits were more frequent if there was an increase in disease activity. For patients who experienced a disease flare, full-dose csDMARD treatment was resumed.

Ten patients in the discontinuation group experienced flares during 1 year, compared with five patients in the half-dose group. The risk difference between the two groups was not statistically significant (RD, 21.5%; 95% CI, –3.4% to 49.7%). The median time to flare was 179 days in the discontinuation group and 133 days in the half-dose group.

Of those who experienced flares, 8 of 10 patients in the discontinuation group and 2 of 5 in the half-dose group regained remission when full-dose therapy was resumed.

The study was funded by the Research Council of Norway and the South-Eastern Norway Regional Health Authorities. Many of the authors disclosed financial ties to pharmaceutical companies. Dr. O’Dell disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved a citrate-free, 100 mg/mL formulation of the biosimilar adalimumab-adaz (Hyrimoz), according to a statement from manufacturer Sandoz.

Hyrimoz, a tumor necrosis factor (TNF) blocker that is biosimilar to its reference product Humira, was approved by the FDA in 2018 at a concentration of 50 mg/mL for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The high-concentration formula is indicated for these same conditions.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Sandoz said that it intends to launch the citrate-free formulation in the United States on July 1. It will be one of up to nine other adalimumab biosimilars that are expected to launch in July. On January 31, Amjevita (adalimumab-atto) became the first adalimumab biosimilar to launch in the United States.

The current label for Hyrimoz contains a black box warning emphasizing certain risks, notably the increased risk for serious infections, such as tuberculosis or sepsis, and an increased risk of malignancy, particularly lymphomas.

Adverse effects associated with Hyrimoz with an incidence greater than 10% include upper respiratory infections and sinusitis, injection-site reactions, headache, and rash.

The approval for the high-concentration formulation was based on data from a phase 1 pharmacokinetics bridging study that compared Hyrimoz 50 mg/mL and citrate-free Hyrimoz 100 mg/mL.

“This study met all of the primary objectives, demonstrating comparable pharmacokinetics and showing similar safety and immunogenicity of the Hyrimoz 50 mg/mL and Hyrimoz [100 mg/mL],” according to Sandoz, a division of Novartis.

The approval for Hyrimoz 50 mg/mL in 2018 was based on preclinical and clinical research comparing Hyrimoz and Humira. In a phase 3 trial published in the British Journal of Dermatology, which included adults with clinically stable but active moderate to severe chronic plaque psoriasis, Hyrimoz and Humira showed a similar percentage of patients met the primary endpoint of a 75% reduction or more in Psoriasis Area and Severity Index (PASI 75) score at 16 weeks, compared with baseline (66.8% and 65%, respectively).

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

The Food and Drug Administration has approved a citrate-free, 100 mg/mL formulation of the biosimilar adalimumab-adaz (Hyrimoz), according to a statement from manufacturer Sandoz.

Hyrimoz, a tumor necrosis factor (TNF) blocker that is biosimilar to its reference product Humira, was approved by the FDA in 2018 at a concentration of 50 mg/mL for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The high-concentration formula is indicated for these same conditions.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Sandoz said that it intends to launch the citrate-free formulation in the United States on July 1. It will be one of up to nine other adalimumab biosimilars that are expected to launch in July. On January 31, Amjevita (adalimumab-atto) became the first adalimumab biosimilar to launch in the United States.

The current label for Hyrimoz contains a black box warning emphasizing certain risks, notably the increased risk for serious infections, such as tuberculosis or sepsis, and an increased risk of malignancy, particularly lymphomas.

Adverse effects associated with Hyrimoz with an incidence greater than 10% include upper respiratory infections and sinusitis, injection-site reactions, headache, and rash.

The approval for the high-concentration formulation was based on data from a phase 1 pharmacokinetics bridging study that compared Hyrimoz 50 mg/mL and citrate-free Hyrimoz 100 mg/mL.

“This study met all of the primary objectives, demonstrating comparable pharmacokinetics and showing similar safety and immunogenicity of the Hyrimoz 50 mg/mL and Hyrimoz [100 mg/mL],” according to Sandoz, a division of Novartis.

The approval for Hyrimoz 50 mg/mL in 2018 was based on preclinical and clinical research comparing Hyrimoz and Humira. In a phase 3 trial published in the British Journal of Dermatology, which included adults with clinically stable but active moderate to severe chronic plaque psoriasis, Hyrimoz and Humira showed a similar percentage of patients met the primary endpoint of a 75% reduction or more in Psoriasis Area and Severity Index (PASI 75) score at 16 weeks, compared with baseline (66.8% and 65%, respectively).

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

The Food and Drug Administration has approved a citrate-free, 100 mg/mL formulation of the biosimilar adalimumab-adaz (Hyrimoz), according to a statement from manufacturer Sandoz.

Hyrimoz, a tumor necrosis factor (TNF) blocker that is biosimilar to its reference product Humira, was approved by the FDA in 2018 at a concentration of 50 mg/mL for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The high-concentration formula is indicated for these same conditions.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Sandoz said that it intends to launch the citrate-free formulation in the United States on July 1. It will be one of up to nine other adalimumab biosimilars that are expected to launch in July. On January 31, Amjevita (adalimumab-atto) became the first adalimumab biosimilar to launch in the United States.

The current label for Hyrimoz contains a black box warning emphasizing certain risks, notably the increased risk for serious infections, such as tuberculosis or sepsis, and an increased risk of malignancy, particularly lymphomas.

Adverse effects associated with Hyrimoz with an incidence greater than 10% include upper respiratory infections and sinusitis, injection-site reactions, headache, and rash.

The approval for the high-concentration formulation was based on data from a phase 1 pharmacokinetics bridging study that compared Hyrimoz 50 mg/mL and citrate-free Hyrimoz 100 mg/mL.

“This study met all of the primary objectives, demonstrating comparable pharmacokinetics and showing similar safety and immunogenicity of the Hyrimoz 50 mg/mL and Hyrimoz [100 mg/mL],” according to Sandoz, a division of Novartis.

The approval for Hyrimoz 50 mg/mL in 2018 was based on preclinical and clinical research comparing Hyrimoz and Humira. In a phase 3 trial published in the British Journal of Dermatology, which included adults with clinically stable but active moderate to severe chronic plaque psoriasis, Hyrimoz and Humira showed a similar percentage of patients met the primary endpoint of a 75% reduction or more in Psoriasis Area and Severity Index (PASI 75) score at 16 weeks, compared with baseline (66.8% and 65%, respectively).

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

Anifrolumab appears to improve outcomes in patients with refractory discoid lupus erythematosus (DLE), especially in those with severe or recalcitrant disease, a small retrospective study reports.

DLE, the most common form of chronic cutaneous lupus erythematosus, can permanently scar and disfigure patients, and traditional treatments such as antimalarials, steroid-sparing immunosuppressive agents, thalidomide, retinoids, and lenalidomide don’t consistently improve refractory DLE, the authors noted.

“All patients demonstrated significant improvement in symptomatology and disease activity within 2 months of initiating anifrolumab,” lead study author Katharina Shaw, MD, of the department of dermatology of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues wrote in a research letter published in JAMA Dermatology. “These early results highlight the potential for anifrolumab to be a viable therapeutic option for patients with DLE, particularly those with severe or recalcitrant disease.”

The Food and Drug Administration approved anifrolumab (Saphnelo), a human monoclonal antibody targeting type 1 interferon receptor subunit 1, in 2021 for adults with moderate to severe systemic lupus erythematosus, but it has not been approved for the treatment of DLE.

Dr. Shaw and colleagues queried the medical records from Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, to find all cases of DLE based on biopsy, expert opinion, or both from January 2000 to October 2022.

The researchers identified eight female patients who had received anifrolumab for at least 8 weeks. The women were aged between 19 and 75 years (median, 42.5 years), and all had DLE recalcitrant to standard therapies and had been treated with hydroxychloroquine and between 1 and 10 other drugs, most commonly methotrexate and mycophenolate mofetil (MMF).

The authors looked for improvements in patient-reported symptoms and Cutaneous Lupus Erythematosus Disease Area and Severity Index scores, including CLASI A (activity) score 0-70, and CLASI-D (damage) score 0-56.

All patients showed significantly improved symptoms and disease activity within 2 months of their first infusion of the treatment. The mean decrease and mean percentage decrease in CLASI-A scores were 17.1 and 65.1%, respectively. The mean decrease and mean percentage decrease in CLASI-D scores were 0.5 and 2.9%, respectively.

The rapid clinical improvements with anifrolumab, compared with improvements with traditional medications, were striking, the authors wrote. “Given the risk for permanent scarring, dyspigmentation, and alopecia with poorly controlled DLE, the importance of rapidly mitigating disease activity cannot be overemphasized.”

They acknowledged that the results are limited by the study’s small sample size and retrospective design, and they recommend larger related prospective studies.

Dr. Kaveh Ardalan

Asked to comment on the results, Kaveh Ardalan, MD, MS, assistant professor of pediatrics in the division of pediatric rheumatology at Duke University, Durham, N.C., said that finding new DLE therapeutics is important because of the huge impact of uncontrolled DLE on patients’ quality of life, body image, and social roles.

Dr. Ardalan noted that he sees DLE in his pediatric patients, “either as an isolated finding or in the context of systemic lupus erythematosus. Anifrolumab is not approved by the FDA to treat DLE or children.

“Randomized controlled trials, including the TULIP-1 and TULIP-2 studies of anifrolumab in systemic lupus, have indicated that lupus skin manifestations can improve in patients who receive anifrolumab,” said Dr. Ardalan, who was not involved in the study. “And we know that type I interferons are major drivers of cutaneous disease activity in patients with lupus, so targeting that mechanism with anifrolumab makes biological sense.”

The authors’ use of the validated CLASI classification system to quantify disease activity and damage over time, and their determination of the length of time for the drug to take effect are strengths of the study, he added.

Funding information was not provided. Two authors reported financial relationships with Pfizer, which does not manufacture anifrolumab. Dr. Ardalan reported no conflicts of interest with the study.

Anifrolumab appears to improve outcomes in patients with refractory discoid lupus erythematosus (DLE), especially in those with severe or recalcitrant disease, a small retrospective study reports.

DLE, the most common form of chronic cutaneous lupus erythematosus, can permanently scar and disfigure patients, and traditional treatments such as antimalarials, steroid-sparing immunosuppressive agents, thalidomide, retinoids, and lenalidomide don’t consistently improve refractory DLE, the authors noted.

“All patients demonstrated significant improvement in symptomatology and disease activity within 2 months of initiating anifrolumab,” lead study author Katharina Shaw, MD, of the department of dermatology of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues wrote in a research letter published in JAMA Dermatology. “These early results highlight the potential for anifrolumab to be a viable therapeutic option for patients with DLE, particularly those with severe or recalcitrant disease.”

The Food and Drug Administration approved anifrolumab (Saphnelo), a human monoclonal antibody targeting type 1 interferon receptor subunit 1, in 2021 for adults with moderate to severe systemic lupus erythematosus, but it has not been approved for the treatment of DLE.

Dr. Shaw and colleagues queried the medical records from Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, to find all cases of DLE based on biopsy, expert opinion, or both from January 2000 to October 2022.

The researchers identified eight female patients who had received anifrolumab for at least 8 weeks. The women were aged between 19 and 75 years (median, 42.5 years), and all had DLE recalcitrant to standard therapies and had been treated with hydroxychloroquine and between 1 and 10 other drugs, most commonly methotrexate and mycophenolate mofetil (MMF).

The authors looked for improvements in patient-reported symptoms and Cutaneous Lupus Erythematosus Disease Area and Severity Index scores, including CLASI A (activity) score 0-70, and CLASI-D (damage) score 0-56.

All patients showed significantly improved symptoms and disease activity within 2 months of their first infusion of the treatment. The mean decrease and mean percentage decrease in CLASI-A scores were 17.1 and 65.1%, respectively. The mean decrease and mean percentage decrease in CLASI-D scores were 0.5 and 2.9%, respectively.

The rapid clinical improvements with anifrolumab, compared with improvements with traditional medications, were striking, the authors wrote. “Given the risk for permanent scarring, dyspigmentation, and alopecia with poorly controlled DLE, the importance of rapidly mitigating disease activity cannot be overemphasized.”

They acknowledged that the results are limited by the study’s small sample size and retrospective design, and they recommend larger related prospective studies.

Dr. Kaveh Ardalan

Asked to comment on the results, Kaveh Ardalan, MD, MS, assistant professor of pediatrics in the division of pediatric rheumatology at Duke University, Durham, N.C., said that finding new DLE therapeutics is important because of the huge impact of uncontrolled DLE on patients’ quality of life, body image, and social roles.

Dr. Ardalan noted that he sees DLE in his pediatric patients, “either as an isolated finding or in the context of systemic lupus erythematosus. Anifrolumab is not approved by the FDA to treat DLE or children.

“Randomized controlled trials, including the TULIP-1 and TULIP-2 studies of anifrolumab in systemic lupus, have indicated that lupus skin manifestations can improve in patients who receive anifrolumab,” said Dr. Ardalan, who was not involved in the study. “And we know that type I interferons are major drivers of cutaneous disease activity in patients with lupus, so targeting that mechanism with anifrolumab makes biological sense.”

The authors’ use of the validated CLASI classification system to quantify disease activity and damage over time, and their determination of the length of time for the drug to take effect are strengths of the study, he added.

Funding information was not provided. Two authors reported financial relationships with Pfizer, which does not manufacture anifrolumab. Dr. Ardalan reported no conflicts of interest with the study.

Anifrolumab appears to improve outcomes in patients with refractory discoid lupus erythematosus (DLE), especially in those with severe or recalcitrant disease, a small retrospective study reports.

DLE, the most common form of chronic cutaneous lupus erythematosus, can permanently scar and disfigure patients, and traditional treatments such as antimalarials, steroid-sparing immunosuppressive agents, thalidomide, retinoids, and lenalidomide don’t consistently improve refractory DLE, the authors noted.

“All patients demonstrated significant improvement in symptomatology and disease activity within 2 months of initiating anifrolumab,” lead study author Katharina Shaw, MD, of the department of dermatology of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues wrote in a research letter published in JAMA Dermatology. “These early results highlight the potential for anifrolumab to be a viable therapeutic option for patients with DLE, particularly those with severe or recalcitrant disease.”

The Food and Drug Administration approved anifrolumab (Saphnelo), a human monoclonal antibody targeting type 1 interferon receptor subunit 1, in 2021 for adults with moderate to severe systemic lupus erythematosus, but it has not been approved for the treatment of DLE.

Dr. Shaw and colleagues queried the medical records from Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, to find all cases of DLE based on biopsy, expert opinion, or both from January 2000 to October 2022.

The researchers identified eight female patients who had received anifrolumab for at least 8 weeks. The women were aged between 19 and 75 years (median, 42.5 years), and all had DLE recalcitrant to standard therapies and had been treated with hydroxychloroquine and between 1 and 10 other drugs, most commonly methotrexate and mycophenolate mofetil (MMF).

The authors looked for improvements in patient-reported symptoms and Cutaneous Lupus Erythematosus Disease Area and Severity Index scores, including CLASI A (activity) score 0-70, and CLASI-D (damage) score 0-56.

All patients showed significantly improved symptoms and disease activity within 2 months of their first infusion of the treatment. The mean decrease and mean percentage decrease in CLASI-A scores were 17.1 and 65.1%, respectively. The mean decrease and mean percentage decrease in CLASI-D scores were 0.5 and 2.9%, respectively.

The rapid clinical improvements with anifrolumab, compared with improvements with traditional medications, were striking, the authors wrote. “Given the risk for permanent scarring, dyspigmentation, and alopecia with poorly controlled DLE, the importance of rapidly mitigating disease activity cannot be overemphasized.”

They acknowledged that the results are limited by the study’s small sample size and retrospective design, and they recommend larger related prospective studies.

Dr. Kaveh Ardalan

Asked to comment on the results, Kaveh Ardalan, MD, MS, assistant professor of pediatrics in the division of pediatric rheumatology at Duke University, Durham, N.C., said that finding new DLE therapeutics is important because of the huge impact of uncontrolled DLE on patients’ quality of life, body image, and social roles.

Dr. Ardalan noted that he sees DLE in his pediatric patients, “either as an isolated finding or in the context of systemic lupus erythematosus. Anifrolumab is not approved by the FDA to treat DLE or children.

“Randomized controlled trials, including the TULIP-1 and TULIP-2 studies of anifrolumab in systemic lupus, have indicated that lupus skin manifestations can improve in patients who receive anifrolumab,” said Dr. Ardalan, who was not involved in the study. “And we know that type I interferons are major drivers of cutaneous disease activity in patients with lupus, so targeting that mechanism with anifrolumab makes biological sense.”

The authors’ use of the validated CLASI classification system to quantify disease activity and damage over time, and their determination of the length of time for the drug to take effect are strengths of the study, he added.

Funding information was not provided. Two authors reported financial relationships with Pfizer, which does not manufacture anifrolumab. Dr. Ardalan reported no conflicts of interest with the study.