Rheumatology

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

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

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

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

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

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

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

Women with psoriatic arthritis (PsA) presented with more severe disease at baseline and were less likely to achieve favorable outcomes after 12 months of treatment with either ustekinumab (Stelara) or a tumor necrosis factor (TNF) inhibitor, compared with men, according to a post hoc analysis of data from nearly 1,000 individuals.

Although data suggest that the overall prevalence of PsA is similar across genders, recent studies have identified differences in various aspects of PsA between men and women, wrote Arno W.R. Van Kuijk, MD, of Amsterdam Rheumatology and Immunology Center, and colleagues wrote in a study published in Rheumatology.

“Accumulating evidence in multiple rheumatic diseases indicates that gender may influence the likelihood of achieving the desired outcome with treatment,” but studies of differences in treatment response according to gender are limited, they said.

The researchers conducted a post hoc analysis of women and men with PsA who were part of PsABio, a noninterventional European study of patients with PsA. All participants were starting first-, second-, or third-line treatment with ustekinumab or a TNF inhibitor. The primary outcome was response to treatment at 12 months. Disease activity was assessed using the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), the Health Assessment Questionnaire–Disability Index (HAQ-DI), and total score on the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire.

Baseline available data for 512 women and 417 men showed the mean duration of disease was similar between genders (6.7 years for females and 6.9 years for males); body mass index was similar, as was the proportion of male and female patients receiving concomitant conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Females scored significantly worse than males on disease activity assessments at baseline with mean cDAPSA scores of 32.3 and 26.8, respectively.

The final analysis of 895 patients with baseline data and a postbaseline assessment included 439 who started ustekinumab (247 females, 192 males), and 456 who started a TNF inhibitor (248 females, 208 males).

At 12 months, females showed smaller degrees of improvement than males; 57.8% and 80.3%, respectively, achieved low disease activity based on cDAPSA scores, while 33.7% and 55.5% of females and males, respectively, achieved minimal disease activity. Measures of disability were higher in females than males, with HAQ-DI scores of 0.85 versus 0.50. PsAID-12 scores also were higher for females, compared with males (3.5 vs. 2.4).

A total of 81.7% of patients were on their initial biologic DMARD after 12 months, but more females than males who were taking ustekinumab or a TNF inhibitor changed or discontinued treatment.

Treatment persistence was significantly lower in females than males (P = .01), and lack of effectiveness was the main reason for discontinuation regardless of gender.

“The analysis of gender subgroup results of the PsABio study has expanded previously published observations that men and women with PsA have different experiences with the disease activity, clinical manifestations, impact on health-related quality of life, response to [biologic] DMARDs, and drug persistence,” the researchers wrote.

The lack of a medication protocol in the PsABio study limited the conclusions that could be drawn from the post hoc analysis, but the results were strengthened by the relatively large and diverse sample size and the inclusion of responses to more than one medication, the researchers noted.

The study was supported by Janssen. Dr. Van Kuijk disclosed serving as a consultant and receiving grant support from Janssen and other companies; several coauthors also disclosed relationships with Janssen.

Women with psoriatic arthritis (PsA) presented with more severe disease at baseline and were less likely to achieve favorable outcomes after 12 months of treatment with either ustekinumab (Stelara) or a tumor necrosis factor (TNF) inhibitor, compared with men, according to a post hoc analysis of data from nearly 1,000 individuals.

Although data suggest that the overall prevalence of PsA is similar across genders, recent studies have identified differences in various aspects of PsA between men and women, wrote Arno W.R. Van Kuijk, MD, of Amsterdam Rheumatology and Immunology Center, and colleagues wrote in a study published in Rheumatology.

“Accumulating evidence in multiple rheumatic diseases indicates that gender may influence the likelihood of achieving the desired outcome with treatment,” but studies of differences in treatment response according to gender are limited, they said.

The researchers conducted a post hoc analysis of women and men with PsA who were part of PsABio, a noninterventional European study of patients with PsA. All participants were starting first-, second-, or third-line treatment with ustekinumab or a TNF inhibitor. The primary outcome was response to treatment at 12 months. Disease activity was assessed using the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), the Health Assessment Questionnaire–Disability Index (HAQ-DI), and total score on the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire.

Baseline available data for 512 women and 417 men showed the mean duration of disease was similar between genders (6.7 years for females and 6.9 years for males); body mass index was similar, as was the proportion of male and female patients receiving concomitant conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Females scored significantly worse than males on disease activity assessments at baseline with mean cDAPSA scores of 32.3 and 26.8, respectively.

The final analysis of 895 patients with baseline data and a postbaseline assessment included 439 who started ustekinumab (247 females, 192 males), and 456 who started a TNF inhibitor (248 females, 208 males).

At 12 months, females showed smaller degrees of improvement than males; 57.8% and 80.3%, respectively, achieved low disease activity based on cDAPSA scores, while 33.7% and 55.5% of females and males, respectively, achieved minimal disease activity. Measures of disability were higher in females than males, with HAQ-DI scores of 0.85 versus 0.50. PsAID-12 scores also were higher for females, compared with males (3.5 vs. 2.4).

A total of 81.7% of patients were on their initial biologic DMARD after 12 months, but more females than males who were taking ustekinumab or a TNF inhibitor changed or discontinued treatment.

Treatment persistence was significantly lower in females than males (P = .01), and lack of effectiveness was the main reason for discontinuation regardless of gender.

“The analysis of gender subgroup results of the PsABio study has expanded previously published observations that men and women with PsA have different experiences with the disease activity, clinical manifestations, impact on health-related quality of life, response to [biologic] DMARDs, and drug persistence,” the researchers wrote.

The lack of a medication protocol in the PsABio study limited the conclusions that could be drawn from the post hoc analysis, but the results were strengthened by the relatively large and diverse sample size and the inclusion of responses to more than one medication, the researchers noted.

The study was supported by Janssen. Dr. Van Kuijk disclosed serving as a consultant and receiving grant support from Janssen and other companies; several coauthors also disclosed relationships with Janssen.

Women with psoriatic arthritis (PsA) presented with more severe disease at baseline and were less likely to achieve favorable outcomes after 12 months of treatment with either ustekinumab (Stelara) or a tumor necrosis factor (TNF) inhibitor, compared with men, according to a post hoc analysis of data from nearly 1,000 individuals.

Although data suggest that the overall prevalence of PsA is similar across genders, recent studies have identified differences in various aspects of PsA between men and women, wrote Arno W.R. Van Kuijk, MD, of Amsterdam Rheumatology and Immunology Center, and colleagues wrote in a study published in Rheumatology.

“Accumulating evidence in multiple rheumatic diseases indicates that gender may influence the likelihood of achieving the desired outcome with treatment,” but studies of differences in treatment response according to gender are limited, they said.

The researchers conducted a post hoc analysis of women and men with PsA who were part of PsABio, a noninterventional European study of patients with PsA. All participants were starting first-, second-, or third-line treatment with ustekinumab or a TNF inhibitor. The primary outcome was response to treatment at 12 months. Disease activity was assessed using the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), the Health Assessment Questionnaire–Disability Index (HAQ-DI), and total score on the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire.

Baseline available data for 512 women and 417 men showed the mean duration of disease was similar between genders (6.7 years for females and 6.9 years for males); body mass index was similar, as was the proportion of male and female patients receiving concomitant conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Females scored significantly worse than males on disease activity assessments at baseline with mean cDAPSA scores of 32.3 and 26.8, respectively.

The final analysis of 895 patients with baseline data and a postbaseline assessment included 439 who started ustekinumab (247 females, 192 males), and 456 who started a TNF inhibitor (248 females, 208 males).

At 12 months, females showed smaller degrees of improvement than males; 57.8% and 80.3%, respectively, achieved low disease activity based on cDAPSA scores, while 33.7% and 55.5% of females and males, respectively, achieved minimal disease activity. Measures of disability were higher in females than males, with HAQ-DI scores of 0.85 versus 0.50. PsAID-12 scores also were higher for females, compared with males (3.5 vs. 2.4).

A total of 81.7% of patients were on their initial biologic DMARD after 12 months, but more females than males who were taking ustekinumab or a TNF inhibitor changed or discontinued treatment.

Treatment persistence was significantly lower in females than males (P = .01), and lack of effectiveness was the main reason for discontinuation regardless of gender.

“The analysis of gender subgroup results of the PsABio study has expanded previously published observations that men and women with PsA have different experiences with the disease activity, clinical manifestations, impact on health-related quality of life, response to [biologic] DMARDs, and drug persistence,” the researchers wrote.

The lack of a medication protocol in the PsABio study limited the conclusions that could be drawn from the post hoc analysis, but the results were strengthened by the relatively large and diverse sample size and the inclusion of responses to more than one medication, the researchers noted.

The study was supported by Janssen. Dr. Van Kuijk disclosed serving as a consultant and receiving grant support from Janssen and other companies; several coauthors also disclosed relationships with Janssen.

DENVER – People with lower expectations of how they would be able to use their knees during work activities after a total knee arthroplasty were more dissatisfied with their knee abilities 6 months after their surgery, according to a study presented at the OARSI 2023 World Congress.

Two out of 10 patients are dissatisfied after total knee arthroplasty, which is increasingly performed in younger and working patients who may have higher demands, presenter Yvonne van Zaanen, a physiotherapist in occupational health and ergonomics and a PhD candidate at Amsterdam University Medical Center, told attendees.

The findings suggest a correlation between patients’ low presurgical expectations of their ability to use their knees and having more difficulty with their knees postoperatively, she said. “We should take better care of working patients with low expectations by managing their preoperative expectations and improving their ability to perform work-related knee-straining activities in rehabilitation,” Ms. van Zaanen told attendees.

The researchers conducted a multicenter, prospective cohort study involving seven hospitals. They surveyed 175 employed individuals aged 18-65 years who were scheduled for a total knee arthroplasty and intended to return to work after their surgery. The first survey occurred before the operation, and the follow-up occurred 6 months after the surgery.

Just over half the participants were women (53%), and the average participant age was 59. Respondents had a mean body mass index (BMI) of 29 kg/m², and had a Knee injury and Osteoarthritis Outcome Score (KOOS) pain score of 42 (on a 0-to-100 scale in which lower scores are worse). About half the respondents (51%) had a job that involved knee-straining activities.

The researchers assessed participants’ ability to perform work-related, knee-straining activities using the Work, Osteoarthritis, or joint-Replacement Questionnaire (WORQ) tool, which considers the following activities: kneeling, crouching, clambering, taking the stairs, walking on rough terrain, working with hands below knee height, standing, lifting or carrying, pushing or pulling, walking on ground level, operating a vehicle, operating foot pedals, and sitting. The 0-to-100 scale rates the difficulty of using knees for each particular activity, with higher scores indicating greater ease and less pain in doing that activity.

Among the 107 patients who expected to be satisfied after their surgery, half (n = 53) were satisfied, compared with 12% (n = 13) who were unsatisfied; the remaining participants (n = 41, 38%) were neither satisfied nor dissatisfied. Among the 24 patients who expected to be dissatisfied after their surgery, one-third (n = 8) were satisfied and 42% (n = 10) were dissatisfied. The remaining 44 patients didn’t expect to be satisfied or dissatisfied before their surgery, and 41% of them were satisfied while 23% were dissatisfied.

The researchers found that patients’ expectation of their satisfaction level going into the surgery was the only preoperative factor to be prognostic for dissatisfaction 6 months after surgery, based on their WORQ score. That is, patients who expected to be dissatisfied before their surgery had approximately five times greater odds of being dissatisfied after their surgery than did those who expected to be satisfied with their ability to do knee-straining activities at work (odds ratio, 5.1; 95% confidence interval, 1.7-15.5). Among those with a WORQ score of 40, indicating a greater expectation of difficulty using their knees postoperatively, 55% were dissatisfied after their surgery, compared with 19% of those with a WORQ score of 85, who expected greater knee ability after their surgery.

The other factors that the researchers examined, which had no effect on WORQ scores, included age, sex, BMI, education, comorbidities, KOOS pain subscale, having a knee-straining job, having needed surgery because of work, or having preoperative sick leave.

One discussion prompted by the presentation focused specifically on individuals’ ability to kneel without much difficulty after their surgery, an activity that’s not typically considered likely, Ms. van Zaanen noted. One audience member, Gillian Hawker, MD, MSc, a professor of medicine in the division of rheumatology at the University of Toronto, questioned whether the field should accept that current reality from surgical intervention. Dr. Hawker described a cohort she had analyzed in which two-thirds of the participants had expected they would be able to kneel after their surgery, regardless of whether it was related to work or other activities.

“Kneeling is important, not just for work; it’s important for culture and religion and lots of other things,” Dr. Hawker said. “How will you help these people to kneel after knee replacement when the surgery isn’t really performed to enable people to do that?” In response, Ms. van Zaanen noted it might not be achievable, as the research literature demonstrates, but Dr. Hawker suggested that is itself problematic.

“I guess what I’m asking is, why are we settling for that? If it’s important to so many people, and an expectation of so many people, why don’t we technologically improve such that, post arthroplasty, people can kneel?”

Another commenter suggested that the study’s findings may not indicate a need to manage patients’ expectations prior to surgery so much as showing that some patients simply have realistic expectations of what they will and will not be able to do after knee replacement.

“Is it possible that people who had low expectations – those who expected to be dissatisfied afterwards – were appropriately understanding that they were likely to be dissatisfied afterwards, in which case, managing their expectations might do nothing for their dissatisfaction afterwards?” the commenter asked. It is likely necessary to conduct additional research about expectations before surgery and experiences after surgery to address that question, Ms. van Zaanen suggested.

Ms. van Zaanen and Dr. Hawker reported having no relevant financial relationships. The presentation did not note any external funding. The Congress was sponsored by the Osteoarthritis Research Society International.

DENVER – People with lower expectations of how they would be able to use their knees during work activities after a total knee arthroplasty were more dissatisfied with their knee abilities 6 months after their surgery, according to a study presented at the OARSI 2023 World Congress.

Two out of 10 patients are dissatisfied after total knee arthroplasty, which is increasingly performed in younger and working patients who may have higher demands, presenter Yvonne van Zaanen, a physiotherapist in occupational health and ergonomics and a PhD candidate at Amsterdam University Medical Center, told attendees.

The findings suggest a correlation between patients’ low presurgical expectations of their ability to use their knees and having more difficulty with their knees postoperatively, she said. “We should take better care of working patients with low expectations by managing their preoperative expectations and improving their ability to perform work-related knee-straining activities in rehabilitation,” Ms. van Zaanen told attendees.

The researchers conducted a multicenter, prospective cohort study involving seven hospitals. They surveyed 175 employed individuals aged 18-65 years who were scheduled for a total knee arthroplasty and intended to return to work after their surgery. The first survey occurred before the operation, and the follow-up occurred 6 months after the surgery.

Just over half the participants were women (53%), and the average participant age was 59. Respondents had a mean body mass index (BMI) of 29 kg/m², and had a Knee injury and Osteoarthritis Outcome Score (KOOS) pain score of 42 (on a 0-to-100 scale in which lower scores are worse). About half the respondents (51%) had a job that involved knee-straining activities.

The researchers assessed participants’ ability to perform work-related, knee-straining activities using the Work, Osteoarthritis, or joint-Replacement Questionnaire (WORQ) tool, which considers the following activities: kneeling, crouching, clambering, taking the stairs, walking on rough terrain, working with hands below knee height, standing, lifting or carrying, pushing or pulling, walking on ground level, operating a vehicle, operating foot pedals, and sitting. The 0-to-100 scale rates the difficulty of using knees for each particular activity, with higher scores indicating greater ease and less pain in doing that activity.

Among the 107 patients who expected to be satisfied after their surgery, half (n = 53) were satisfied, compared with 12% (n = 13) who were unsatisfied; the remaining participants (n = 41, 38%) were neither satisfied nor dissatisfied. Among the 24 patients who expected to be dissatisfied after their surgery, one-third (n = 8) were satisfied and 42% (n = 10) were dissatisfied. The remaining 44 patients didn’t expect to be satisfied or dissatisfied before their surgery, and 41% of them were satisfied while 23% were dissatisfied.

The researchers found that patients’ expectation of their satisfaction level going into the surgery was the only preoperative factor to be prognostic for dissatisfaction 6 months after surgery, based on their WORQ score. That is, patients who expected to be dissatisfied before their surgery had approximately five times greater odds of being dissatisfied after their surgery than did those who expected to be satisfied with their ability to do knee-straining activities at work (odds ratio, 5.1; 95% confidence interval, 1.7-15.5). Among those with a WORQ score of 40, indicating a greater expectation of difficulty using their knees postoperatively, 55% were dissatisfied after their surgery, compared with 19% of those with a WORQ score of 85, who expected greater knee ability after their surgery.

The other factors that the researchers examined, which had no effect on WORQ scores, included age, sex, BMI, education, comorbidities, KOOS pain subscale, having a knee-straining job, having needed surgery because of work, or having preoperative sick leave.

One discussion prompted by the presentation focused specifically on individuals’ ability to kneel without much difficulty after their surgery, an activity that’s not typically considered likely, Ms. van Zaanen noted. One audience member, Gillian Hawker, MD, MSc, a professor of medicine in the division of rheumatology at the University of Toronto, questioned whether the field should accept that current reality from surgical intervention. Dr. Hawker described a cohort she had analyzed in which two-thirds of the participants had expected they would be able to kneel after their surgery, regardless of whether it was related to work or other activities.

“Kneeling is important, not just for work; it’s important for culture and religion and lots of other things,” Dr. Hawker said. “How will you help these people to kneel after knee replacement when the surgery isn’t really performed to enable people to do that?” In response, Ms. van Zaanen noted it might not be achievable, as the research literature demonstrates, but Dr. Hawker suggested that is itself problematic.

“I guess what I’m asking is, why are we settling for that? If it’s important to so many people, and an expectation of so many people, why don’t we technologically improve such that, post arthroplasty, people can kneel?”

Another commenter suggested that the study’s findings may not indicate a need to manage patients’ expectations prior to surgery so much as showing that some patients simply have realistic expectations of what they will and will not be able to do after knee replacement.

“Is it possible that people who had low expectations – those who expected to be dissatisfied afterwards – were appropriately understanding that they were likely to be dissatisfied afterwards, in which case, managing their expectations might do nothing for their dissatisfaction afterwards?” the commenter asked. It is likely necessary to conduct additional research about expectations before surgery and experiences after surgery to address that question, Ms. van Zaanen suggested.

Ms. van Zaanen and Dr. Hawker reported having no relevant financial relationships. The presentation did not note any external funding. The Congress was sponsored by the Osteoarthritis Research Society International.

DENVER – People with lower expectations of how they would be able to use their knees during work activities after a total knee arthroplasty were more dissatisfied with their knee abilities 6 months after their surgery, according to a study presented at the OARSI 2023 World Congress.

Two out of 10 patients are dissatisfied after total knee arthroplasty, which is increasingly performed in younger and working patients who may have higher demands, presenter Yvonne van Zaanen, a physiotherapist in occupational health and ergonomics and a PhD candidate at Amsterdam University Medical Center, told attendees.

The findings suggest a correlation between patients’ low presurgical expectations of their ability to use their knees and having more difficulty with their knees postoperatively, she said. “We should take better care of working patients with low expectations by managing their preoperative expectations and improving their ability to perform work-related knee-straining activities in rehabilitation,” Ms. van Zaanen told attendees.

The researchers conducted a multicenter, prospective cohort study involving seven hospitals. They surveyed 175 employed individuals aged 18-65 years who were scheduled for a total knee arthroplasty and intended to return to work after their surgery. The first survey occurred before the operation, and the follow-up occurred 6 months after the surgery.

Just over half the participants were women (53%), and the average participant age was 59. Respondents had a mean body mass index (BMI) of 29 kg/m², and had a Knee injury and Osteoarthritis Outcome Score (KOOS) pain score of 42 (on a 0-to-100 scale in which lower scores are worse). About half the respondents (51%) had a job that involved knee-straining activities.

The researchers assessed participants’ ability to perform work-related, knee-straining activities using the Work, Osteoarthritis, or joint-Replacement Questionnaire (WORQ) tool, which considers the following activities: kneeling, crouching, clambering, taking the stairs, walking on rough terrain, working with hands below knee height, standing, lifting or carrying, pushing or pulling, walking on ground level, operating a vehicle, operating foot pedals, and sitting. The 0-to-100 scale rates the difficulty of using knees for each particular activity, with higher scores indicating greater ease and less pain in doing that activity.

Among the 107 patients who expected to be satisfied after their surgery, half (n = 53) were satisfied, compared with 12% (n = 13) who were unsatisfied; the remaining participants (n = 41, 38%) were neither satisfied nor dissatisfied. Among the 24 patients who expected to be dissatisfied after their surgery, one-third (n = 8) were satisfied and 42% (n = 10) were dissatisfied. The remaining 44 patients didn’t expect to be satisfied or dissatisfied before their surgery, and 41% of them were satisfied while 23% were dissatisfied.

The researchers found that patients’ expectation of their satisfaction level going into the surgery was the only preoperative factor to be prognostic for dissatisfaction 6 months after surgery, based on their WORQ score. That is, patients who expected to be dissatisfied before their surgery had approximately five times greater odds of being dissatisfied after their surgery than did those who expected to be satisfied with their ability to do knee-straining activities at work (odds ratio, 5.1; 95% confidence interval, 1.7-15.5). Among those with a WORQ score of 40, indicating a greater expectation of difficulty using their knees postoperatively, 55% were dissatisfied after their surgery, compared with 19% of those with a WORQ score of 85, who expected greater knee ability after their surgery.

The other factors that the researchers examined, which had no effect on WORQ scores, included age, sex, BMI, education, comorbidities, KOOS pain subscale, having a knee-straining job, having needed surgery because of work, or having preoperative sick leave.

One discussion prompted by the presentation focused specifically on individuals’ ability to kneel without much difficulty after their surgery, an activity that’s not typically considered likely, Ms. van Zaanen noted. One audience member, Gillian Hawker, MD, MSc, a professor of medicine in the division of rheumatology at the University of Toronto, questioned whether the field should accept that current reality from surgical intervention. Dr. Hawker described a cohort she had analyzed in which two-thirds of the participants had expected they would be able to kneel after their surgery, regardless of whether it was related to work or other activities.

“Kneeling is important, not just for work; it’s important for culture and religion and lots of other things,” Dr. Hawker said. “How will you help these people to kneel after knee replacement when the surgery isn’t really performed to enable people to do that?” In response, Ms. van Zaanen noted it might not be achievable, as the research literature demonstrates, but Dr. Hawker suggested that is itself problematic.

“I guess what I’m asking is, why are we settling for that? If it’s important to so many people, and an expectation of so many people, why don’t we technologically improve such that, post arthroplasty, people can kneel?”

Another commenter suggested that the study’s findings may not indicate a need to manage patients’ expectations prior to surgery so much as showing that some patients simply have realistic expectations of what they will and will not be able to do after knee replacement.

“Is it possible that people who had low expectations – those who expected to be dissatisfied afterwards – were appropriately understanding that they were likely to be dissatisfied afterwards, in which case, managing their expectations might do nothing for their dissatisfaction afterwards?” the commenter asked. It is likely necessary to conduct additional research about expectations before surgery and experiences after surgery to address that question, Ms. van Zaanen suggested.

Ms. van Zaanen and Dr. Hawker reported having no relevant financial relationships. The presentation did not note any external funding. The Congress was sponsored by the Osteoarthritis Research Society International.

NEW ORLEANS – A monoclonal antibody targeting interferon-beta (IFN-beta) provided substantial reductions in the skin lesions associated with dermatomyositis in a double-blind, placebo-controlled phase 2 trial, according to results presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

“These findings support the inhibition of IFN-beta as a promising therapeutic strategy in skin-predominant disease,” said principal investigator Aaron Mangold, MD, associate professor of dermatology, Mayo Clinic, Scottsdale, Ariz.

Ted Bosworth/MDedge News

Dermatomyositis, a rare autoimmune inflammatory condition that typically involves both skeletal muscles and skin, is a challenging disease with a diverse set of potential complications.

Immunosuppressive and immunomodulatory agents are used with mixed success for myositis, but skin manifestations, which include papular eruptions, heliotrope rash, photoerythema, burning, and pruritus, are often the most troublesome and the most difficult to control. Treatment options other than immunomodulators that target cutaneous involvement – which include steroids, emollients, and photoprotection – are generally modestly effective, according to Dr. Mangold.
 

Targeting an elevated cytokine

Interest in IFN-beta, which is elevated in the blood of individuals with dermatomyositis, was triggered by evidence that this cytokine plays an important role in driving the skin inflammation, Dr. Mangold explained.

“The blood concentrations of IFN-beta are positively correlated with cutaneous disease activity and severity,” he said.

The study drug, currently known as PF-06823859 (Dazukibart), “is a potent, selective humanized IgG1-neutralizing antibody directed at IFN-beta,” Dr. Mangold said. A dose-ranging phase 1 study published 2 years ago provided evidence of acceptable pharmacokinetics and safety in healthy individuals to support treatment studies for disorders associated with elevated IFN-beta levels. In addition to dermatomyositis, this includes systemic lupus erythematosus.

In this phase 2 trial, patients whose condition was not improved by at least one standard-care therapy for skin manifestations of dermatomyositis were eligible if they had moderate to severe disease as measured with the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), according to Dr. Mangold. During the study, patients were allowed to remain on a disease modifying antirheumatic drug and/or prednisone if they had been on stable doses and did not change the dose.

Richard Usatine, MD

After a screening run-in, the trial had two blinded stages. In stage 1, 30 patients were randomly assigned either to 600 mg of PF-06823859 or to placebo, both administered intravenously every 4 weeks. A second cohort of 25 patients was randomly assigned in stage 2 to placebo, 150 mg of PF-06823859, or 600 mg of PF-06823859. The primary endpoint assessed at 12 weeks was a greater than 5-point reduction in CDASI score or greater than 40% CDASI improvement from baseline.

Both endpoints are associated with a clinically meaningful response in regard to an improved quality of life, Dr. Mangold noted.
 

Both doses better than placebo

In results from the stage 1 portion, the mean reduction in CDASI at 12 weeks after three doses of the assigned therapy was 18.8 points in the active-treatment group versus 3.9 points in the placebo group. In pooled data from stage 1 and 2, the reductions were 16.6 points, 19.2 points, and 2.9 points for the 150-mg, 600-mg, and placebo arms, respectively. Both doses achieved a highly significant advantage over placebo.

For both stages and doses, the response curves of the active-treatment groups and the placebo group diverged almost immediately. By 4 weeks, both measures of CDASI reductions on active therapy were significantly improved relative to placebo, and the response curves had a consistent downward slope through the end of the 12-week study, Dr. Mangold reported.

The majority of patients responded by either of the primary endpoint criteria. For a CDASI reduction of greater than 5 points, the response rates were 100% and 96% for the 150-mg and 600-mg doses of PF-06823859, respectively. The placebo response was 35.7%. For the CDASI reduction of greater than 40%, the rates were 80%, 82.1%, and 7.1% for the 150-mg, 600-mg, and placebo arms, respectively.

“There were no major safety concerns. Most of the treatment-emergent adverse events were mild, and adverse events did not have a relationship to dose,” Dr. Mangold said. Notably, there were no cases of herpes zoster, and infections of any kind were low in all study groups.

A phase 3 study is being planned with the 600-mg dose, according to Dr. Mangold, but he acknowledged that regulatory authorities have generally required endpoints for both cutaneous and muscle manifestations in previous trials of therapies for dermatomyositis.

It is not yet certain that “there will be a carve-out for skin,” he said in answer to a question about investigations moving forward. So far, studies have been focused on skin response. However, a meaningful degree of benefit against muscle involvement, which has not yet been well studied, has not been ruled out.

Even though this is a phase 2 trial with small numbers, it was controlled and blinded, and the potential of an inhibitor of IFN-beta to control the skin manifestations of dermatomyositis “is kind of a big deal,” said Paul Nghiem, MD, PhD, professor of dermatology, University of Washington, Seattle.

“There is definitely an unmet need for better therapies to control the skin involvement,” Dr. Nghiem said.

Hensin Tsao, MD, PhD, clinical director of the Melanoma and Pigmented Lesion Center at Massachusetts General Hospital, Boston, agreed. Like Dr. Nghiem, Dr. Tsao was a panelist during the late-breaker session where the study was presented, and he was impressed by the data.

“This is something that is definitely newsworthy,” Dr. Tsao said.

Dr. Mangold reports financial relationships with Actelion, Amgen, Corbus, Eli Lilly, Incyte, miRagen, Novartis, Regeneron, Solagenix, Sun Pharmaceuticals, Teva, and Pfizer, which provided funding for this trial. Both Dr. Nghiem and Dr. Tsao reported no relevant financial relationships.

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

NEW ORLEANS – A monoclonal antibody targeting interferon-beta (IFN-beta) provided substantial reductions in the skin lesions associated with dermatomyositis in a double-blind, placebo-controlled phase 2 trial, according to results presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

“These findings support the inhibition of IFN-beta as a promising therapeutic strategy in skin-predominant disease,” said principal investigator Aaron Mangold, MD, associate professor of dermatology, Mayo Clinic, Scottsdale, Ariz.

Ted Bosworth/MDedge News

Dermatomyositis, a rare autoimmune inflammatory condition that typically involves both skeletal muscles and skin, is a challenging disease with a diverse set of potential complications.

Immunosuppressive and immunomodulatory agents are used with mixed success for myositis, but skin manifestations, which include papular eruptions, heliotrope rash, photoerythema, burning, and pruritus, are often the most troublesome and the most difficult to control. Treatment options other than immunomodulators that target cutaneous involvement – which include steroids, emollients, and photoprotection – are generally modestly effective, according to Dr. Mangold.
 

Targeting an elevated cytokine

Interest in IFN-beta, which is elevated in the blood of individuals with dermatomyositis, was triggered by evidence that this cytokine plays an important role in driving the skin inflammation, Dr. Mangold explained.

“The blood concentrations of IFN-beta are positively correlated with cutaneous disease activity and severity,” he said.

The study drug, currently known as PF-06823859 (Dazukibart), “is a potent, selective humanized IgG1-neutralizing antibody directed at IFN-beta,” Dr. Mangold said. A dose-ranging phase 1 study published 2 years ago provided evidence of acceptable pharmacokinetics and safety in healthy individuals to support treatment studies for disorders associated with elevated IFN-beta levels. In addition to dermatomyositis, this includes systemic lupus erythematosus.

In this phase 2 trial, patients whose condition was not improved by at least one standard-care therapy for skin manifestations of dermatomyositis were eligible if they had moderate to severe disease as measured with the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), according to Dr. Mangold. During the study, patients were allowed to remain on a disease modifying antirheumatic drug and/or prednisone if they had been on stable doses and did not change the dose.

Richard Usatine, MD

After a screening run-in, the trial had two blinded stages. In stage 1, 30 patients were randomly assigned either to 600 mg of PF-06823859 or to placebo, both administered intravenously every 4 weeks. A second cohort of 25 patients was randomly assigned in stage 2 to placebo, 150 mg of PF-06823859, or 600 mg of PF-06823859. The primary endpoint assessed at 12 weeks was a greater than 5-point reduction in CDASI score or greater than 40% CDASI improvement from baseline.

Both endpoints are associated with a clinically meaningful response in regard to an improved quality of life, Dr. Mangold noted.
 

Both doses better than placebo

In results from the stage 1 portion, the mean reduction in CDASI at 12 weeks after three doses of the assigned therapy was 18.8 points in the active-treatment group versus 3.9 points in the placebo group. In pooled data from stage 1 and 2, the reductions were 16.6 points, 19.2 points, and 2.9 points for the 150-mg, 600-mg, and placebo arms, respectively. Both doses achieved a highly significant advantage over placebo.

For both stages and doses, the response curves of the active-treatment groups and the placebo group diverged almost immediately. By 4 weeks, both measures of CDASI reductions on active therapy were significantly improved relative to placebo, and the response curves had a consistent downward slope through the end of the 12-week study, Dr. Mangold reported.

The majority of patients responded by either of the primary endpoint criteria. For a CDASI reduction of greater than 5 points, the response rates were 100% and 96% for the 150-mg and 600-mg doses of PF-06823859, respectively. The placebo response was 35.7%. For the CDASI reduction of greater than 40%, the rates were 80%, 82.1%, and 7.1% for the 150-mg, 600-mg, and placebo arms, respectively.

“There were no major safety concerns. Most of the treatment-emergent adverse events were mild, and adverse events did not have a relationship to dose,” Dr. Mangold said. Notably, there were no cases of herpes zoster, and infections of any kind were low in all study groups.

A phase 3 study is being planned with the 600-mg dose, according to Dr. Mangold, but he acknowledged that regulatory authorities have generally required endpoints for both cutaneous and muscle manifestations in previous trials of therapies for dermatomyositis.

It is not yet certain that “there will be a carve-out for skin,” he said in answer to a question about investigations moving forward. So far, studies have been focused on skin response. However, a meaningful degree of benefit against muscle involvement, which has not yet been well studied, has not been ruled out.

Even though this is a phase 2 trial with small numbers, it was controlled and blinded, and the potential of an inhibitor of IFN-beta to control the skin manifestations of dermatomyositis “is kind of a big deal,” said Paul Nghiem, MD, PhD, professor of dermatology, University of Washington, Seattle.

“There is definitely an unmet need for better therapies to control the skin involvement,” Dr. Nghiem said.

Hensin Tsao, MD, PhD, clinical director of the Melanoma and Pigmented Lesion Center at Massachusetts General Hospital, Boston, agreed. Like Dr. Nghiem, Dr. Tsao was a panelist during the late-breaker session where the study was presented, and he was impressed by the data.

“This is something that is definitely newsworthy,” Dr. Tsao said.

Dr. Mangold reports financial relationships with Actelion, Amgen, Corbus, Eli Lilly, Incyte, miRagen, Novartis, Regeneron, Solagenix, Sun Pharmaceuticals, Teva, and Pfizer, which provided funding for this trial. Both Dr. Nghiem and Dr. Tsao reported no relevant financial relationships.

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

NEW ORLEANS – A monoclonal antibody targeting interferon-beta (IFN-beta) provided substantial reductions in the skin lesions associated with dermatomyositis in a double-blind, placebo-controlled phase 2 trial, according to results presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

“These findings support the inhibition of IFN-beta as a promising therapeutic strategy in skin-predominant disease,” said principal investigator Aaron Mangold, MD, associate professor of dermatology, Mayo Clinic, Scottsdale, Ariz.

Ted Bosworth/MDedge News

Dermatomyositis, a rare autoimmune inflammatory condition that typically involves both skeletal muscles and skin, is a challenging disease with a diverse set of potential complications.

Immunosuppressive and immunomodulatory agents are used with mixed success for myositis, but skin manifestations, which include papular eruptions, heliotrope rash, photoerythema, burning, and pruritus, are often the most troublesome and the most difficult to control. Treatment options other than immunomodulators that target cutaneous involvement – which include steroids, emollients, and photoprotection – are generally modestly effective, according to Dr. Mangold.
 

Targeting an elevated cytokine

Interest in IFN-beta, which is elevated in the blood of individuals with dermatomyositis, was triggered by evidence that this cytokine plays an important role in driving the skin inflammation, Dr. Mangold explained.

“The blood concentrations of IFN-beta are positively correlated with cutaneous disease activity and severity,” he said.

The study drug, currently known as PF-06823859 (Dazukibart), “is a potent, selective humanized IgG1-neutralizing antibody directed at IFN-beta,” Dr. Mangold said. A dose-ranging phase 1 study published 2 years ago provided evidence of acceptable pharmacokinetics and safety in healthy individuals to support treatment studies for disorders associated with elevated IFN-beta levels. In addition to dermatomyositis, this includes systemic lupus erythematosus.

In this phase 2 trial, patients whose condition was not improved by at least one standard-care therapy for skin manifestations of dermatomyositis were eligible if they had moderate to severe disease as measured with the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), according to Dr. Mangold. During the study, patients were allowed to remain on a disease modifying antirheumatic drug and/or prednisone if they had been on stable doses and did not change the dose.

Richard Usatine, MD

After a screening run-in, the trial had two blinded stages. In stage 1, 30 patients were randomly assigned either to 600 mg of PF-06823859 or to placebo, both administered intravenously every 4 weeks. A second cohort of 25 patients was randomly assigned in stage 2 to placebo, 150 mg of PF-06823859, or 600 mg of PF-06823859. The primary endpoint assessed at 12 weeks was a greater than 5-point reduction in CDASI score or greater than 40% CDASI improvement from baseline.

Both endpoints are associated with a clinically meaningful response in regard to an improved quality of life, Dr. Mangold noted.
 

Both doses better than placebo

In results from the stage 1 portion, the mean reduction in CDASI at 12 weeks after three doses of the assigned therapy was 18.8 points in the active-treatment group versus 3.9 points in the placebo group. In pooled data from stage 1 and 2, the reductions were 16.6 points, 19.2 points, and 2.9 points for the 150-mg, 600-mg, and placebo arms, respectively. Both doses achieved a highly significant advantage over placebo.

For both stages and doses, the response curves of the active-treatment groups and the placebo group diverged almost immediately. By 4 weeks, both measures of CDASI reductions on active therapy were significantly improved relative to placebo, and the response curves had a consistent downward slope through the end of the 12-week study, Dr. Mangold reported.

The majority of patients responded by either of the primary endpoint criteria. For a CDASI reduction of greater than 5 points, the response rates were 100% and 96% for the 150-mg and 600-mg doses of PF-06823859, respectively. The placebo response was 35.7%. For the CDASI reduction of greater than 40%, the rates were 80%, 82.1%, and 7.1% for the 150-mg, 600-mg, and placebo arms, respectively.

“There were no major safety concerns. Most of the treatment-emergent adverse events were mild, and adverse events did not have a relationship to dose,” Dr. Mangold said. Notably, there were no cases of herpes zoster, and infections of any kind were low in all study groups.

A phase 3 study is being planned with the 600-mg dose, according to Dr. Mangold, but he acknowledged that regulatory authorities have generally required endpoints for both cutaneous and muscle manifestations in previous trials of therapies for dermatomyositis.

It is not yet certain that “there will be a carve-out for skin,” he said in answer to a question about investigations moving forward. So far, studies have been focused on skin response. However, a meaningful degree of benefit against muscle involvement, which has not yet been well studied, has not been ruled out.

Even though this is a phase 2 trial with small numbers, it was controlled and blinded, and the potential of an inhibitor of IFN-beta to control the skin manifestations of dermatomyositis “is kind of a big deal,” said Paul Nghiem, MD, PhD, professor of dermatology, University of Washington, Seattle.

“There is definitely an unmet need for better therapies to control the skin involvement,” Dr. Nghiem said.

Hensin Tsao, MD, PhD, clinical director of the Melanoma and Pigmented Lesion Center at Massachusetts General Hospital, Boston, agreed. Like Dr. Nghiem, Dr. Tsao was a panelist during the late-breaker session where the study was presented, and he was impressed by the data.

“This is something that is definitely newsworthy,” Dr. Tsao said.

Dr. Mangold reports financial relationships with Actelion, Amgen, Corbus, Eli Lilly, Incyte, miRagen, Novartis, Regeneron, Solagenix, Sun Pharmaceuticals, Teva, and Pfizer, which provided funding for this trial. Both Dr. Nghiem and Dr. Tsao reported no relevant financial relationships.

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

DENVER – Initiating exercise therapy early on in people who develop symptoms of knee osteoarthritis – even within their first year of pain or reduced function – is associated with modestly lower pain scores and modestly better function than in those whose symptoms have lasted longer, according to a study presented at the OARSI 2023 World Congress.

Although the benefits of exercise therapy for advanced knee osteoarthritis had already been well established, this study looked specifically at benefits from exercise therapy earlier on, in patients with a shorter duration of symptoms.

“Exercise indeed seems especially beneficial in patients with shorter symptom duration and should therefore be encouraged at first symptom presentation,” Marienke van Middelkoop, PhD, of Erasmus MC Medical University in Rotterdam, the Netherlands, told attendees at the meeting, sponsored by Osteoarthritis Research Society International. “It is, however, still a challenge how we can identify patients but also how we can motivate these patients with early symptoms of osteoarthritis.” She noted that a separate pilot study had experienced difficulty recruiting people with short-term symptom duration.

The researchers compared the effect of exercise therapy and no exercise among adults at least 45 years old with knee osteoarthritis, relying on individual participant data from the STEER OA study, a meta-analysis of 31 studies that involved 4,241 participants. After excluding studies that didn’t report symptom duration, lacked a control group or consent, or focused on hip osteoarthritis, the researchers ended up with 10 studies involving 1,895 participants. These participants were stratified based on the duration of their symptoms: up to 1 year (14.4%), 1-2 years (11%), and 2 years or longer (74%).

About two-thirds of the participants were women (65.9%), with an average age of 65 years and an average body mass index (BMI) of 30.7 kg/m². Any land-based or water-based therapeutic exercise counted for the 62% of participants in the intervention group, while the control group had no exercise. Outcomes were assessed based on self-reported pain or physical function at short-term and long-term follow-up, which were as close as possible to 3 months for short-term and the closest date to 12 months for longer term. At baseline, the participants reported an average pain score of 41.7 on a 0-to-100 scale and an average physical function score of 37.4 on a 0-to-100 scale where lower scores indicate better function.

Among those doing exercise therapy, average pain scores dropped 4.56 points in the short term and 7.43 points in the long term. Short-term and long-term pain scores were lower among those whose symptom durations were shorter. For example, those with symptoms for less than a year reported a short-term pain score of 29, compared with 30 for those with 1-2 years of pain and 32 for those with at least 2 years of pain. Results were similar for long-term pain (a score of 26, compared with 28 and 33, respectively).

Participants engaging in exercise therapy also improved average function scores, with a pattern of improvement that was similar to pain scores based on patients’ symptom duration. The average short-term function score was 26 among those with less than a year of symptoms, compared with 28 for those with symptoms for 1-2 years, and 30 for those with symptoms for at least 2 years. Longer-term function scores were 21, 24, and 29, respectively, based on increasing symptom durations.

Chris Yun Lane, PT, DPT, a physical therapist and a fourth-year PhD student at the University of North Carolina at Chapel Hill, was not surprised at the exercise benefit given the extensive evidence already showing that exercise is beneficial for patients with osteoarthritis whose symptoms have lasted longer.

“Just spending a little bit of time on education, designing kind of simple exercise programs, such as walking programs, can be very helpful,” Dr. Lane said in an interview. “Of course, some of it is dependent on the patient itself, but strengthening range of motion is often very helpful.” Dr. Lane said it’s particularly important for physicians and physical therapists to emphasize the importance of exercise to their patients because that guidance doesn’t always occur as often as it should.

Ron Ellis Jr., DO, MBA, chief strategy officer of Pacira BioSciences in Tampa, Fla., noted that a lot of patients with knee osteoarthritis have weakness in their quads, so quad strengthening is “a typical part of our improvement program for patients with osteoarthritis,” he said in an interview. Dr. Ellis also referenced a session he attended the previous day that showed exercise results in reduced inflammation.

“So you may not have weight loss, but you can lower the inflammatory state of the overall body and of the specific joints,” Dr. Ellis said, “so that would support [this study’s] conclusion.”

The STEER OA study was funded by the Chartered Society of Physiotherapy Charitable Trust and the National Institute for Health Research School of Primary Care Research. Dr. van Middelkoop and Dr. Lane both reported having no relevant financial relationships.

DENVER – Initiating exercise therapy early on in people who develop symptoms of knee osteoarthritis – even within their first year of pain or reduced function – is associated with modestly lower pain scores and modestly better function than in those whose symptoms have lasted longer, according to a study presented at the OARSI 2023 World Congress.

Although the benefits of exercise therapy for advanced knee osteoarthritis had already been well established, this study looked specifically at benefits from exercise therapy earlier on, in patients with a shorter duration of symptoms.

“Exercise indeed seems especially beneficial in patients with shorter symptom duration and should therefore be encouraged at first symptom presentation,” Marienke van Middelkoop, PhD, of Erasmus MC Medical University in Rotterdam, the Netherlands, told attendees at the meeting, sponsored by Osteoarthritis Research Society International. “It is, however, still a challenge how we can identify patients but also how we can motivate these patients with early symptoms of osteoarthritis.” She noted that a separate pilot study had experienced difficulty recruiting people with short-term symptom duration.

The researchers compared the effect of exercise therapy and no exercise among adults at least 45 years old with knee osteoarthritis, relying on individual participant data from the STEER OA study, a meta-analysis of 31 studies that involved 4,241 participants. After excluding studies that didn’t report symptom duration, lacked a control group or consent, or focused on hip osteoarthritis, the researchers ended up with 10 studies involving 1,895 participants. These participants were stratified based on the duration of their symptoms: up to 1 year (14.4%), 1-2 years (11%), and 2 years or longer (74%).

About two-thirds of the participants were women (65.9%), with an average age of 65 years and an average body mass index (BMI) of 30.7 kg/m². Any land-based or water-based therapeutic exercise counted for the 62% of participants in the intervention group, while the control group had no exercise. Outcomes were assessed based on self-reported pain or physical function at short-term and long-term follow-up, which were as close as possible to 3 months for short-term and the closest date to 12 months for longer term. At baseline, the participants reported an average pain score of 41.7 on a 0-to-100 scale and an average physical function score of 37.4 on a 0-to-100 scale where lower scores indicate better function.

Among those doing exercise therapy, average pain scores dropped 4.56 points in the short term and 7.43 points in the long term. Short-term and long-term pain scores were lower among those whose symptom durations were shorter. For example, those with symptoms for less than a year reported a short-term pain score of 29, compared with 30 for those with 1-2 years of pain and 32 for those with at least 2 years of pain. Results were similar for long-term pain (a score of 26, compared with 28 and 33, respectively).

Participants engaging in exercise therapy also improved average function scores, with a pattern of improvement that was similar to pain scores based on patients’ symptom duration. The average short-term function score was 26 among those with less than a year of symptoms, compared with 28 for those with symptoms for 1-2 years, and 30 for those with symptoms for at least 2 years. Longer-term function scores were 21, 24, and 29, respectively, based on increasing symptom durations.

Chris Yun Lane, PT, DPT, a physical therapist and a fourth-year PhD student at the University of North Carolina at Chapel Hill, was not surprised at the exercise benefit given the extensive evidence already showing that exercise is beneficial for patients with osteoarthritis whose symptoms have lasted longer.

“Just spending a little bit of time on education, designing kind of simple exercise programs, such as walking programs, can be very helpful,” Dr. Lane said in an interview. “Of course, some of it is dependent on the patient itself, but strengthening range of motion is often very helpful.” Dr. Lane said it’s particularly important for physicians and physical therapists to emphasize the importance of exercise to their patients because that guidance doesn’t always occur as often as it should.

Ron Ellis Jr., DO, MBA, chief strategy officer of Pacira BioSciences in Tampa, Fla., noted that a lot of patients with knee osteoarthritis have weakness in their quads, so quad strengthening is “a typical part of our improvement program for patients with osteoarthritis,” he said in an interview. Dr. Ellis also referenced a session he attended the previous day that showed exercise results in reduced inflammation.

“So you may not have weight loss, but you can lower the inflammatory state of the overall body and of the specific joints,” Dr. Ellis said, “so that would support [this study’s] conclusion.”

The STEER OA study was funded by the Chartered Society of Physiotherapy Charitable Trust and the National Institute for Health Research School of Primary Care Research. Dr. van Middelkoop and Dr. Lane both reported having no relevant financial relationships.

DENVER – Initiating exercise therapy early on in people who develop symptoms of knee osteoarthritis – even within their first year of pain or reduced function – is associated with modestly lower pain scores and modestly better function than in those whose symptoms have lasted longer, according to a study presented at the OARSI 2023 World Congress.

Although the benefits of exercise therapy for advanced knee osteoarthritis had already been well established, this study looked specifically at benefits from exercise therapy earlier on, in patients with a shorter duration of symptoms.

“Exercise indeed seems especially beneficial in patients with shorter symptom duration and should therefore be encouraged at first symptom presentation,” Marienke van Middelkoop, PhD, of Erasmus MC Medical University in Rotterdam, the Netherlands, told attendees at the meeting, sponsored by Osteoarthritis Research Society International. “It is, however, still a challenge how we can identify patients but also how we can motivate these patients with early symptoms of osteoarthritis.” She noted that a separate pilot study had experienced difficulty recruiting people with short-term symptom duration.

The researchers compared the effect of exercise therapy and no exercise among adults at least 45 years old with knee osteoarthritis, relying on individual participant data from the STEER OA study, a meta-analysis of 31 studies that involved 4,241 participants. After excluding studies that didn’t report symptom duration, lacked a control group or consent, or focused on hip osteoarthritis, the researchers ended up with 10 studies involving 1,895 participants. These participants were stratified based on the duration of their symptoms: up to 1 year (14.4%), 1-2 years (11%), and 2 years or longer (74%).

About two-thirds of the participants were women (65.9%), with an average age of 65 years and an average body mass index (BMI) of 30.7 kg/m². Any land-based or water-based therapeutic exercise counted for the 62% of participants in the intervention group, while the control group had no exercise. Outcomes were assessed based on self-reported pain or physical function at short-term and long-term follow-up, which were as close as possible to 3 months for short-term and the closest date to 12 months for longer term. At baseline, the participants reported an average pain score of 41.7 on a 0-to-100 scale and an average physical function score of 37.4 on a 0-to-100 scale where lower scores indicate better function.

Among those doing exercise therapy, average pain scores dropped 4.56 points in the short term and 7.43 points in the long term. Short-term and long-term pain scores were lower among those whose symptom durations were shorter. For example, those with symptoms for less than a year reported a short-term pain score of 29, compared with 30 for those with 1-2 years of pain and 32 for those with at least 2 years of pain. Results were similar for long-term pain (a score of 26, compared with 28 and 33, respectively).

Participants engaging in exercise therapy also improved average function scores, with a pattern of improvement that was similar to pain scores based on patients’ symptom duration. The average short-term function score was 26 among those with less than a year of symptoms, compared with 28 for those with symptoms for 1-2 years, and 30 for those with symptoms for at least 2 years. Longer-term function scores were 21, 24, and 29, respectively, based on increasing symptom durations.

Chris Yun Lane, PT, DPT, a physical therapist and a fourth-year PhD student at the University of North Carolina at Chapel Hill, was not surprised at the exercise benefit given the extensive evidence already showing that exercise is beneficial for patients with osteoarthritis whose symptoms have lasted longer.

“Just spending a little bit of time on education, designing kind of simple exercise programs, such as walking programs, can be very helpful,” Dr. Lane said in an interview. “Of course, some of it is dependent on the patient itself, but strengthening range of motion is often very helpful.” Dr. Lane said it’s particularly important for physicians and physical therapists to emphasize the importance of exercise to their patients because that guidance doesn’t always occur as often as it should.

Ron Ellis Jr., DO, MBA, chief strategy officer of Pacira BioSciences in Tampa, Fla., noted that a lot of patients with knee osteoarthritis have weakness in their quads, so quad strengthening is “a typical part of our improvement program for patients with osteoarthritis,” he said in an interview. Dr. Ellis also referenced a session he attended the previous day that showed exercise results in reduced inflammation.

“So you may not have weight loss, but you can lower the inflammatory state of the overall body and of the specific joints,” Dr. Ellis said, “so that would support [this study’s] conclusion.”

The STEER OA study was funded by the Chartered Society of Physiotherapy Charitable Trust and the National Institute for Health Research School of Primary Care Research. Dr. van Middelkoop and Dr. Lane both reported having no relevant financial relationships.

Air pollution appears to contribute independently to bone damage in postmenopausal women, new data suggest.

The findings come from a new analysis of data from the Women’s Health Initiative (WHI) and location-specific air particulate information from the U.S. Environmental Protection Agency.

copyright Sergiy Serdyuk/istockphoto.com

“Our findings confirm that poor air quality may be a risk factor for bone loss, independent of socioeconomic or demographic factors, and expands previous findings to postmenopausal women. Indeed, to our knowledge, this is the first study of the impact of criteria air pollutants on bone health in postmenopausal women,” Diddier Prada, MD, PhD, Columbia University, New York, and colleagues wrote.

The results are also the first to show that “nitrogen oxides contribute the most to bone damage and that the lumbar spine is one of the most susceptible sites,” they added.

Public health policies should aim to reduce air pollution in general, they wrote, and reducing nitrogen oxides, in particular, will reduce bone damage in postmenopausal women, prevent bone fractures, and reduce the health cost burden associated with osteoporosis in this population.

The findings were recently published in eClinicalMedicine.

Asked to comment, Giovanni Adami, MD, PhD, said in an interview that the study “adds to the body of literature on air pollution and bone health. The study confirms and provides further evidence linking air pollution exposure and osteoporosis.”

Dr. Adami, of the University of Verona (Italy), who also studies this topic, said that these new findings align with those from his group and others.

“The scientific literature in the field is clearly pointing toward a negative effect of chronic pollution exposure on bone health.”

He pointed to one study from his group that found chronic exposure to ultrafine particulate matter is associated with low BMD, and consequently, bone fragility, and another study that showed acute exposure to high levels of pollutants could actually cause fractures.

As for what might be done clinically, Dr. Adami said: “It is difficult to extrapolate direct and immediate recommendations for patients.

“However, it might be acceptable to say that patients at risk of osteoporosis, such as older women or those with prior bone fractures, should avoid chronic exposure to air pollution, perhaps using masks when walking in traffic or using air filters for indoor ventilation.”

Dr. Adami also said that this evidence so far might spur the future inclusion of chronic exposure to air pollution in fracture risk assessment tools, although this isn’t likely to come about in the near future.
 

Particulates linked to whole-body, hip, lumbar, and femoral neck BMD

The prospective observational study included 9,041 WHI participants seen over 32,663 visits who were an average of 63 years old at baseline. More than 70% were White, and just under half were college graduates.

With geocoded address data used to estimate particulate matter concentrations, mean levels of particulate matter of 10 mcm or less, nitrogen oxide nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years were all negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD.

In the multivariate analysis, the highest correlations were found between nitrogen oxide and nitrogen dioxide. For example, lumbar spine BMD decreased by 0.026 g/cm² per year per 10% increase in 3-year mean nitrogen dioxide concentration.

“Our findings show that both particulate matter and gases may adversely impact BMD and that nitrogen oxides may play a critical role in bone damage and osteoporosis risk,” Dr. Prada and colleagues wrote.

Dr. Adami added: “We need more data to understand the precise magnitude of effect of air pollution on fractures, which might depend on levels of exposure but also on genetics and lifestyle.”

The study was funded by the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Adami reported receiving fees from Amgen, Eli Lilly, UCB, Fresenius Kabi, Galapagos, and Theramex.

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

Air pollution appears to contribute independently to bone damage in postmenopausal women, new data suggest.

The findings come from a new analysis of data from the Women’s Health Initiative (WHI) and location-specific air particulate information from the U.S. Environmental Protection Agency.

copyright Sergiy Serdyuk/istockphoto.com

“Our findings confirm that poor air quality may be a risk factor for bone loss, independent of socioeconomic or demographic factors, and expands previous findings to postmenopausal women. Indeed, to our knowledge, this is the first study of the impact of criteria air pollutants on bone health in postmenopausal women,” Diddier Prada, MD, PhD, Columbia University, New York, and colleagues wrote.

The results are also the first to show that “nitrogen oxides contribute the most to bone damage and that the lumbar spine is one of the most susceptible sites,” they added.

Public health policies should aim to reduce air pollution in general, they wrote, and reducing nitrogen oxides, in particular, will reduce bone damage in postmenopausal women, prevent bone fractures, and reduce the health cost burden associated with osteoporosis in this population.

The findings were recently published in eClinicalMedicine.

Asked to comment, Giovanni Adami, MD, PhD, said in an interview that the study “adds to the body of literature on air pollution and bone health. The study confirms and provides further evidence linking air pollution exposure and osteoporosis.”

Dr. Adami, of the University of Verona (Italy), who also studies this topic, said that these new findings align with those from his group and others.

“The scientific literature in the field is clearly pointing toward a negative effect of chronic pollution exposure on bone health.”

He pointed to one study from his group that found chronic exposure to ultrafine particulate matter is associated with low BMD, and consequently, bone fragility, and another study that showed acute exposure to high levels of pollutants could actually cause fractures.

As for what might be done clinically, Dr. Adami said: “It is difficult to extrapolate direct and immediate recommendations for patients.

“However, it might be acceptable to say that patients at risk of osteoporosis, such as older women or those with prior bone fractures, should avoid chronic exposure to air pollution, perhaps using masks when walking in traffic or using air filters for indoor ventilation.”

Dr. Adami also said that this evidence so far might spur the future inclusion of chronic exposure to air pollution in fracture risk assessment tools, although this isn’t likely to come about in the near future.
 

Particulates linked to whole-body, hip, lumbar, and femoral neck BMD

The prospective observational study included 9,041 WHI participants seen over 32,663 visits who were an average of 63 years old at baseline. More than 70% were White, and just under half were college graduates.

With geocoded address data used to estimate particulate matter concentrations, mean levels of particulate matter of 10 mcm or less, nitrogen oxide nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years were all negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD.

In the multivariate analysis, the highest correlations were found between nitrogen oxide and nitrogen dioxide. For example, lumbar spine BMD decreased by 0.026 g/cm² per year per 10% increase in 3-year mean nitrogen dioxide concentration.

“Our findings show that both particulate matter and gases may adversely impact BMD and that nitrogen oxides may play a critical role in bone damage and osteoporosis risk,” Dr. Prada and colleagues wrote.

Dr. Adami added: “We need more data to understand the precise magnitude of effect of air pollution on fractures, which might depend on levels of exposure but also on genetics and lifestyle.”

The study was funded by the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Adami reported receiving fees from Amgen, Eli Lilly, UCB, Fresenius Kabi, Galapagos, and Theramex.

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

Air pollution appears to contribute independently to bone damage in postmenopausal women, new data suggest.

The findings come from a new analysis of data from the Women’s Health Initiative (WHI) and location-specific air particulate information from the U.S. Environmental Protection Agency.

copyright Sergiy Serdyuk/istockphoto.com

“Our findings confirm that poor air quality may be a risk factor for bone loss, independent of socioeconomic or demographic factors, and expands previous findings to postmenopausal women. Indeed, to our knowledge, this is the first study of the impact of criteria air pollutants on bone health in postmenopausal women,” Diddier Prada, MD, PhD, Columbia University, New York, and colleagues wrote.

The results are also the first to show that “nitrogen oxides contribute the most to bone damage and that the lumbar spine is one of the most susceptible sites,” they added.

Public health policies should aim to reduce air pollution in general, they wrote, and reducing nitrogen oxides, in particular, will reduce bone damage in postmenopausal women, prevent bone fractures, and reduce the health cost burden associated with osteoporosis in this population.

The findings were recently published in eClinicalMedicine.

Asked to comment, Giovanni Adami, MD, PhD, said in an interview that the study “adds to the body of literature on air pollution and bone health. The study confirms and provides further evidence linking air pollution exposure and osteoporosis.”

Dr. Adami, of the University of Verona (Italy), who also studies this topic, said that these new findings align with those from his group and others.

“The scientific literature in the field is clearly pointing toward a negative effect of chronic pollution exposure on bone health.”

He pointed to one study from his group that found chronic exposure to ultrafine particulate matter is associated with low BMD, and consequently, bone fragility, and another study that showed acute exposure to high levels of pollutants could actually cause fractures.

As for what might be done clinically, Dr. Adami said: “It is difficult to extrapolate direct and immediate recommendations for patients.

“However, it might be acceptable to say that patients at risk of osteoporosis, such as older women or those with prior bone fractures, should avoid chronic exposure to air pollution, perhaps using masks when walking in traffic or using air filters for indoor ventilation.”

Dr. Adami also said that this evidence so far might spur the future inclusion of chronic exposure to air pollution in fracture risk assessment tools, although this isn’t likely to come about in the near future.
 

Particulates linked to whole-body, hip, lumbar, and femoral neck BMD

The prospective observational study included 9,041 WHI participants seen over 32,663 visits who were an average of 63 years old at baseline. More than 70% were White, and just under half were college graduates.

With geocoded address data used to estimate particulate matter concentrations, mean levels of particulate matter of 10 mcm or less, nitrogen oxide nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years were all negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD.

In the multivariate analysis, the highest correlations were found between nitrogen oxide and nitrogen dioxide. For example, lumbar spine BMD decreased by 0.026 g/cm² per year per 10% increase in 3-year mean nitrogen dioxide concentration.

“Our findings show that both particulate matter and gases may adversely impact BMD and that nitrogen oxides may play a critical role in bone damage and osteoporosis risk,” Dr. Prada and colleagues wrote.

Dr. Adami added: “We need more data to understand the precise magnitude of effect of air pollution on fractures, which might depend on levels of exposure but also on genetics and lifestyle.”

The study was funded by the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Adami reported receiving fees from Amgen, Eli Lilly, UCB, Fresenius Kabi, Galapagos, and Theramex.

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

Patients with moderate to severe osteoarthritis (OA) or osteonecrosis (ON) eligible for total joint arthroplasty (TJA) who have failed one or more nonoperative therapies should proceed directly to surgery, according to new guidelines from the American College of Rheumatology and the American Association of Hip and Knee Surgeons.

“One of the reasons for creating this guideline was that many patients have been subjected to delays for surgery after completing nonoperative therapy, despite persistent moderate to severe pain, loss of function, and moderate to severe radiographic OA or ON,” said coauthors Susan M. Goodman, MD, a rheumatologist at Hospital for Special Surgery in New York, and Charles Hannon, MD, an orthopedic surgeon at Washington University in St. Louis, in an email interview with this news organization. “This guideline supports surgery being performed in an expeditious fashion after the decision has been made to proceed with surgery by both the physician and patient through a shared decision-making process,” they said.

The guidelines also state that obesity by itself should not be a reason to delay TJA. “We could not find a rationale for a strict cut off for weight/body mass index (BMI). Our literature review revealed that though many adverse events were, in fact, increased in patients with morbid obesity, there is also an increase in adverse events for those who had bariatric surgery prior to their arthroplasty,” they added, noting that patients need to be made aware of the increased risk for adverse events in patients with obesity. Though the guidelines do not pose any BMI cutoffs, they state that weight loss should be “strongly encouraged.” These new recommendations are conditional, and all had a “low” to “very low” certainty of evidence; however, there was high consensus on the recommendations from the expert panel.

The guidelines also recommended:

• Delaying TJA to achieve smoking and nicotine cessation or reduction.
• Delaying TJA to improve glycemic control in patients with diabetes, although the group did not recommend any specific measure or threshold.
• Not delaying TJA in patients with a severe deformity, bone loss, or a neuropathic joint.

The new guidelines formalize what many surgeons have already been doing for the past few years, said Arjun Saxena, MD, MBA, an orthopedic surgeon in Philadelphia who was not involved with the guidelines. “A lot of total joint programs have really focused on patient optimization, including smoking cessation, glycemic control, and weight loss prior to surgery,” he said.

Most importantly, the guidelines put an emphasis on how the decision to proceed with TJA should be a shared decision between a physician and patient, he added. Some insurance companies with prior authorization policies may require a patient to try additional nonoperative therapies before approving surgery, creating barriers to care, he said. “Hopefully [these new recommendations] will help third parties understand that joint replacement is a big decision – most doctors aren’t going to recommend that unless it’s necessary or something that is going to help patients,” he said. “I understand that there is a certain need for preauthorization, but just having strict guidelines isn’t appropriate. You really need to look at the whole picture,” he added.

The full manuscript has been submitted for review and is expected to be jointly published in American College of Rheumatology and the American Association of Hip and Knee Surgeons journals later this year.

Dr. Saxena consults for the orthopedic implant company Corin.

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

Patients with moderate to severe osteoarthritis (OA) or osteonecrosis (ON) eligible for total joint arthroplasty (TJA) who have failed one or more nonoperative therapies should proceed directly to surgery, according to new guidelines from the American College of Rheumatology and the American Association of Hip and Knee Surgeons.

“One of the reasons for creating this guideline was that many patients have been subjected to delays for surgery after completing nonoperative therapy, despite persistent moderate to severe pain, loss of function, and moderate to severe radiographic OA or ON,” said coauthors Susan M. Goodman, MD, a rheumatologist at Hospital for Special Surgery in New York, and Charles Hannon, MD, an orthopedic surgeon at Washington University in St. Louis, in an email interview with this news organization. “This guideline supports surgery being performed in an expeditious fashion after the decision has been made to proceed with surgery by both the physician and patient through a shared decision-making process,” they said.

The guidelines also state that obesity by itself should not be a reason to delay TJA. “We could not find a rationale for a strict cut off for weight/body mass index (BMI). Our literature review revealed that though many adverse events were, in fact, increased in patients with morbid obesity, there is also an increase in adverse events for those who had bariatric surgery prior to their arthroplasty,” they added, noting that patients need to be made aware of the increased risk for adverse events in patients with obesity. Though the guidelines do not pose any BMI cutoffs, they state that weight loss should be “strongly encouraged.” These new recommendations are conditional, and all had a “low” to “very low” certainty of evidence; however, there was high consensus on the recommendations from the expert panel.

The guidelines also recommended:

• Delaying TJA to achieve smoking and nicotine cessation or reduction.
• Delaying TJA to improve glycemic control in patients with diabetes, although the group did not recommend any specific measure or threshold.
• Not delaying TJA in patients with a severe deformity, bone loss, or a neuropathic joint.

The new guidelines formalize what many surgeons have already been doing for the past few years, said Arjun Saxena, MD, MBA, an orthopedic surgeon in Philadelphia who was not involved with the guidelines. “A lot of total joint programs have really focused on patient optimization, including smoking cessation, glycemic control, and weight loss prior to surgery,” he said.

Most importantly, the guidelines put an emphasis on how the decision to proceed with TJA should be a shared decision between a physician and patient, he added. Some insurance companies with prior authorization policies may require a patient to try additional nonoperative therapies before approving surgery, creating barriers to care, he said. “Hopefully [these new recommendations] will help third parties understand that joint replacement is a big decision – most doctors aren’t going to recommend that unless it’s necessary or something that is going to help patients,” he said. “I understand that there is a certain need for preauthorization, but just having strict guidelines isn’t appropriate. You really need to look at the whole picture,” he added.

The full manuscript has been submitted for review and is expected to be jointly published in American College of Rheumatology and the American Association of Hip and Knee Surgeons journals later this year.

Dr. Saxena consults for the orthopedic implant company Corin.

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

Patients with moderate to severe osteoarthritis (OA) or osteonecrosis (ON) eligible for total joint arthroplasty (TJA) who have failed one or more nonoperative therapies should proceed directly to surgery, according to new guidelines from the American College of Rheumatology and the American Association of Hip and Knee Surgeons.

“One of the reasons for creating this guideline was that many patients have been subjected to delays for surgery after completing nonoperative therapy, despite persistent moderate to severe pain, loss of function, and moderate to severe radiographic OA or ON,” said coauthors Susan M. Goodman, MD, a rheumatologist at Hospital for Special Surgery in New York, and Charles Hannon, MD, an orthopedic surgeon at Washington University in St. Louis, in an email interview with this news organization. “This guideline supports surgery being performed in an expeditious fashion after the decision has been made to proceed with surgery by both the physician and patient through a shared decision-making process,” they said.

The guidelines also state that obesity by itself should not be a reason to delay TJA. “We could not find a rationale for a strict cut off for weight/body mass index (BMI). Our literature review revealed that though many adverse events were, in fact, increased in patients with morbid obesity, there is also an increase in adverse events for those who had bariatric surgery prior to their arthroplasty,” they added, noting that patients need to be made aware of the increased risk for adverse events in patients with obesity. Though the guidelines do not pose any BMI cutoffs, they state that weight loss should be “strongly encouraged.” These new recommendations are conditional, and all had a “low” to “very low” certainty of evidence; however, there was high consensus on the recommendations from the expert panel.

The guidelines also recommended:

• Delaying TJA to achieve smoking and nicotine cessation or reduction.
• Delaying TJA to improve glycemic control in patients with diabetes, although the group did not recommend any specific measure or threshold.
• Not delaying TJA in patients with a severe deformity, bone loss, or a neuropathic joint.

The new guidelines formalize what many surgeons have already been doing for the past few years, said Arjun Saxena, MD, MBA, an orthopedic surgeon in Philadelphia who was not involved with the guidelines. “A lot of total joint programs have really focused on patient optimization, including smoking cessation, glycemic control, and weight loss prior to surgery,” he said.

Most importantly, the guidelines put an emphasis on how the decision to proceed with TJA should be a shared decision between a physician and patient, he added. Some insurance companies with prior authorization policies may require a patient to try additional nonoperative therapies before approving surgery, creating barriers to care, he said. “Hopefully [these new recommendations] will help third parties understand that joint replacement is a big decision – most doctors aren’t going to recommend that unless it’s necessary or something that is going to help patients,” he said. “I understand that there is a certain need for preauthorization, but just having strict guidelines isn’t appropriate. You really need to look at the whole picture,” he added.

The full manuscript has been submitted for review and is expected to be jointly published in American College of Rheumatology and the American Association of Hip and Knee Surgeons journals later this year.

Dr. Saxena consults for the orthopedic implant company Corin.

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

NEW ORLEANS – All but one Janus kinase (JAK) inhibitor with dermatologic indications carries a boxed warning that lists multiple risks for drugs in this class, including the risk of major adverse cardiac events (MACE), even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.  

Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream. 
 

Basis of boxed warnings

In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m².

After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.

In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.

Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
 

Evidence of difference in dermatology

There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.

For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.

When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.

Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.

“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.

Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.  

Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”

“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
 

Risk-benefit considerations in dermatology

This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.

Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.

“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”

George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.

“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.

“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”

Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.

Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.

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

NEW ORLEANS – All but one Janus kinase (JAK) inhibitor with dermatologic indications carries a boxed warning that lists multiple risks for drugs in this class, including the risk of major adverse cardiac events (MACE), even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.  

Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream. 
 

Basis of boxed warnings

In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m².

After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.

In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.

Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
 

Evidence of difference in dermatology

There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.

For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.

When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.

Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.

“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.

Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.  

Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”

“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
 

Risk-benefit considerations in dermatology

This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.

Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.

“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”

George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.

“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.

“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”

Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.

Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.

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

NEW ORLEANS – All but one Janus kinase (JAK) inhibitor with dermatologic indications carries a boxed warning that lists multiple risks for drugs in this class, including the risk of major adverse cardiac events (MACE), even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.  

Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream. 
 

Basis of boxed warnings

In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m².

After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.

In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.

Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
 

Evidence of difference in dermatology

There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.

For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.

When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.

Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.

“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.

Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.  

Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”

“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
 

Risk-benefit considerations in dermatology

This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.

Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.

“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”

George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.

“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.

“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”

Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.

Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.

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

When the Food and Drug Administration approved avacopan (Tavneos) as an adjunctive treatment for severe, active antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis (AAV) in October 2021, the oral complement C5a receptor inhibitor was hailed by its developer, ChemoCentryx, as a “new hope” for patients with the disease.

But avacopan’s novelty as a new drug for the rare diseases granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), coupled with its approval as an adjunctive to standard therapy, including glucocorticoids, rather than strictly as a glucocorticoid-sparing agent as it was tested, has so far led to little reported real-world experience with the drug.

M. Alexander Otto

In the phase 3 ADVOCATE trial, the pivotal trial that served as the basis for avacopan’s approval, 331 patients with active newly diagnosed or relapsing GPA or MPA received either avacopan or an oral prednisone taper over 20 weeks on a background of cyclophosphamide followed by azathioprine or rituximab. The results of the trial showed avacopan was noninferior to the group that received prednisone taper for remission at 26 weeks and superior to prednisone taper for sustained remission at 52 weeks, but the FDA was concerned that its complex design made it difficult to define the clinically meaningful benefit of avacopan and its role in the management of AAV.

The FDA noted that, in the avacopan arm of the trial, 86% of patients received glucocorticoids outside of the study protocol. Despite this, avacopan reduced the cumulative glucocorticoid dose over the trial’s 52 weeks by nearly two-thirds, compared with the prednisone group (1,349 mg vs. 3,655 mg).

The data also indicate a higher sustained remission rate at 52 weeks in patients who received induction with rituximab, compared with cyclophosphamide. But trial did not include a maintenance therapy dose of rituximab and is thereby not a good comparison against the standard of care, the FDA said. (ADVOCATE began enrolling patients prior to the FDA's 2018 approval of an expanded indication for patients with GPA or MPA who have achieved disease control after induction treatment.)

At the FDA’s Arthritis Advisory Committee meeting in May 2021, committee members were split on whether to recommend avacopan for approval. The committee voted 9-9 on whether the ADVOCATE trial showed efficacy supporting approval of avacopan, 10-8 in favor of whether the drug’s safety profile supported approval, and 10-8 in favor of the overall benefit-risk profile of avacopan for approval. But rather than give an indication to avacopan to reduce the use of glucocorticoids in adults with GPA or MPA, the agency approved avacopan as an adjunctive treatment for severe, active disease, noting in particular that avacopan “does not eliminate glucocorticoid use.”

The European Union’s marketing authorization for avacopan states its indication for use in combination with a rituximab or cyclophosphamide regimen for the treatment of adult patients with severe, active GPA or MPA and does not mention a role for reducing glucocorticoids. Avacopan will appear in forthcoming guidelines on management of AAV released by the European Alliance of Associations for Rheumatology.

In North America, the Canadian Vasculitis Research Network recently released an addendum to their guidelines on AAV specifically for avacopan, which includes recommendations to consider adding oral avacopan (30 mg twice daily) for induction of remission in patients with new or relapsing GPA or MPA who are also receiving cyclophosphamide or rituximab. The guidelines also recommend clinicians consider a glucocorticoid tapering schedule that aims for discontinuation at 4 weeks, and continuing avacopan for at least 1 year after induction therapy. The American College of Rheumatology guideline for AAV management, updated in 2021, acknowledges avacopan but did not consider its inclusion prior to FDA approval.

There have been few real-world studies of how patients with AAV are responding to avacopan, but recent studies from researchers in the Netherlands and in France have evaluated prednisone tapering and clinical outcomes.

Anisha B. Dua, MD, an associate professor of rheumatology at Northwestern University, Chicago, said those real-world studies “seemed to re-enforce the findings from the ADVOCATE study demonstrating the efficacy of avacopan in severe disease with steroid-sparing effects.”

However, Carol Langford, MD, MHS, director of the Center for Vasculitis Care and Research at the Cleveland Clinic, emphasized caution is needed when drawing conclusions about avacopan use outside formal studies.

“We are all interested in what other settings this might be used. I think those are things that really require formal investigation to really try and understand better as far as through a study process,” she said.
 

Prescribing experience with avacopan

A spokesperson from Amgen, which recently acquired ChemoCentryx, said in an interview that over 800 physicians in the United States have prescribed avacopan to patients with new or relapsing ANCA-associated vasculitis as induction or maintenance treatment, and physicians have reported outcomes consistent with the ADVOCATE trial.

Many rheumatologists are likely familiar with avacopan but are not used to prescribing it, said Lindsay S. Lally, MD, a rheumatologist with Hospital for Special Surgery in New York.

“Rituximab was approved for GPA and MPA a decade ago at this point. It was a drug that we as rheumatologists were used to using. We used it for other indications. Avacopan is a totally new drug, a new mechanism of action, so there’s not a lot of extractable data that we have in terms of comfort with the drug, and so I think that’s one of the biggest hurdles,” she said.

Mehrnaz Hojjati, MD, a rheumatologist with Loma Linda (Calif.) University Health, said that, when the FDA approved avacopan, it was an “exciting time” in her practice. “I have used avacopan now in a handful of my patients with severe ANCA-associated vasculitis, and the results are similar to what [was] reported in the ADVOCATE trial.”

Amgen offers help for clinicians in obtaining avacopan for patients, financial assistance for patients, and support in navigating insurance, which several rheumatologists noted was important for patients. Dr. Langford said the process of working with the manufacturer to get avacopan while insurance information is being processed has been “fairly smooth.”

“Certainly, the ability to get a very rapid 30-day supply with the goal of trying to initiate this as early as possible in the disease process has been helpful,” she said.

In Dr. Dua’s experience, while there were “some glitches or difficulty for providers early on” in how to access and prescribe avacopan, since then “it has been much easier to obtain the medication with the first month being provided to patients free while the authorization process is managed.”

Prescribing avacopan from inpatient pharmacies has been more challenging, she said. “The inpatient side is trickier because each hospital system has their own pharmacy system and regulations that have to be navigated. For outpatients, all the provider needs to do is fill out the start form available on their website, have the patients sign it, and then have it sent in.”
 

Concerns about affordability, insurance approval

Another consideration is cost, with avacopan having an estimated price of $150,000-$200,000 per patient per year.

Dr. Hojjati noted that, while it is easy to prescribe, avacopan is hard to get approved through insurance. “We face the same challenge every time a new medication comes to the market on how to convince the payers to pay for it given higher prices,” she said.

Rheumatologist Michael Putman, MD, MSCI, assistant professor of medicine at the Medical College of Wisconsin, Milwaukee, also acknowledged some difficulties in prescribing the medication. “The insurance companies have no interest in spending $150,000 on a drug that they know nothing about, and patients are a little hesitant to take it because it’s just so new,” he said.

While Dr. Lally said avacopan has not been difficult to get for patients with commercial insurance, reimbursement through Medicare has been problematic. “In many of the Medicare patients it has not really been a feasible option for them to be on the drug for the year of therapy.”
 

Patient response

Dr. Dua said almost all her patients with new or relapsing AAV who require induction are being prescribed avacopan, and that the medication is well tolerated. “The remission and ability to wean prednisone has really paralleled the findings from the clinical trial.”

In her practice, Dr. Hojjati starts patients on avacopan immediately after discharge from the hospital after a major vasculitis flare requiring high-dose glucocorticoids. “Avacopan does not eliminate/replace GC [glucocorticoid] use but has a notable GC-sparing effect and assists in rapid tapering of the GC while treating our severe ANCA-associated vasculitis patients,” she said.

Dr. Lally said her patients are tolerating avacopan well and hasn’t seen any of the safety signals seen in the trial, including liver function abnormalities. She has treated about 20-25 patients with avacopan.

Dr. Putman noted that he has treated about five patients with avacopan but hasn’t seen dramatic efficacy or side effects in his practice, compared with standard therapy.

Unanswered questions about avacopan

A key unanswered question with avacopan is the timeline for tapering glucocorticoids once patients start treatment. “I would like to see much more data on how prednisone is being tapered in clinical practice as well as outcomes in patients who are treated with the standard of care second dose of rituximab at 6 months,” Dr. Dua said.

Dr. Lally noted she has tried to expedite the steroid taper in her patients. “That’s really where I feel this drug is going to have most relevance, is getting it started early in active disease and getting patients off of the reliance on high doses of oral steroids. I have been able to see that in practice, and I do think ultimately that’s going to lead to better outcomes and quality of life for these patients.”

Of the rheumatologists Dr. Lally has spoken to about avacopan, there is “some confusion about what type of patients are appropriate, [and] how sick or not sick the patient needs to be.”

Dr. Putman noted he is unsure which of his patients should be receiving avacopan. “I don’t totally have a sense for where avacopan stands and how often we should be using it” outside of patients with severe disease. He added that the drug is still trying to find a niche because most patients with AAV who take rituximab and steroids get better without additional treatments.

“I think we do a pretty good job treating these diseases even in the preavacopan era. But it’s really a matter of how to really optimize these outcomes, reduce damage, reduce steroid-related and treatment-related toxicity for our patients,” Dr. Lally said.

Dr. Dua reported being a consultant and serving on advisory boards for ChemoCentryx; she was also a site principal investigator for the ADVOCATE trial. Dr. Hojjati reported being on the speaker’s bureau for Amgen. Dr. Langford reported being an investigator in the ADVOCATE trial, and her institution received funding to conduct the trial. Dr. Lally reported being a consultant for Amgen on avacopan. Dr. Putman reported no relevant financial disclosures.

*This story was updated 3/15/2023.

When the Food and Drug Administration approved avacopan (Tavneos) as an adjunctive treatment for severe, active antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis (AAV) in October 2021, the oral complement C5a receptor inhibitor was hailed by its developer, ChemoCentryx, as a “new hope” for patients with the disease.

But avacopan’s novelty as a new drug for the rare diseases granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), coupled with its approval as an adjunctive to standard therapy, including glucocorticoids, rather than strictly as a glucocorticoid-sparing agent as it was tested, has so far led to little reported real-world experience with the drug.

M. Alexander Otto

In the phase 3 ADVOCATE trial, the pivotal trial that served as the basis for avacopan’s approval, 331 patients with active newly diagnosed or relapsing GPA or MPA received either avacopan or an oral prednisone taper over 20 weeks on a background of cyclophosphamide followed by azathioprine or rituximab. The results of the trial showed avacopan was noninferior to the group that received prednisone taper for remission at 26 weeks and superior to prednisone taper for sustained remission at 52 weeks, but the FDA was concerned that its complex design made it difficult to define the clinically meaningful benefit of avacopan and its role in the management of AAV.

The FDA noted that, in the avacopan arm of the trial, 86% of patients received glucocorticoids outside of the study protocol. Despite this, avacopan reduced the cumulative glucocorticoid dose over the trial’s 52 weeks by nearly two-thirds, compared with the prednisone group (1,349 mg vs. 3,655 mg).

The data also indicate a higher sustained remission rate at 52 weeks in patients who received induction with rituximab, compared with cyclophosphamide. But trial did not include a maintenance therapy dose of rituximab and is thereby not a good comparison against the standard of care, the FDA said. (ADVOCATE began enrolling patients prior to the FDA's 2018 approval of an expanded indication for patients with GPA or MPA who have achieved disease control after induction treatment.)

At the FDA’s Arthritis Advisory Committee meeting in May 2021, committee members were split on whether to recommend avacopan for approval. The committee voted 9-9 on whether the ADVOCATE trial showed efficacy supporting approval of avacopan, 10-8 in favor of whether the drug’s safety profile supported approval, and 10-8 in favor of the overall benefit-risk profile of avacopan for approval. But rather than give an indication to avacopan to reduce the use of glucocorticoids in adults with GPA or MPA, the agency approved avacopan as an adjunctive treatment for severe, active disease, noting in particular that avacopan “does not eliminate glucocorticoid use.”

The European Union’s marketing authorization for avacopan states its indication for use in combination with a rituximab or cyclophosphamide regimen for the treatment of adult patients with severe, active GPA or MPA and does not mention a role for reducing glucocorticoids. Avacopan will appear in forthcoming guidelines on management of AAV released by the European Alliance of Associations for Rheumatology.

In North America, the Canadian Vasculitis Research Network recently released an addendum to their guidelines on AAV specifically for avacopan, which includes recommendations to consider adding oral avacopan (30 mg twice daily) for induction of remission in patients with new or relapsing GPA or MPA who are also receiving cyclophosphamide or rituximab. The guidelines also recommend clinicians consider a glucocorticoid tapering schedule that aims for discontinuation at 4 weeks, and continuing avacopan for at least 1 year after induction therapy. The American College of Rheumatology guideline for AAV management, updated in 2021, acknowledges avacopan but did not consider its inclusion prior to FDA approval.

There have been few real-world studies of how patients with AAV are responding to avacopan, but recent studies from researchers in the Netherlands and in France have evaluated prednisone tapering and clinical outcomes.

Anisha B. Dua, MD, an associate professor of rheumatology at Northwestern University, Chicago, said those real-world studies “seemed to re-enforce the findings from the ADVOCATE study demonstrating the efficacy of avacopan in severe disease with steroid-sparing effects.”

However, Carol Langford, MD, MHS, director of the Center for Vasculitis Care and Research at the Cleveland Clinic, emphasized caution is needed when drawing conclusions about avacopan use outside formal studies.

“We are all interested in what other settings this might be used. I think those are things that really require formal investigation to really try and understand better as far as through a study process,” she said.
 

Prescribing experience with avacopan

A spokesperson from Amgen, which recently acquired ChemoCentryx, said in an interview that over 800 physicians in the United States have prescribed avacopan to patients with new or relapsing ANCA-associated vasculitis as induction or maintenance treatment, and physicians have reported outcomes consistent with the ADVOCATE trial.

Many rheumatologists are likely familiar with avacopan but are not used to prescribing it, said Lindsay S. Lally, MD, a rheumatologist with Hospital for Special Surgery in New York.

“Rituximab was approved for GPA and MPA a decade ago at this point. It was a drug that we as rheumatologists were used to using. We used it for other indications. Avacopan is a totally new drug, a new mechanism of action, so there’s not a lot of extractable data that we have in terms of comfort with the drug, and so I think that’s one of the biggest hurdles,” she said.

Mehrnaz Hojjati, MD, a rheumatologist with Loma Linda (Calif.) University Health, said that, when the FDA approved avacopan, it was an “exciting time” in her practice. “I have used avacopan now in a handful of my patients with severe ANCA-associated vasculitis, and the results are similar to what [was] reported in the ADVOCATE trial.”

Amgen offers help for clinicians in obtaining avacopan for patients, financial assistance for patients, and support in navigating insurance, which several rheumatologists noted was important for patients. Dr. Langford said the process of working with the manufacturer to get avacopan while insurance information is being processed has been “fairly smooth.”

“Certainly, the ability to get a very rapid 30-day supply with the goal of trying to initiate this as early as possible in the disease process has been helpful,” she said.

In Dr. Dua’s experience, while there were “some glitches or difficulty for providers early on” in how to access and prescribe avacopan, since then “it has been much easier to obtain the medication with the first month being provided to patients free while the authorization process is managed.”

Prescribing avacopan from inpatient pharmacies has been more challenging, she said. “The inpatient side is trickier because each hospital system has their own pharmacy system and regulations that have to be navigated. For outpatients, all the provider needs to do is fill out the start form available on their website, have the patients sign it, and then have it sent in.”
 

Concerns about affordability, insurance approval

Another consideration is cost, with avacopan having an estimated price of $150,000-$200,000 per patient per year.

Dr. Hojjati noted that, while it is easy to prescribe, avacopan is hard to get approved through insurance. “We face the same challenge every time a new medication comes to the market on how to convince the payers to pay for it given higher prices,” she said.

Rheumatologist Michael Putman, MD, MSCI, assistant professor of medicine at the Medical College of Wisconsin, Milwaukee, also acknowledged some difficulties in prescribing the medication. “The insurance companies have no interest in spending $150,000 on a drug that they know nothing about, and patients are a little hesitant to take it because it’s just so new,” he said.

While Dr. Lally said avacopan has not been difficult to get for patients with commercial insurance, reimbursement through Medicare has been problematic. “In many of the Medicare patients it has not really been a feasible option for them to be on the drug for the year of therapy.”
 

Patient response

Dr. Dua said almost all her patients with new or relapsing AAV who require induction are being prescribed avacopan, and that the medication is well tolerated. “The remission and ability to wean prednisone has really paralleled the findings from the clinical trial.”

In her practice, Dr. Hojjati starts patients on avacopan immediately after discharge from the hospital after a major vasculitis flare requiring high-dose glucocorticoids. “Avacopan does not eliminate/replace GC [glucocorticoid] use but has a notable GC-sparing effect and assists in rapid tapering of the GC while treating our severe ANCA-associated vasculitis patients,” she said.

Dr. Lally said her patients are tolerating avacopan well and hasn’t seen any of the safety signals seen in the trial, including liver function abnormalities. She has treated about 20-25 patients with avacopan.

Dr. Putman noted that he has treated about five patients with avacopan but hasn’t seen dramatic efficacy or side effects in his practice, compared with standard therapy.

Unanswered questions about avacopan

A key unanswered question with avacopan is the timeline for tapering glucocorticoids once patients start treatment. “I would like to see much more data on how prednisone is being tapered in clinical practice as well as outcomes in patients who are treated with the standard of care second dose of rituximab at 6 months,” Dr. Dua said.

Dr. Lally noted she has tried to expedite the steroid taper in her patients. “That’s really where I feel this drug is going to have most relevance, is getting it started early in active disease and getting patients off of the reliance on high doses of oral steroids. I have been able to see that in practice, and I do think ultimately that’s going to lead to better outcomes and quality of life for these patients.”

Of the rheumatologists Dr. Lally has spoken to about avacopan, there is “some confusion about what type of patients are appropriate, [and] how sick or not sick the patient needs to be.”

Dr. Putman noted he is unsure which of his patients should be receiving avacopan. “I don’t totally have a sense for where avacopan stands and how often we should be using it” outside of patients with severe disease. He added that the drug is still trying to find a niche because most patients with AAV who take rituximab and steroids get better without additional treatments.

“I think we do a pretty good job treating these diseases even in the preavacopan era. But it’s really a matter of how to really optimize these outcomes, reduce damage, reduce steroid-related and treatment-related toxicity for our patients,” Dr. Lally said.

Dr. Dua reported being a consultant and serving on advisory boards for ChemoCentryx; she was also a site principal investigator for the ADVOCATE trial. Dr. Hojjati reported being on the speaker’s bureau for Amgen. Dr. Langford reported being an investigator in the ADVOCATE trial, and her institution received funding to conduct the trial. Dr. Lally reported being a consultant for Amgen on avacopan. Dr. Putman reported no relevant financial disclosures.

*This story was updated 3/15/2023.

When the Food and Drug Administration approved avacopan (Tavneos) as an adjunctive treatment for severe, active antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis (AAV) in October 2021, the oral complement C5a receptor inhibitor was hailed by its developer, ChemoCentryx, as a “new hope” for patients with the disease.

But avacopan’s novelty as a new drug for the rare diseases granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), coupled with its approval as an adjunctive to standard therapy, including glucocorticoids, rather than strictly as a glucocorticoid-sparing agent as it was tested, has so far led to little reported real-world experience with the drug.

M. Alexander Otto

In the phase 3 ADVOCATE trial, the pivotal trial that served as the basis for avacopan’s approval, 331 patients with active newly diagnosed or relapsing GPA or MPA received either avacopan or an oral prednisone taper over 20 weeks on a background of cyclophosphamide followed by azathioprine or rituximab. The results of the trial showed avacopan was noninferior to the group that received prednisone taper for remission at 26 weeks and superior to prednisone taper for sustained remission at 52 weeks, but the FDA was concerned that its complex design made it difficult to define the clinically meaningful benefit of avacopan and its role in the management of AAV.

The FDA noted that, in the avacopan arm of the trial, 86% of patients received glucocorticoids outside of the study protocol. Despite this, avacopan reduced the cumulative glucocorticoid dose over the trial’s 52 weeks by nearly two-thirds, compared with the prednisone group (1,349 mg vs. 3,655 mg).

The data also indicate a higher sustained remission rate at 52 weeks in patients who received induction with rituximab, compared with cyclophosphamide. But trial did not include a maintenance therapy dose of rituximab and is thereby not a good comparison against the standard of care, the FDA said. (ADVOCATE began enrolling patients prior to the FDA's 2018 approval of an expanded indication for patients with GPA or MPA who have achieved disease control after induction treatment.)

At the FDA’s Arthritis Advisory Committee meeting in May 2021, committee members were split on whether to recommend avacopan for approval. The committee voted 9-9 on whether the ADVOCATE trial showed efficacy supporting approval of avacopan, 10-8 in favor of whether the drug’s safety profile supported approval, and 10-8 in favor of the overall benefit-risk profile of avacopan for approval. But rather than give an indication to avacopan to reduce the use of glucocorticoids in adults with GPA or MPA, the agency approved avacopan as an adjunctive treatment for severe, active disease, noting in particular that avacopan “does not eliminate glucocorticoid use.”

The European Union’s marketing authorization for avacopan states its indication for use in combination with a rituximab or cyclophosphamide regimen for the treatment of adult patients with severe, active GPA or MPA and does not mention a role for reducing glucocorticoids. Avacopan will appear in forthcoming guidelines on management of AAV released by the European Alliance of Associations for Rheumatology.

In North America, the Canadian Vasculitis Research Network recently released an addendum to their guidelines on AAV specifically for avacopan, which includes recommendations to consider adding oral avacopan (30 mg twice daily) for induction of remission in patients with new or relapsing GPA or MPA who are also receiving cyclophosphamide or rituximab. The guidelines also recommend clinicians consider a glucocorticoid tapering schedule that aims for discontinuation at 4 weeks, and continuing avacopan for at least 1 year after induction therapy. The American College of Rheumatology guideline for AAV management, updated in 2021, acknowledges avacopan but did not consider its inclusion prior to FDA approval.

There have been few real-world studies of how patients with AAV are responding to avacopan, but recent studies from researchers in the Netherlands and in France have evaluated prednisone tapering and clinical outcomes.

Anisha B. Dua, MD, an associate professor of rheumatology at Northwestern University, Chicago, said those real-world studies “seemed to re-enforce the findings from the ADVOCATE study demonstrating the efficacy of avacopan in severe disease with steroid-sparing effects.”

However, Carol Langford, MD, MHS, director of the Center for Vasculitis Care and Research at the Cleveland Clinic, emphasized caution is needed when drawing conclusions about avacopan use outside formal studies.

“We are all interested in what other settings this might be used. I think those are things that really require formal investigation to really try and understand better as far as through a study process,” she said.
 

Prescribing experience with avacopan

A spokesperson from Amgen, which recently acquired ChemoCentryx, said in an interview that over 800 physicians in the United States have prescribed avacopan to patients with new or relapsing ANCA-associated vasculitis as induction or maintenance treatment, and physicians have reported outcomes consistent with the ADVOCATE trial.

Many rheumatologists are likely familiar with avacopan but are not used to prescribing it, said Lindsay S. Lally, MD, a rheumatologist with Hospital for Special Surgery in New York.

“Rituximab was approved for GPA and MPA a decade ago at this point. It was a drug that we as rheumatologists were used to using. We used it for other indications. Avacopan is a totally new drug, a new mechanism of action, so there’s not a lot of extractable data that we have in terms of comfort with the drug, and so I think that’s one of the biggest hurdles,” she said.

Mehrnaz Hojjati, MD, a rheumatologist with Loma Linda (Calif.) University Health, said that, when the FDA approved avacopan, it was an “exciting time” in her practice. “I have used avacopan now in a handful of my patients with severe ANCA-associated vasculitis, and the results are similar to what [was] reported in the ADVOCATE trial.”

Amgen offers help for clinicians in obtaining avacopan for patients, financial assistance for patients, and support in navigating insurance, which several rheumatologists noted was important for patients. Dr. Langford said the process of working with the manufacturer to get avacopan while insurance information is being processed has been “fairly smooth.”

“Certainly, the ability to get a very rapid 30-day supply with the goal of trying to initiate this as early as possible in the disease process has been helpful,” she said.

In Dr. Dua’s experience, while there were “some glitches or difficulty for providers early on” in how to access and prescribe avacopan, since then “it has been much easier to obtain the medication with the first month being provided to patients free while the authorization process is managed.”

Prescribing avacopan from inpatient pharmacies has been more challenging, she said. “The inpatient side is trickier because each hospital system has their own pharmacy system and regulations that have to be navigated. For outpatients, all the provider needs to do is fill out the start form available on their website, have the patients sign it, and then have it sent in.”
 

Concerns about affordability, insurance approval

Another consideration is cost, with avacopan having an estimated price of $150,000-$200,000 per patient per year.

Dr. Hojjati noted that, while it is easy to prescribe, avacopan is hard to get approved through insurance. “We face the same challenge every time a new medication comes to the market on how to convince the payers to pay for it given higher prices,” she said.

Rheumatologist Michael Putman, MD, MSCI, assistant professor of medicine at the Medical College of Wisconsin, Milwaukee, also acknowledged some difficulties in prescribing the medication. “The insurance companies have no interest in spending $150,000 on a drug that they know nothing about, and patients are a little hesitant to take it because it’s just so new,” he said.

While Dr. Lally said avacopan has not been difficult to get for patients with commercial insurance, reimbursement through Medicare has been problematic. “In many of the Medicare patients it has not really been a feasible option for them to be on the drug for the year of therapy.”
 

Patient response

Dr. Dua said almost all her patients with new or relapsing AAV who require induction are being prescribed avacopan, and that the medication is well tolerated. “The remission and ability to wean prednisone has really paralleled the findings from the clinical trial.”

In her practice, Dr. Hojjati starts patients on avacopan immediately after discharge from the hospital after a major vasculitis flare requiring high-dose glucocorticoids. “Avacopan does not eliminate/replace GC [glucocorticoid] use but has a notable GC-sparing effect and assists in rapid tapering of the GC while treating our severe ANCA-associated vasculitis patients,” she said.

Dr. Lally said her patients are tolerating avacopan well and hasn’t seen any of the safety signals seen in the trial, including liver function abnormalities. She has treated about 20-25 patients with avacopan.

Dr. Putman noted that he has treated about five patients with avacopan but hasn’t seen dramatic efficacy or side effects in his practice, compared with standard therapy.

Unanswered questions about avacopan

A key unanswered question with avacopan is the timeline for tapering glucocorticoids once patients start treatment. “I would like to see much more data on how prednisone is being tapered in clinical practice as well as outcomes in patients who are treated with the standard of care second dose of rituximab at 6 months,” Dr. Dua said.

Dr. Lally noted she has tried to expedite the steroid taper in her patients. “That’s really where I feel this drug is going to have most relevance, is getting it started early in active disease and getting patients off of the reliance on high doses of oral steroids. I have been able to see that in practice, and I do think ultimately that’s going to lead to better outcomes and quality of life for these patients.”

Of the rheumatologists Dr. Lally has spoken to about avacopan, there is “some confusion about what type of patients are appropriate, [and] how sick or not sick the patient needs to be.”

Dr. Putman noted he is unsure which of his patients should be receiving avacopan. “I don’t totally have a sense for where avacopan stands and how often we should be using it” outside of patients with severe disease. He added that the drug is still trying to find a niche because most patients with AAV who take rituximab and steroids get better without additional treatments.

“I think we do a pretty good job treating these diseases even in the preavacopan era. But it’s really a matter of how to really optimize these outcomes, reduce damage, reduce steroid-related and treatment-related toxicity for our patients,” Dr. Lally said.

Dr. Dua reported being a consultant and serving on advisory boards for ChemoCentryx; she was also a site principal investigator for the ADVOCATE trial. Dr. Hojjati reported being on the speaker’s bureau for Amgen. Dr. Langford reported being an investigator in the ADVOCATE trial, and her institution received funding to conduct the trial. Dr. Lally reported being a consultant for Amgen on avacopan. Dr. Putman reported no relevant financial disclosures.

*This story was updated 3/15/2023.