Rheumatology

Progressive resistance training (PRT) and neuromuscular exercise (NEMEX) programs result in similar improvements in hip function, pain, and hip-related quality of life (QOL) in people with osteoarthritis (OA), according to the results of a randomized controlled trial.

At the end of the 12-week exercise period, both interventions yielded changes from baseline on the 30-second chair stand test (30s-CST) that were below the threshold for a major clinical effect. 

Mean changes in the Hip Disability and Osteoarthritis Outcome Score (HOOS) pain subscale and HOOS QOL score were also similar among the participants, regardless of which exercise program they had been assigned to.

“The lack of superiority of PRT for increasing muscle strength and power is surprising given the principle of specificity (higher-intensity resistance training yields greater improvements in maximal muscle strength),” according to the Danish researchers who reported the results online today in Annals of Internal Medicine.

“However, the point estimates only showed modest and uncertain superiority of PRT for increasing muscle strength and power and no differences for any functional performance tests or self-reported physical function,” they added.
 

The Power of Exercise

Worldwide, most clinical guidelines recommend exercise as a first-line conservative treatment option in both hip and knee OA. However, there is not much evidence to help guide healthcare practitioners in deciding which type of exercises to use with their patients, Troels Kjeldsen, MSc, the principal investigator for the study, told this news organization.

“Neuromuscular exercise is a very commonly used exercise program in clinical practice, but, to our knowledge, it has never been compared to another type of exercise in hip OA,” observed Mr. Kjeldsen, who is a PhD student in the department of orthopedic surgery at Aarhus University Hospital, Aarhus, Denmark.

“Each year, many thousands of patients are referred to having neuromuscular exercise therapy with a physiotherapist,” Mr. Kjeldsen said. “So, we thought it would be worthwhile to compare it to PRT, another promising exercise type, to see if it really did perform as well as I think most people thought it did,” he added.
 

Comparing the Two Exercise Programs

PRT and NEMEX are two different types of exercise programs. PRT involves using resistance-training machines, and the focus is to maximize the exercise intensity by using as high an exercise load or weight as possible. By contrast, NEMEX consists of exercises that are low to moderate in intensity and emphasizes alignment, control, and stability of the movements.

To compare the two exercise strategies, Mr. Kjeldsen and fellow investigators recruited 160 participants at five hospitals and 10 physiotherapy clinics across three of five healthcare regions in Denmark.

For inclusion in the trial, the participants had to have a clinical diagnosis of hip OA, be older than 45 years, and experience pain during activity in one or both hips that was rated as 3 or higher on a 10-point numerical rating scale. Participants also had to have no or less than 30 minutes of hip joint stiffness in the morning as well as no surgery involving the lower extremities in the previous 6 months. 

Participants were then randomized to undertake the PRT (n = 82) or NEMEX (n = 78) program, delivered as two physiotherapist-led group sessions every week for 12 weeks. Exercise sessions were held at least 72 hours apart and consisted of a 10-minute warm-up on an exercise bike and then 50 minutes of PRT or NEMEX. PRT consisted of five generic resistance-based exercises targeting hip and knee joint muscles and NEMEX consisted of 10 exercises that increased in difficulty by varying the number, direction, speed, and surface of the movements performed.
 

Dead Heat Between PRT and NEMEX

The primary endpoint was the 30s-CST, which counted the number of times participants could stand from a seated position in 30 seconds. Participants in the PRT and NEMEX groups were able to do this maneuver a respective 11.3 and 11.6 times at baseline and 12.8 and 13.1 times after completion of the exercise programs. 

Other functional performance tests included a 40-m fast-paced walk, a nine-step timed stair climb, leg extensor power in the affected and unaffected limb, and a unilateral single repetition leg press. None of these showed a statistically significant benefit of PRT over NEMEX, or vice versa.

HOOS pain scores at baseline and 12 weeks for PRT were a respective 57.5 and 66.1, representing an overall 8.6-point increase, and for NEMEX they were 58.9 and 68.2, giving a 9.3-point increase, meaning there was only a -0.7 mean change when comparing the two groups.

Corresponding baseline and 12-week HOOS QOL scores for PRT were 43.7 and 51.7; for NEMEX, they were 47.1 and 52.8 thus giving 8.0- and 5.7-point increases and a 2.3 difference in change between the groups. Again, this wasn’t quite enough to show a clinically meaningful effect.
 

Future Steps

“The effect of exercise seems to be at its highest at 3-4 months when you implement exercise, so we compared the effects of the exercises at the time when they are probably going to be at their highest,” Mr. Kjeldsen explained. He said the research team also plans to look at what happens after 1 year of follow-up.

“The key take home message is that patients can be encouraged to pick the type of exercise that they find the most enjoyable, or the type that is available to them,” Mr. Kjeldsen suggested. 

Stephanie Chang, MD, MPH, who is the Deputy Editor of Annals of Internal Medicine and practices in Rockville, Maryland, commented on the paper to this news organization. “In this small study, we learned that exercises to strengthen lower extremity muscles did not improve pain or function any more than exercises for core stability and balance,” she said.

Dr. Chang pointed out that there was variance in the levels of activity that people already undertook at baseline: 40% of the PRT group and 41% of the NEMEX group already did 150 minutes or more of moderate intensity physical activity. 

“It’s possible that benefit or differences between interventions would be greater in people with different levels of baseline activity or even in those with different osteoarthritis severity,” she said. 

“In the meantime,” Dr. Chang added, “with the findings from this study, I would feel comfortable advising my patients with hip osteoarthritis to engage in whichever type of exercise they prefer — whether that exercise focuses on core strengthening and balance or on specific lower extremity muscle strengthening.”

The trial was funded by the Independent Research Fund Denmark, the Physiotherapy Practice Foundation, the Health Foundation, Aarhus University, Region Zealand, the Association of Danish Physiotherapists, Andelsfonden, and Hede Nielsens Family Foundation. Mr. Kjeldsen and Dr. Chang report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Progressive resistance training (PRT) and neuromuscular exercise (NEMEX) programs result in similar improvements in hip function, pain, and hip-related quality of life (QOL) in people with osteoarthritis (OA), according to the results of a randomized controlled trial.

At the end of the 12-week exercise period, both interventions yielded changes from baseline on the 30-second chair stand test (30s-CST) that were below the threshold for a major clinical effect. 

Mean changes in the Hip Disability and Osteoarthritis Outcome Score (HOOS) pain subscale and HOOS QOL score were also similar among the participants, regardless of which exercise program they had been assigned to.

“The lack of superiority of PRT for increasing muscle strength and power is surprising given the principle of specificity (higher-intensity resistance training yields greater improvements in maximal muscle strength),” according to the Danish researchers who reported the results online today in Annals of Internal Medicine.

“However, the point estimates only showed modest and uncertain superiority of PRT for increasing muscle strength and power and no differences for any functional performance tests or self-reported physical function,” they added.
 

The Power of Exercise

Worldwide, most clinical guidelines recommend exercise as a first-line conservative treatment option in both hip and knee OA. However, there is not much evidence to help guide healthcare practitioners in deciding which type of exercises to use with their patients, Troels Kjeldsen, MSc, the principal investigator for the study, told this news organization.

“Neuromuscular exercise is a very commonly used exercise program in clinical practice, but, to our knowledge, it has never been compared to another type of exercise in hip OA,” observed Mr. Kjeldsen, who is a PhD student in the department of orthopedic surgery at Aarhus University Hospital, Aarhus, Denmark.

“Each year, many thousands of patients are referred to having neuromuscular exercise therapy with a physiotherapist,” Mr. Kjeldsen said. “So, we thought it would be worthwhile to compare it to PRT, another promising exercise type, to see if it really did perform as well as I think most people thought it did,” he added.
 

Comparing the Two Exercise Programs

PRT and NEMEX are two different types of exercise programs. PRT involves using resistance-training machines, and the focus is to maximize the exercise intensity by using as high an exercise load or weight as possible. By contrast, NEMEX consists of exercises that are low to moderate in intensity and emphasizes alignment, control, and stability of the movements.

To compare the two exercise strategies, Mr. Kjeldsen and fellow investigators recruited 160 participants at five hospitals and 10 physiotherapy clinics across three of five healthcare regions in Denmark.

For inclusion in the trial, the participants had to have a clinical diagnosis of hip OA, be older than 45 years, and experience pain during activity in one or both hips that was rated as 3 or higher on a 10-point numerical rating scale. Participants also had to have no or less than 30 minutes of hip joint stiffness in the morning as well as no surgery involving the lower extremities in the previous 6 months. 

Participants were then randomized to undertake the PRT (n = 82) or NEMEX (n = 78) program, delivered as two physiotherapist-led group sessions every week for 12 weeks. Exercise sessions were held at least 72 hours apart and consisted of a 10-minute warm-up on an exercise bike and then 50 minutes of PRT or NEMEX. PRT consisted of five generic resistance-based exercises targeting hip and knee joint muscles and NEMEX consisted of 10 exercises that increased in difficulty by varying the number, direction, speed, and surface of the movements performed.
 

Dead Heat Between PRT and NEMEX

The primary endpoint was the 30s-CST, which counted the number of times participants could stand from a seated position in 30 seconds. Participants in the PRT and NEMEX groups were able to do this maneuver a respective 11.3 and 11.6 times at baseline and 12.8 and 13.1 times after completion of the exercise programs. 

Other functional performance tests included a 40-m fast-paced walk, a nine-step timed stair climb, leg extensor power in the affected and unaffected limb, and a unilateral single repetition leg press. None of these showed a statistically significant benefit of PRT over NEMEX, or vice versa.

HOOS pain scores at baseline and 12 weeks for PRT were a respective 57.5 and 66.1, representing an overall 8.6-point increase, and for NEMEX they were 58.9 and 68.2, giving a 9.3-point increase, meaning there was only a -0.7 mean change when comparing the two groups.

Corresponding baseline and 12-week HOOS QOL scores for PRT were 43.7 and 51.7; for NEMEX, they were 47.1 and 52.8 thus giving 8.0- and 5.7-point increases and a 2.3 difference in change between the groups. Again, this wasn’t quite enough to show a clinically meaningful effect.
 

Future Steps

“The effect of exercise seems to be at its highest at 3-4 months when you implement exercise, so we compared the effects of the exercises at the time when they are probably going to be at their highest,” Mr. Kjeldsen explained. He said the research team also plans to look at what happens after 1 year of follow-up.

“The key take home message is that patients can be encouraged to pick the type of exercise that they find the most enjoyable, or the type that is available to them,” Mr. Kjeldsen suggested. 

Stephanie Chang, MD, MPH, who is the Deputy Editor of Annals of Internal Medicine and practices in Rockville, Maryland, commented on the paper to this news organization. “In this small study, we learned that exercises to strengthen lower extremity muscles did not improve pain or function any more than exercises for core stability and balance,” she said.

Dr. Chang pointed out that there was variance in the levels of activity that people already undertook at baseline: 40% of the PRT group and 41% of the NEMEX group already did 150 minutes or more of moderate intensity physical activity. 

“It’s possible that benefit or differences between interventions would be greater in people with different levels of baseline activity or even in those with different osteoarthritis severity,” she said. 

“In the meantime,” Dr. Chang added, “with the findings from this study, I would feel comfortable advising my patients with hip osteoarthritis to engage in whichever type of exercise they prefer — whether that exercise focuses on core strengthening and balance or on specific lower extremity muscle strengthening.”

The trial was funded by the Independent Research Fund Denmark, the Physiotherapy Practice Foundation, the Health Foundation, Aarhus University, Region Zealand, the Association of Danish Physiotherapists, Andelsfonden, and Hede Nielsens Family Foundation. Mr. Kjeldsen and Dr. Chang report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Progressive resistance training (PRT) and neuromuscular exercise (NEMEX) programs result in similar improvements in hip function, pain, and hip-related quality of life (QOL) in people with osteoarthritis (OA), according to the results of a randomized controlled trial.

At the end of the 12-week exercise period, both interventions yielded changes from baseline on the 30-second chair stand test (30s-CST) that were below the threshold for a major clinical effect. 

Mean changes in the Hip Disability and Osteoarthritis Outcome Score (HOOS) pain subscale and HOOS QOL score were also similar among the participants, regardless of which exercise program they had been assigned to.

“The lack of superiority of PRT for increasing muscle strength and power is surprising given the principle of specificity (higher-intensity resistance training yields greater improvements in maximal muscle strength),” according to the Danish researchers who reported the results online today in Annals of Internal Medicine.

“However, the point estimates only showed modest and uncertain superiority of PRT for increasing muscle strength and power and no differences for any functional performance tests or self-reported physical function,” they added.
 

The Power of Exercise

Worldwide, most clinical guidelines recommend exercise as a first-line conservative treatment option in both hip and knee OA. However, there is not much evidence to help guide healthcare practitioners in deciding which type of exercises to use with their patients, Troels Kjeldsen, MSc, the principal investigator for the study, told this news organization.

“Neuromuscular exercise is a very commonly used exercise program in clinical practice, but, to our knowledge, it has never been compared to another type of exercise in hip OA,” observed Mr. Kjeldsen, who is a PhD student in the department of orthopedic surgery at Aarhus University Hospital, Aarhus, Denmark.

“Each year, many thousands of patients are referred to having neuromuscular exercise therapy with a physiotherapist,” Mr. Kjeldsen said. “So, we thought it would be worthwhile to compare it to PRT, another promising exercise type, to see if it really did perform as well as I think most people thought it did,” he added.
 

Comparing the Two Exercise Programs

PRT and NEMEX are two different types of exercise programs. PRT involves using resistance-training machines, and the focus is to maximize the exercise intensity by using as high an exercise load or weight as possible. By contrast, NEMEX consists of exercises that are low to moderate in intensity and emphasizes alignment, control, and stability of the movements.

To compare the two exercise strategies, Mr. Kjeldsen and fellow investigators recruited 160 participants at five hospitals and 10 physiotherapy clinics across three of five healthcare regions in Denmark.

For inclusion in the trial, the participants had to have a clinical diagnosis of hip OA, be older than 45 years, and experience pain during activity in one or both hips that was rated as 3 or higher on a 10-point numerical rating scale. Participants also had to have no or less than 30 minutes of hip joint stiffness in the morning as well as no surgery involving the lower extremities in the previous 6 months. 

Participants were then randomized to undertake the PRT (n = 82) or NEMEX (n = 78) program, delivered as two physiotherapist-led group sessions every week for 12 weeks. Exercise sessions were held at least 72 hours apart and consisted of a 10-minute warm-up on an exercise bike and then 50 minutes of PRT or NEMEX. PRT consisted of five generic resistance-based exercises targeting hip and knee joint muscles and NEMEX consisted of 10 exercises that increased in difficulty by varying the number, direction, speed, and surface of the movements performed.
 

Dead Heat Between PRT and NEMEX

The primary endpoint was the 30s-CST, which counted the number of times participants could stand from a seated position in 30 seconds. Participants in the PRT and NEMEX groups were able to do this maneuver a respective 11.3 and 11.6 times at baseline and 12.8 and 13.1 times after completion of the exercise programs. 

Other functional performance tests included a 40-m fast-paced walk, a nine-step timed stair climb, leg extensor power in the affected and unaffected limb, and a unilateral single repetition leg press. None of these showed a statistically significant benefit of PRT over NEMEX, or vice versa.

HOOS pain scores at baseline and 12 weeks for PRT were a respective 57.5 and 66.1, representing an overall 8.6-point increase, and for NEMEX they were 58.9 and 68.2, giving a 9.3-point increase, meaning there was only a -0.7 mean change when comparing the two groups.

Corresponding baseline and 12-week HOOS QOL scores for PRT were 43.7 and 51.7; for NEMEX, they were 47.1 and 52.8 thus giving 8.0- and 5.7-point increases and a 2.3 difference in change between the groups. Again, this wasn’t quite enough to show a clinically meaningful effect.
 

Future Steps

“The effect of exercise seems to be at its highest at 3-4 months when you implement exercise, so we compared the effects of the exercises at the time when they are probably going to be at their highest,” Mr. Kjeldsen explained. He said the research team also plans to look at what happens after 1 year of follow-up.

“The key take home message is that patients can be encouraged to pick the type of exercise that they find the most enjoyable, or the type that is available to them,” Mr. Kjeldsen suggested. 

Stephanie Chang, MD, MPH, who is the Deputy Editor of Annals of Internal Medicine and practices in Rockville, Maryland, commented on the paper to this news organization. “In this small study, we learned that exercises to strengthen lower extremity muscles did not improve pain or function any more than exercises for core stability and balance,” she said.

Dr. Chang pointed out that there was variance in the levels of activity that people already undertook at baseline: 40% of the PRT group and 41% of the NEMEX group already did 150 minutes or more of moderate intensity physical activity. 

“It’s possible that benefit or differences between interventions would be greater in people with different levels of baseline activity or even in those with different osteoarthritis severity,” she said. 

“In the meantime,” Dr. Chang added, “with the findings from this study, I would feel comfortable advising my patients with hip osteoarthritis to engage in whichever type of exercise they prefer — whether that exercise focuses on core strengthening and balance or on specific lower extremity muscle strengthening.”

The trial was funded by the Independent Research Fund Denmark, the Physiotherapy Practice Foundation, the Health Foundation, Aarhus University, Region Zealand, the Association of Danish Physiotherapists, Andelsfonden, and Hede Nielsens Family Foundation. Mr. Kjeldsen and Dr. Chang report no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) have a high risk for serious and fatal infections, with age, inflammation, and corticosteroid therapy further increasing this risk.

METHODOLOGY:

• Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.
• This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.
• Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).
• Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.

TAKEAWAY:

• During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.
• Respiratory infections were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.
• Most infections were caused by SARS-CoV-2 (33.5%), Streptococcus pneumoniae (11.9%), Escherichia coli (11.9%), and Pseudomonas aeruginosa (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for P aeruginosa (12.9%), and 9.6% for pneumococci (9.6%).
• Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.

IN PRACTICE:

“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.

SOURCE:

This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and published online March 27 in Frontiers in Immunology.

LIMITATIONS:

The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.

DISCLOSURE:

This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) have a high risk for serious and fatal infections, with age, inflammation, and corticosteroid therapy further increasing this risk.

METHODOLOGY:

• Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.
• This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.
• Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).
• Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.

TAKEAWAY:

• During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.
• Respiratory infections were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.
• Most infections were caused by SARS-CoV-2 (33.5%), Streptococcus pneumoniae (11.9%), Escherichia coli (11.9%), and Pseudomonas aeruginosa (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for P aeruginosa (12.9%), and 9.6% for pneumococci (9.6%).
• Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.

IN PRACTICE:

“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.

SOURCE:

This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and published online March 27 in Frontiers in Immunology.

LIMITATIONS:

The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.

DISCLOSURE:

This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) have a high risk for serious and fatal infections, with age, inflammation, and corticosteroid therapy further increasing this risk.

METHODOLOGY:

• Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.
• This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.
• Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).
• Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.

TAKEAWAY:

• During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.
• Respiratory infections were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.
• Most infections were caused by SARS-CoV-2 (33.5%), Streptococcus pneumoniae (11.9%), Escherichia coli (11.9%), and Pseudomonas aeruginosa (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for P aeruginosa (12.9%), and 9.6% for pneumococci (9.6%).
• Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.

IN PRACTICE:

“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.

SOURCE:

This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and published online March 27 in Frontiers in Immunology.

LIMITATIONS:

The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.

DISCLOSURE:

This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.
 

A version of this article appeared on Medscape.com.

Congress provided $10 million to fund arthritis research in the recently passed federal fiscal year 2024 budget.

The new arthritis program is part of the Department of Defense’s (DOD’s) Congressionally Directed Medical Research Programs (CDMRP), which provides dedicated funding to study certain diseases and health conditions.

This is the first stand-alone research program for arthritis of the CDMRP, though the organization had previously funded arthritis-related research through their other programs, including chronic pain management, joint warfighter medical, peer-reviewed orthopedic, peer-reviewed medical, and tick-borne disease programs.

Lucidology/Thinkstock

It is not yet known what specific aspects of arthritis this funding will go toward. The standard process for new programs involves speaking with researchers, clinicians, and individuals with these targeted health conditions to better understand research gaps and narrow focus, Akua Roach, PhD, the program manager for this new CDMRP arthritis research program, told this news organization.

“We’re not going to be able to solve every question,” she said, though the allocated $10 million is “a great number to do a lot of great work.”

While the CDMRP is under the DOD, research funding can go to studying patient populations outside of military personnel or veterans, she added.

“I think that is perhaps a common misconception that if you are getting funding from the DOD, that you have to have a DOD population, and that is not true,” she said.

Another misconception is that CDMRP funding only goes to military treatment facilities. In fact, on average, 92% of CDMRP funding goes to academia, industry, and other nonmilitary recipients, noted CDMRP Director Colonel Sarah Goldman.

“Anyone around the world can apply for funding,” she told this news organization. “We want to fund the best research.”

Because the funding is provided under the defense bill, there will be discussions around the military relevance of research, she added, which not only includes service members but also their families.

CDMRP anticipates that funding opportunities through this new arthritis research program will be available by July or August 2024.
 

A version of this article appeared on Medscape.com.

Congress provided $10 million to fund arthritis research in the recently passed federal fiscal year 2024 budget.

The new arthritis program is part of the Department of Defense’s (DOD’s) Congressionally Directed Medical Research Programs (CDMRP), which provides dedicated funding to study certain diseases and health conditions.

This is the first stand-alone research program for arthritis of the CDMRP, though the organization had previously funded arthritis-related research through their other programs, including chronic pain management, joint warfighter medical, peer-reviewed orthopedic, peer-reviewed medical, and tick-borne disease programs.

Lucidology/Thinkstock

It is not yet known what specific aspects of arthritis this funding will go toward. The standard process for new programs involves speaking with researchers, clinicians, and individuals with these targeted health conditions to better understand research gaps and narrow focus, Akua Roach, PhD, the program manager for this new CDMRP arthritis research program, told this news organization.

“We’re not going to be able to solve every question,” she said, though the allocated $10 million is “a great number to do a lot of great work.”

While the CDMRP is under the DOD, research funding can go to studying patient populations outside of military personnel or veterans, she added.

“I think that is perhaps a common misconception that if you are getting funding from the DOD, that you have to have a DOD population, and that is not true,” she said.

Another misconception is that CDMRP funding only goes to military treatment facilities. In fact, on average, 92% of CDMRP funding goes to academia, industry, and other nonmilitary recipients, noted CDMRP Director Colonel Sarah Goldman.

“Anyone around the world can apply for funding,” she told this news organization. “We want to fund the best research.”

Because the funding is provided under the defense bill, there will be discussions around the military relevance of research, she added, which not only includes service members but also their families.

CDMRP anticipates that funding opportunities through this new arthritis research program will be available by July or August 2024.
 

A version of this article appeared on Medscape.com.

Congress provided $10 million to fund arthritis research in the recently passed federal fiscal year 2024 budget.

The new arthritis program is part of the Department of Defense’s (DOD’s) Congressionally Directed Medical Research Programs (CDMRP), which provides dedicated funding to study certain diseases and health conditions.

This is the first stand-alone research program for arthritis of the CDMRP, though the organization had previously funded arthritis-related research through their other programs, including chronic pain management, joint warfighter medical, peer-reviewed orthopedic, peer-reviewed medical, and tick-borne disease programs.

Lucidology/Thinkstock

It is not yet known what specific aspects of arthritis this funding will go toward. The standard process for new programs involves speaking with researchers, clinicians, and individuals with these targeted health conditions to better understand research gaps and narrow focus, Akua Roach, PhD, the program manager for this new CDMRP arthritis research program, told this news organization.

“We’re not going to be able to solve every question,” she said, though the allocated $10 million is “a great number to do a lot of great work.”

While the CDMRP is under the DOD, research funding can go to studying patient populations outside of military personnel or veterans, she added.

“I think that is perhaps a common misconception that if you are getting funding from the DOD, that you have to have a DOD population, and that is not true,” she said.

Another misconception is that CDMRP funding only goes to military treatment facilities. In fact, on average, 92% of CDMRP funding goes to academia, industry, and other nonmilitary recipients, noted CDMRP Director Colonel Sarah Goldman.

“Anyone around the world can apply for funding,” she told this news organization. “We want to fund the best research.”

Because the funding is provided under the defense bill, there will be discussions around the military relevance of research, she added, which not only includes service members but also their families.

CDMRP anticipates that funding opportunities through this new arthritis research program will be available by July or August 2024.
 

A version of this article appeared on Medscape.com.

TOPLINE:

After Staphylococcus aureus bacteremia, patients with rheumatoid arthritis (RA) face nearly double the risk for osteoarticular infections compared with those without RA, with similar mortality risks in both groups.

METHODOLOGY:

• The contraction of S aureus bacteremia is linked to poor clinical outcomes in patients with RA; however, no well-sized studies have evaluated the risk for osteoarticular infections and mortality outcomes in patients with RA following S aureus bacteremia.
• This Danish nationwide cohort study aimed to explore whether the cumulative incidence of osteoarticular infections and death would be higher in patients with RA than in those without RA after contracting S aureus bacteremia.
• The study cohort included 18,274 patients with a first episode of S aureus bacteremia between 2006 and 2018, of whom 367 had been diagnosed with RA before contracting S aureus bacteremia.
• The RA cohort had more women (62%) and a higher median age of participants (73 years) than the non-RA cohort (37% women; median age of participants, 70 years).

TAKEAWAY:

• The 90-day cumulative incidence of osteoarticular infections (septic arthritis, spondylitis, osteomyelitis, psoas muscle abscess, or prosthetic joint infection) was nearly double in patients with RA compared with in those without RA (23.1% vs 12.5%; hazard ratio [HR], 1.93; 95% CI, 1.54-2.41).
• In patients with RA, the risk for osteoarticular infections increased with tumor necrosis factor inhibitor use (HR, 2.27; 95% CI, 1.29-3.98) and orthopedic implants (HR, 1.75; 95% CI, 1.08-2.85).
• Moreover, 90-day all-cause mortality was comparable in the RA (35.4%) and non-RA cohorts (33.9%).

IN PRACTICE:

“Our findings stress the need for vigilance in patients with RA who present with S aureus bacteremia to ensure timely identification and treatment of osteoarticular infections, especially in current TNFi [tumor necrosis factor inhibitor] users and patients with orthopedic implants,” the authors wrote.

SOURCE:

This study, led by Sabine S. Dieperink, MD, of the Centre of Head and Orthopaedics, Copenhagen University Rigshospitalet Glostrup, Denmark, was published online March 9 in Rheumatology (Oxford).

LIMITATIONS:

There might have been chances of misclassification of metastatic S aureus infections owing to the lack of specificity in diagnoses or procedure codes. This study relied on administrative data to record osteoarticular infections, which might have led investigators to underestimate the true cumulative incidence of osteoarticular infections. Also, some patients might have passed away before being diagnosed with osteoarticular infection owing to the high mortality.

DISCLOSURES:

This work was supported by grants from The Danish Rheumatism Association and Beckett Fonden. Some of the authors, including the lead author, declared receiving grants from various funding agencies and other sources, including pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

After Staphylococcus aureus bacteremia, patients with rheumatoid arthritis (RA) face nearly double the risk for osteoarticular infections compared with those without RA, with similar mortality risks in both groups.

METHODOLOGY:

• The contraction of S aureus bacteremia is linked to poor clinical outcomes in patients with RA; however, no well-sized studies have evaluated the risk for osteoarticular infections and mortality outcomes in patients with RA following S aureus bacteremia.
• This Danish nationwide cohort study aimed to explore whether the cumulative incidence of osteoarticular infections and death would be higher in patients with RA than in those without RA after contracting S aureus bacteremia.
• The study cohort included 18,274 patients with a first episode of S aureus bacteremia between 2006 and 2018, of whom 367 had been diagnosed with RA before contracting S aureus bacteremia.
• The RA cohort had more women (62%) and a higher median age of participants (73 years) than the non-RA cohort (37% women; median age of participants, 70 years).

TAKEAWAY:

• The 90-day cumulative incidence of osteoarticular infections (septic arthritis, spondylitis, osteomyelitis, psoas muscle abscess, or prosthetic joint infection) was nearly double in patients with RA compared with in those without RA (23.1% vs 12.5%; hazard ratio [HR], 1.93; 95% CI, 1.54-2.41).
• In patients with RA, the risk for osteoarticular infections increased with tumor necrosis factor inhibitor use (HR, 2.27; 95% CI, 1.29-3.98) and orthopedic implants (HR, 1.75; 95% CI, 1.08-2.85).
• Moreover, 90-day all-cause mortality was comparable in the RA (35.4%) and non-RA cohorts (33.9%).

IN PRACTICE:

“Our findings stress the need for vigilance in patients with RA who present with S aureus bacteremia to ensure timely identification and treatment of osteoarticular infections, especially in current TNFi [tumor necrosis factor inhibitor] users and patients with orthopedic implants,” the authors wrote.

SOURCE:

This study, led by Sabine S. Dieperink, MD, of the Centre of Head and Orthopaedics, Copenhagen University Rigshospitalet Glostrup, Denmark, was published online March 9 in Rheumatology (Oxford).

LIMITATIONS:

There might have been chances of misclassification of metastatic S aureus infections owing to the lack of specificity in diagnoses or procedure codes. This study relied on administrative data to record osteoarticular infections, which might have led investigators to underestimate the true cumulative incidence of osteoarticular infections. Also, some patients might have passed away before being diagnosed with osteoarticular infection owing to the high mortality.

DISCLOSURES:

This work was supported by grants from The Danish Rheumatism Association and Beckett Fonden. Some of the authors, including the lead author, declared receiving grants from various funding agencies and other sources, including pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

After Staphylococcus aureus bacteremia, patients with rheumatoid arthritis (RA) face nearly double the risk for osteoarticular infections compared with those without RA, with similar mortality risks in both groups.

METHODOLOGY:

• The contraction of S aureus bacteremia is linked to poor clinical outcomes in patients with RA; however, no well-sized studies have evaluated the risk for osteoarticular infections and mortality outcomes in patients with RA following S aureus bacteremia.
• This Danish nationwide cohort study aimed to explore whether the cumulative incidence of osteoarticular infections and death would be higher in patients with RA than in those without RA after contracting S aureus bacteremia.
• The study cohort included 18,274 patients with a first episode of S aureus bacteremia between 2006 and 2018, of whom 367 had been diagnosed with RA before contracting S aureus bacteremia.
• The RA cohort had more women (62%) and a higher median age of participants (73 years) than the non-RA cohort (37% women; median age of participants, 70 years).

TAKEAWAY:

• The 90-day cumulative incidence of osteoarticular infections (septic arthritis, spondylitis, osteomyelitis, psoas muscle abscess, or prosthetic joint infection) was nearly double in patients with RA compared with in those without RA (23.1% vs 12.5%; hazard ratio [HR], 1.93; 95% CI, 1.54-2.41).
• In patients with RA, the risk for osteoarticular infections increased with tumor necrosis factor inhibitor use (HR, 2.27; 95% CI, 1.29-3.98) and orthopedic implants (HR, 1.75; 95% CI, 1.08-2.85).
• Moreover, 90-day all-cause mortality was comparable in the RA (35.4%) and non-RA cohorts (33.9%).

IN PRACTICE:

“Our findings stress the need for vigilance in patients with RA who present with S aureus bacteremia to ensure timely identification and treatment of osteoarticular infections, especially in current TNFi [tumor necrosis factor inhibitor] users and patients with orthopedic implants,” the authors wrote.

SOURCE:

This study, led by Sabine S. Dieperink, MD, of the Centre of Head and Orthopaedics, Copenhagen University Rigshospitalet Glostrup, Denmark, was published online March 9 in Rheumatology (Oxford).

LIMITATIONS:

There might have been chances of misclassification of metastatic S aureus infections owing to the lack of specificity in diagnoses or procedure codes. This study relied on administrative data to record osteoarticular infections, which might have led investigators to underestimate the true cumulative incidence of osteoarticular infections. Also, some patients might have passed away before being diagnosed with osteoarticular infection owing to the high mortality.

DISCLOSURES:

This work was supported by grants from The Danish Rheumatism Association and Beckett Fonden. Some of the authors, including the lead author, declared receiving grants from various funding agencies and other sources, including pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics. 

METHODOLOGY:

• Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.
• In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).
• The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.
• A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.
• A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.
• Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.
• When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.
• Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).

IN PRACTICE:

“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.

SOURCE:

The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and published online in Arthritis Care & Research

LIMITATIONS:

The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.

DISCLOSURES:

This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics. 

METHODOLOGY:

• Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.
• In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).
• The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.
• A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.
• A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.
• Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.
• When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.
• Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).

IN PRACTICE:

“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.

SOURCE:

The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and published online in Arthritis Care & Research

LIMITATIONS:

The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.

DISCLOSURES:

This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics. 

METHODOLOGY:

• Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.
• In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).
• The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.
• A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.
• A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.
• Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.
• When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.
• Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).

IN PRACTICE:

“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.

SOURCE:

The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and published online in Arthritis Care & Research

LIMITATIONS:

The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.

DISCLOSURES:

This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease.

For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.

More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes.

The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained.

But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery.
 

Xist Protein Complexes Make Male Mice Vulnerable to Lupus

In February, researchers Howard Chang, MD, PhD, and Diana Dou, PhD, of Stanford University in Stanford, California, made worldwide news when they published results from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.

Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.

When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.

By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”

The Stanford group sees the Xist protein complex, which they have studied extensively, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”
 

Faulty X Inactivation and Gene Escape

The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new.

About a decade ago, Montserrat Anguera, PhD, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus.

University of Pennsylvania

Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the silencing process was abnormal, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.

“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”

Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”

Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything.

Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.
 

Is It the Proteins, the RNA, or Both?

The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a 2022 paper that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.

Alexander Girgis

“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained Brendan Antiochos, MD. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, one recent study showed that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus.

Wes Linda

These findings led Erika Darrah, PhD, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said.

Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands. Xist, they found, was chock full of them. “Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.”

That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said.
 

Xist’s Other Functions

Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by Kathrin Plath, PhD, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview.

In 2021, Dr. Plath and her colleagues established in detail how Xist executes silencing, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”

Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can regulate gene expression in autosomes, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”

The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”

The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”

The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud.

What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”

Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease.

For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.

More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes.

The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained.

But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery.
 

Xist Protein Complexes Make Male Mice Vulnerable to Lupus

In February, researchers Howard Chang, MD, PhD, and Diana Dou, PhD, of Stanford University in Stanford, California, made worldwide news when they published results from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.

Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.

When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.

By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”

The Stanford group sees the Xist protein complex, which they have studied extensively, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”
 

Faulty X Inactivation and Gene Escape

The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new.

About a decade ago, Montserrat Anguera, PhD, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus.

University of Pennsylvania

Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the silencing process was abnormal, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.

“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”

Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”

Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything.

Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.
 

Is It the Proteins, the RNA, or Both?

The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a 2022 paper that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.

Alexander Girgis

“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained Brendan Antiochos, MD. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, one recent study showed that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus.

Wes Linda

These findings led Erika Darrah, PhD, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said.

Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands. Xist, they found, was chock full of them. “Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.”

That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said.
 

Xist’s Other Functions

Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by Kathrin Plath, PhD, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview.

In 2021, Dr. Plath and her colleagues established in detail how Xist executes silencing, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”

Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can regulate gene expression in autosomes, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”

The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”

The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”

The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud.

What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”

Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease.

For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.

More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes.

The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained.

But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery.
 

Xist Protein Complexes Make Male Mice Vulnerable to Lupus

In February, researchers Howard Chang, MD, PhD, and Diana Dou, PhD, of Stanford University in Stanford, California, made worldwide news when they published results from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.

Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.

When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.

By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”

The Stanford group sees the Xist protein complex, which they have studied extensively, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”
 

Faulty X Inactivation and Gene Escape

The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new.

About a decade ago, Montserrat Anguera, PhD, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus.

University of Pennsylvania

Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the silencing process was abnormal, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.

“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”

Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”

Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything.

Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.
 

Is It the Proteins, the RNA, or Both?

The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a 2022 paper that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.

Alexander Girgis

“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained Brendan Antiochos, MD. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, one recent study showed that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus.

Wes Linda

These findings led Erika Darrah, PhD, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said.

Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands. Xist, they found, was chock full of them. “Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.”

That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said.
 

Xist’s Other Functions

Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by Kathrin Plath, PhD, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview.

In 2021, Dr. Plath and her colleagues established in detail how Xist executes silencing, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”

Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can regulate gene expression in autosomes, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”

The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”

The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”

The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud.

What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”

CORRECTED April 16, 2024 // An earlier version of this article stated incorrect percentages of patients who never received any biologics during the study's 3-year period but improved rapidly or moderately.

Early initiation of biologics — within the first 2 months of symptom presentation — appears to have a significant impact on how rapidly patients with juvenile idiopathic arthritis (JIA) improve, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

“Our study provides evidence that early use of biologics can significantly alter the disease trajectory of patients with JIA,” Mei-Sing Ong, PhD, of Harvard Medical School, Boston, told attendees. At the same time, however, not all patients who improved rapidly during a 3-year follow-up period needed biologics, a finding that Ong said the researchers are continuing to investigate.

Marinka Twilt, MD, MScE, PhD, chair of CARRA’s JIA Research Committee and a pediatric rheumatologist and clinician scientist at Alberta Children’s Hospital in Calgary, Canada, was not involved in the research but said the continued sustained remission in patients who improved rapidly is very reassuring.

Dr. Twilt

“We always wonder if initial response will be sustained or if patients tend to flare after the initial treatment,” Dr. Twilt told this news organization. “To see the sustained response up to 3 years is fantastic.” She added that it would be enlightening to see more information about patients who rapidly improved over 3 years, including whether they were still taking a [conventional disease-modifying antirheumatic drug (DMARD)] and/or biologic.

“A new diagnosis can be overwhelming for families, and this sometimes leads to step-up therapy to not overwhelm them more with information on new drugs,” Dr. Twilt said. “This study shows that an earlier start is beneficial, and this should be discussed with families early on so there is less delay in early treatment.”

Canada and many US states currently require 3 months of conventional DMARD treatment before patients can start a biologic, Dr. Twilt said, yet “this study shows the additive benefit of using a biologic within 2 months of starting a DMARD, which hopefully will lead to insurance companies adopting this threshold.”

The STOP-JIA study is a prospective observational study that compares the effectiveness of three different treatment plans for JIA. A Step-Up cohort of 257 patients received conventional antirheumatic monotherapy initially, with a biologic added at 3 months or later as needed. The Early Combination cohort of 100 patients received conventional antirheumatic therapy with a biologic from the start. The Biologic First cohort of 43 patients began taking a biologic as a first-line therapy.

In previously reported results of the study at 12 months’ follow-up, there was no significant difference between the Step-Up and Biologic First groups, but there were significant differences between the Step-Up and Early Combination groups. Significantly more patients in the Early Combination group (58.8%) than in the Step-Up group (42.8%) had inactive disease, based on the clinical Juvenile Arthritis Disease Activity Score 10 (cJADAS-10) (P = .03). Similarly, 81% of Early Combination patients achieved the American College of Rheumatology 70% improvement criteria, compared with 62% of the Step-Up patients (P = .01).

To learn whether the timing of starting a biologic influenced the disease trajectory over time, the researchers compared subgroups of patients with similar trajectories.

“Assessing treatment outcomes at a single point in time does not give us a complete picture of the effects of treatment on disease trajectory, which is an important outcome given that JIA is characterized by a relapsing-remitting course,” Dr. Ong told attendees.

Patients were sorted in the slow, moderate, or rapid improvement trajectories. In previously reported data at 12 months’ follow-up, patients’ odds of achieving rapid improvement were 3.6 times greater if they had started a biologic within 3 months.

This study compared patients’ trajectories over 3 years in the 259 patients (65% of the original cohort) who had at least one cJADAS-10 assessment in each year of follow-up. Most patients (66.8%) were in the rapid improvement class, with 25.9% in the moderate improvement class and 7.3% in the slow improvement class.

Patients in the rapid improvement group achieved inactive disease (cJADAS-10 of 2.5 or less) within 1 year and maintained inactive disease through the second and third years. The moderate and low improvement groups both had higher disease activity at baseline, but the moderate group continued to improve in years 2 and 3, with minimal disease by year 3, on the basis of the cJADAS-10 scores of 2.5-5. The slow group continued to experience moderate disease activity during years 2 and 3.

The findings also revealed that the earlier patients began a biologic, the more likely they were to be in the rapid improvement group than the slow improvement group. Participants who started a biologic in the first month had more than five times greater odds of being in the rapid improvement group than in the slow improvement group (odds ratio [OR], 5.33; P = .017).

Those who started a biologic in the second month were also more likely to be in the rapid improvement group (OR, 2.67; P = .032). For those who began a biologic by the third month, the odds of improving rapidly were not statistically significant, though Ong noted that could have been because of the small sample size. There was also no significant difference between those who improved moderately vs slowly based on when a biologic was initiated.

It would be helpful to learn whether any of the patients in the rapid improvement group were able to stop medications or whether they all continued treatment during the 3 years of follow-up, Dr. Twilt said. “Does early treatment with biologics not only lead to early remission after initiation but also to the possibility of stopping treatment earlier and remaining in remission?” she asked.

The researchers also found that not all patients needed biologics to end up in the rapid improvement group. Among patients who never received any biologics during the 3-year period, 83% improved rapidly and 17% improved moderately. Yet the researchers identified no significant differences in demographics or clinical factors between patients who received biologics and those who did not.

“The fact that there is a group of patients in the rapid response group who never need a biologic is of great interest, as we always want to treat patients early with the medications they need, but we also want to avoid overtreating patients,” Dr. Twilt said. It’s important to find out what differentiates those patients and whether it is possible to predict which patients do not need biologics early on, she said.

Dr. Ong said the research team is working to develop machine learning methods to improve risk stratification in hopes of addressing that question.

Dr. Ong and Dr. Twilt reported no disclosures. The research was funded by CARRA and the Patient-Centered Outcomes Research Institute.
 

A version of this article appeared on Medscape.com .

CORRECTED April 16, 2024 // An earlier version of this article stated incorrect percentages of patients who never received any biologics during the study's 3-year period but improved rapidly or moderately.

Early initiation of biologics — within the first 2 months of symptom presentation — appears to have a significant impact on how rapidly patients with juvenile idiopathic arthritis (JIA) improve, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

“Our study provides evidence that early use of biologics can significantly alter the disease trajectory of patients with JIA,” Mei-Sing Ong, PhD, of Harvard Medical School, Boston, told attendees. At the same time, however, not all patients who improved rapidly during a 3-year follow-up period needed biologics, a finding that Ong said the researchers are continuing to investigate.

Marinka Twilt, MD, MScE, PhD, chair of CARRA’s JIA Research Committee and a pediatric rheumatologist and clinician scientist at Alberta Children’s Hospital in Calgary, Canada, was not involved in the research but said the continued sustained remission in patients who improved rapidly is very reassuring.

Dr. Twilt

“We always wonder if initial response will be sustained or if patients tend to flare after the initial treatment,” Dr. Twilt told this news organization. “To see the sustained response up to 3 years is fantastic.” She added that it would be enlightening to see more information about patients who rapidly improved over 3 years, including whether they were still taking a [conventional disease-modifying antirheumatic drug (DMARD)] and/or biologic.

“A new diagnosis can be overwhelming for families, and this sometimes leads to step-up therapy to not overwhelm them more with information on new drugs,” Dr. Twilt said. “This study shows that an earlier start is beneficial, and this should be discussed with families early on so there is less delay in early treatment.”

Canada and many US states currently require 3 months of conventional DMARD treatment before patients can start a biologic, Dr. Twilt said, yet “this study shows the additive benefit of using a biologic within 2 months of starting a DMARD, which hopefully will lead to insurance companies adopting this threshold.”

The STOP-JIA study is a prospective observational study that compares the effectiveness of three different treatment plans for JIA. A Step-Up cohort of 257 patients received conventional antirheumatic monotherapy initially, with a biologic added at 3 months or later as needed. The Early Combination cohort of 100 patients received conventional antirheumatic therapy with a biologic from the start. The Biologic First cohort of 43 patients began taking a biologic as a first-line therapy.

In previously reported results of the study at 12 months’ follow-up, there was no significant difference between the Step-Up and Biologic First groups, but there were significant differences between the Step-Up and Early Combination groups. Significantly more patients in the Early Combination group (58.8%) than in the Step-Up group (42.8%) had inactive disease, based on the clinical Juvenile Arthritis Disease Activity Score 10 (cJADAS-10) (P = .03). Similarly, 81% of Early Combination patients achieved the American College of Rheumatology 70% improvement criteria, compared with 62% of the Step-Up patients (P = .01).

To learn whether the timing of starting a biologic influenced the disease trajectory over time, the researchers compared subgroups of patients with similar trajectories.

“Assessing treatment outcomes at a single point in time does not give us a complete picture of the effects of treatment on disease trajectory, which is an important outcome given that JIA is characterized by a relapsing-remitting course,” Dr. Ong told attendees.

Patients were sorted in the slow, moderate, or rapid improvement trajectories. In previously reported data at 12 months’ follow-up, patients’ odds of achieving rapid improvement were 3.6 times greater if they had started a biologic within 3 months.

This study compared patients’ trajectories over 3 years in the 259 patients (65% of the original cohort) who had at least one cJADAS-10 assessment in each year of follow-up. Most patients (66.8%) were in the rapid improvement class, with 25.9% in the moderate improvement class and 7.3% in the slow improvement class.

Patients in the rapid improvement group achieved inactive disease (cJADAS-10 of 2.5 or less) within 1 year and maintained inactive disease through the second and third years. The moderate and low improvement groups both had higher disease activity at baseline, but the moderate group continued to improve in years 2 and 3, with minimal disease by year 3, on the basis of the cJADAS-10 scores of 2.5-5. The slow group continued to experience moderate disease activity during years 2 and 3.

The findings also revealed that the earlier patients began a biologic, the more likely they were to be in the rapid improvement group than the slow improvement group. Participants who started a biologic in the first month had more than five times greater odds of being in the rapid improvement group than in the slow improvement group (odds ratio [OR], 5.33; P = .017).

Those who started a biologic in the second month were also more likely to be in the rapid improvement group (OR, 2.67; P = .032). For those who began a biologic by the third month, the odds of improving rapidly were not statistically significant, though Ong noted that could have been because of the small sample size. There was also no significant difference between those who improved moderately vs slowly based on when a biologic was initiated.

It would be helpful to learn whether any of the patients in the rapid improvement group were able to stop medications or whether they all continued treatment during the 3 years of follow-up, Dr. Twilt said. “Does early treatment with biologics not only lead to early remission after initiation but also to the possibility of stopping treatment earlier and remaining in remission?” she asked.

The researchers also found that not all patients needed biologics to end up in the rapid improvement group. Among patients who never received any biologics during the 3-year period, 83% improved rapidly and 17% improved moderately. Yet the researchers identified no significant differences in demographics or clinical factors between patients who received biologics and those who did not.

“The fact that there is a group of patients in the rapid response group who never need a biologic is of great interest, as we always want to treat patients early with the medications they need, but we also want to avoid overtreating patients,” Dr. Twilt said. It’s important to find out what differentiates those patients and whether it is possible to predict which patients do not need biologics early on, she said.

Dr. Ong said the research team is working to develop machine learning methods to improve risk stratification in hopes of addressing that question.

Dr. Ong and Dr. Twilt reported no disclosures. The research was funded by CARRA and the Patient-Centered Outcomes Research Institute.
 

A version of this article appeared on Medscape.com .

CORRECTED April 16, 2024 // An earlier version of this article stated incorrect percentages of patients who never received any biologics during the study's 3-year period but improved rapidly or moderately.

Early initiation of biologics — within the first 2 months of symptom presentation — appears to have a significant impact on how rapidly patients with juvenile idiopathic arthritis (JIA) improve, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

“Our study provides evidence that early use of biologics can significantly alter the disease trajectory of patients with JIA,” Mei-Sing Ong, PhD, of Harvard Medical School, Boston, told attendees. At the same time, however, not all patients who improved rapidly during a 3-year follow-up period needed biologics, a finding that Ong said the researchers are continuing to investigate.

Marinka Twilt, MD, MScE, PhD, chair of CARRA’s JIA Research Committee and a pediatric rheumatologist and clinician scientist at Alberta Children’s Hospital in Calgary, Canada, was not involved in the research but said the continued sustained remission in patients who improved rapidly is very reassuring.

Dr. Twilt

“We always wonder if initial response will be sustained or if patients tend to flare after the initial treatment,” Dr. Twilt told this news organization. “To see the sustained response up to 3 years is fantastic.” She added that it would be enlightening to see more information about patients who rapidly improved over 3 years, including whether they were still taking a [conventional disease-modifying antirheumatic drug (DMARD)] and/or biologic.

“A new diagnosis can be overwhelming for families, and this sometimes leads to step-up therapy to not overwhelm them more with information on new drugs,” Dr. Twilt said. “This study shows that an earlier start is beneficial, and this should be discussed with families early on so there is less delay in early treatment.”

Canada and many US states currently require 3 months of conventional DMARD treatment before patients can start a biologic, Dr. Twilt said, yet “this study shows the additive benefit of using a biologic within 2 months of starting a DMARD, which hopefully will lead to insurance companies adopting this threshold.”

The STOP-JIA study is a prospective observational study that compares the effectiveness of three different treatment plans for JIA. A Step-Up cohort of 257 patients received conventional antirheumatic monotherapy initially, with a biologic added at 3 months or later as needed. The Early Combination cohort of 100 patients received conventional antirheumatic therapy with a biologic from the start. The Biologic First cohort of 43 patients began taking a biologic as a first-line therapy.

In previously reported results of the study at 12 months’ follow-up, there was no significant difference between the Step-Up and Biologic First groups, but there were significant differences between the Step-Up and Early Combination groups. Significantly more patients in the Early Combination group (58.8%) than in the Step-Up group (42.8%) had inactive disease, based on the clinical Juvenile Arthritis Disease Activity Score 10 (cJADAS-10) (P = .03). Similarly, 81% of Early Combination patients achieved the American College of Rheumatology 70% improvement criteria, compared with 62% of the Step-Up patients (P = .01).

To learn whether the timing of starting a biologic influenced the disease trajectory over time, the researchers compared subgroups of patients with similar trajectories.

“Assessing treatment outcomes at a single point in time does not give us a complete picture of the effects of treatment on disease trajectory, which is an important outcome given that JIA is characterized by a relapsing-remitting course,” Dr. Ong told attendees.

Patients were sorted in the slow, moderate, or rapid improvement trajectories. In previously reported data at 12 months’ follow-up, patients’ odds of achieving rapid improvement were 3.6 times greater if they had started a biologic within 3 months.

This study compared patients’ trajectories over 3 years in the 259 patients (65% of the original cohort) who had at least one cJADAS-10 assessment in each year of follow-up. Most patients (66.8%) were in the rapid improvement class, with 25.9% in the moderate improvement class and 7.3% in the slow improvement class.

Patients in the rapid improvement group achieved inactive disease (cJADAS-10 of 2.5 or less) within 1 year and maintained inactive disease through the second and third years. The moderate and low improvement groups both had higher disease activity at baseline, but the moderate group continued to improve in years 2 and 3, with minimal disease by year 3, on the basis of the cJADAS-10 scores of 2.5-5. The slow group continued to experience moderate disease activity during years 2 and 3.

The findings also revealed that the earlier patients began a biologic, the more likely they were to be in the rapid improvement group than the slow improvement group. Participants who started a biologic in the first month had more than five times greater odds of being in the rapid improvement group than in the slow improvement group (odds ratio [OR], 5.33; P = .017).

Those who started a biologic in the second month were also more likely to be in the rapid improvement group (OR, 2.67; P = .032). For those who began a biologic by the third month, the odds of improving rapidly were not statistically significant, though Ong noted that could have been because of the small sample size. There was also no significant difference between those who improved moderately vs slowly based on when a biologic was initiated.

It would be helpful to learn whether any of the patients in the rapid improvement group were able to stop medications or whether they all continued treatment during the 3 years of follow-up, Dr. Twilt said. “Does early treatment with biologics not only lead to early remission after initiation but also to the possibility of stopping treatment earlier and remaining in remission?” she asked.

The researchers also found that not all patients needed biologics to end up in the rapid improvement group. Among patients who never received any biologics during the 3-year period, 83% improved rapidly and 17% improved moderately. Yet the researchers identified no significant differences in demographics or clinical factors between patients who received biologics and those who did not.

“The fact that there is a group of patients in the rapid response group who never need a biologic is of great interest, as we always want to treat patients early with the medications they need, but we also want to avoid overtreating patients,” Dr. Twilt said. It’s important to find out what differentiates those patients and whether it is possible to predict which patients do not need biologics early on, she said.

Dr. Ong said the research team is working to develop machine learning methods to improve risk stratification in hopes of addressing that question.

Dr. Ong and Dr. Twilt reported no disclosures. The research was funded by CARRA and the Patient-Centered Outcomes Research Institute.
 

A version of this article appeared on Medscape.com .

An estimated 3% of the world’s population have psoriasis, with approximately 6.4 million people across Europe affected. Almost one third of people with psoriasis will develop psoriatic arthritis (PsA), a disease that can be severe and debilitating and lead to irreversible degeneration of bone and tissue, typically affecting the joints of hands and feet. 

As inflammatory autoimmune diseases, psoriasis and PsA also increase the risk for further comorbidities, such as cardiovascular diseases and obesity, with higher rates of depression among those affected. 

Although notable advances have been made in the range of treatment options for PsA, it remains difficult to diagnose. No specific diagnostic criteria or laboratory tests are available, and the disease course and response to treatment can be unpredictable.

“Another key unmet need relates to whether we can reliably identify risk factors for which a person with psoriasis will develop PsA. We know that 30% will develop PsA, but we cannot identify which person with psoriasis is at risk,” said Professor Oliver FitzGerald of University College Dublin (UCD), Dublin, Ireland, an international opinion leader in rheumatology. A clearer understanding of PsA could lead to development of tools for its early diagnosis and identification of disease prevention strategies, he explained.

Thus, HIPPOCRATES (Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States ) was created. This ambitious research consortium was conceived by Dr. FitzGerald and his colleague Stephen Pennington, professor of proteomics at UCD, together with a number of likeminded colleagues in the fields of rheumatology and dermatology and at organizations such as GRAPPA, HUPO, EULAR, and EUROPSO. 

The collaboration has brought together world-leading clinicians, researchers, and people living with psoriasis and PsA to address the main challenges in its early identification and management.

HIPPOCRATES received €23.5 million in funding from the EU Innovative Medicines Initiative public-private partnership in 2021 and is now half way through its 5-year plan. 

Key Goals 

HIPPOCRATES involves 27 partners, including from industry, in 11 countries. 

Its four key goals are:

• Identifying specific PsA disease markers to develop accurate diagnostic tools;
• Developing prediction strategies to identify which person with psoriasis will develop PsA;
• Monitoring and prevention of PsA disease progression to irreversible joint damage; and
• Identifying personalized treatment options, so that patients are treated with the right medicines for their specific disease.

“The pharmaceutical companies have come up with a veritable armory of potential treatments, but rheumatologists still don’t know which one to use for a particular patient at a particular time,” Dr. Pennington explained to this news organization. “So the reality is they tend to cycle through treatments until they find one that is effective.” This is not very efficient or desirable for patients, he added. 

Multidisciplinary Approach

A key advantage of HIPPOCRATES is that it brings several medical disciplines together. The current approach of clinicians working in silos is a key barrier to earlier diagnosis of PsA.

“The reality is that a patient with psoriasis will see a dermatologist, and dermatologists don’t necessarily have the skills or training to identify the very early stages of psoriatic arthritis, so they will only refer a patient of theirs to a rheumatologist at a very late stage,” said Dr. Pennington.

Dermatologists need better tools to be able to recognize when they should refer their psoriasis patients to rheumatologists, so that patients developing PsA are diagnosed and treated earlier, he explained. 

GPs will also be an important component of the project because they are the first point of healthcare contact for people with PsA or psoriasis.

“[I]t is about helping GPs diagnose earlier and raise awareness among patients. Historically, there has been a bit of a lag between people having their first symptoms and getting a diagnosis,” explained HIPPOCRATES collaborator Frances Mair, the Norie Miller Professor of General Practice and head of general practice and primary care at the University of Glasgow, Glasgow, Scotland. 

Dr. Mair said that diagnosis isn't always straightforward, and the hope is that the study will identify more specific risk factors that will help GPs flag PsA earlier. 

Patient Involvement and Data Sharing

The HIPPOCRATES consortium involves patients in all stages of the project.

“In HIPPOCRATES, patient and public involvement is really a central feature, which is quite unusual at the more experimental side of healthcare and research. In HIPPOCRATES, the patient research partners have a leading role, making a real difference…” said Dr. Mair.

To facilitate its goals, the consortium partners are sharing data and samples from previously conducted studies on psoriasis and PsA populations. This will facilitate extensive omics-based analyses to establish and validate robust biomarkers across datasets, using the latest cutting-edge techniques, including machine learning and artificial intelligence. 

In addition, the HIPPOCRATES Prospective Observational Study (HPOS) was launched last year. This web-based study aims to recruit 25,000 adults (≥ 18 years of age) with skin psoriasis across Europe. They will collect their clinical data every 6 months, including emerging musculoskeletal symptoms. Blood samples will also be collected remotely from a subset of 3000 participants using a finger-prick kit that will be posted to their homes. 

HPOS has already commenced recruitment in the UK, Ireland and, most recently, Greece and Portugal, with nearly 2300 participants enrolled to date. HPOS also plans to launch in France, Italy, Spain, Denmark, Germany, Belgium, the Netherlands, and Sweden. 

“This ambitious study will give us the statistical power to identify clinical/molecular risk factors for progression from psoriasis to PsA. We anticipate that 675 participants per year will develop PsA in our studied population. Participants will receive regular feedback to help monitor their condition, and we will help them to get the medical care that they need,” said Dr. FitzGerald.

Dr. Pennington added that the consortium believes it is a “realistic goal” that the resulting molecular risk prediction tools could eventually enable clinicians to intervene to prevent PsA. 

From Research to Practice

The HIPPOCRATES projects are making good progress, with several early publications, and further publications being drafted. 

“One of the biggest achievements so far has been to assemble this massive resource of patient samples — tens of thousands in total in a single integrated database, which is the foundation of the project,” said Dr. Pennington. He explained that it took a significant amount of work to secure the necessary agreements from all 27 partners to share the patient data securely, appropriately, and anonymously within the consortium.

Creating successful biomarkers, algorithms, and other tools is one thing, but disseminating the knowledge learned and rolling out the final agreed guidelines will be just as important as the research work, said Dr. Pennington.

Dr. Mair, who is responsible for promoting communication, dissemination, and maximizing the impact of the research undertaken by the HIPPOCRATES consortium, said: “We see so often in healthcare that people come with great ideas or tools, yet they don’t become part of everyday practice. Hence, I am working on the implementation side of HIPPOCRATES, to make sure its findings will be embedded and routinely used in practice,” she said.

A version of this article appeared on Medscape.com.

An estimated 3% of the world’s population have psoriasis, with approximately 6.4 million people across Europe affected. Almost one third of people with psoriasis will develop psoriatic arthritis (PsA), a disease that can be severe and debilitating and lead to irreversible degeneration of bone and tissue, typically affecting the joints of hands and feet. 

As inflammatory autoimmune diseases, psoriasis and PsA also increase the risk for further comorbidities, such as cardiovascular diseases and obesity, with higher rates of depression among those affected. 

Although notable advances have been made in the range of treatment options for PsA, it remains difficult to diagnose. No specific diagnostic criteria or laboratory tests are available, and the disease course and response to treatment can be unpredictable.

“Another key unmet need relates to whether we can reliably identify risk factors for which a person with psoriasis will develop PsA. We know that 30% will develop PsA, but we cannot identify which person with psoriasis is at risk,” said Professor Oliver FitzGerald of University College Dublin (UCD), Dublin, Ireland, an international opinion leader in rheumatology. A clearer understanding of PsA could lead to development of tools for its early diagnosis and identification of disease prevention strategies, he explained.

Thus, HIPPOCRATES (Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States ) was created. This ambitious research consortium was conceived by Dr. FitzGerald and his colleague Stephen Pennington, professor of proteomics at UCD, together with a number of likeminded colleagues in the fields of rheumatology and dermatology and at organizations such as GRAPPA, HUPO, EULAR, and EUROPSO. 

The collaboration has brought together world-leading clinicians, researchers, and people living with psoriasis and PsA to address the main challenges in its early identification and management.

HIPPOCRATES received €23.5 million in funding from the EU Innovative Medicines Initiative public-private partnership in 2021 and is now half way through its 5-year plan. 

Key Goals 

HIPPOCRATES involves 27 partners, including from industry, in 11 countries. 

Its four key goals are:

• Identifying specific PsA disease markers to develop accurate diagnostic tools;
• Developing prediction strategies to identify which person with psoriasis will develop PsA;
• Monitoring and prevention of PsA disease progression to irreversible joint damage; and
• Identifying personalized treatment options, so that patients are treated with the right medicines for their specific disease.

“The pharmaceutical companies have come up with a veritable armory of potential treatments, but rheumatologists still don’t know which one to use for a particular patient at a particular time,” Dr. Pennington explained to this news organization. “So the reality is they tend to cycle through treatments until they find one that is effective.” This is not very efficient or desirable for patients, he added. 

Multidisciplinary Approach

A key advantage of HIPPOCRATES is that it brings several medical disciplines together. The current approach of clinicians working in silos is a key barrier to earlier diagnosis of PsA.

“The reality is that a patient with psoriasis will see a dermatologist, and dermatologists don’t necessarily have the skills or training to identify the very early stages of psoriatic arthritis, so they will only refer a patient of theirs to a rheumatologist at a very late stage,” said Dr. Pennington.

Dermatologists need better tools to be able to recognize when they should refer their psoriasis patients to rheumatologists, so that patients developing PsA are diagnosed and treated earlier, he explained. 

GPs will also be an important component of the project because they are the first point of healthcare contact for people with PsA or psoriasis.

“[I]t is about helping GPs diagnose earlier and raise awareness among patients. Historically, there has been a bit of a lag between people having their first symptoms and getting a diagnosis,” explained HIPPOCRATES collaborator Frances Mair, the Norie Miller Professor of General Practice and head of general practice and primary care at the University of Glasgow, Glasgow, Scotland. 

Dr. Mair said that diagnosis isn't always straightforward, and the hope is that the study will identify more specific risk factors that will help GPs flag PsA earlier. 

Patient Involvement and Data Sharing

The HIPPOCRATES consortium involves patients in all stages of the project.

“In HIPPOCRATES, patient and public involvement is really a central feature, which is quite unusual at the more experimental side of healthcare and research. In HIPPOCRATES, the patient research partners have a leading role, making a real difference…” said Dr. Mair.

To facilitate its goals, the consortium partners are sharing data and samples from previously conducted studies on psoriasis and PsA populations. This will facilitate extensive omics-based analyses to establish and validate robust biomarkers across datasets, using the latest cutting-edge techniques, including machine learning and artificial intelligence. 

In addition, the HIPPOCRATES Prospective Observational Study (HPOS) was launched last year. This web-based study aims to recruit 25,000 adults (≥ 18 years of age) with skin psoriasis across Europe. They will collect their clinical data every 6 months, including emerging musculoskeletal symptoms. Blood samples will also be collected remotely from a subset of 3000 participants using a finger-prick kit that will be posted to their homes. 

HPOS has already commenced recruitment in the UK, Ireland and, most recently, Greece and Portugal, with nearly 2300 participants enrolled to date. HPOS also plans to launch in France, Italy, Spain, Denmark, Germany, Belgium, the Netherlands, and Sweden. 

“This ambitious study will give us the statistical power to identify clinical/molecular risk factors for progression from psoriasis to PsA. We anticipate that 675 participants per year will develop PsA in our studied population. Participants will receive regular feedback to help monitor their condition, and we will help them to get the medical care that they need,” said Dr. FitzGerald.

Dr. Pennington added that the consortium believes it is a “realistic goal” that the resulting molecular risk prediction tools could eventually enable clinicians to intervene to prevent PsA. 

From Research to Practice

The HIPPOCRATES projects are making good progress, with several early publications, and further publications being drafted. 

“One of the biggest achievements so far has been to assemble this massive resource of patient samples — tens of thousands in total in a single integrated database, which is the foundation of the project,” said Dr. Pennington. He explained that it took a significant amount of work to secure the necessary agreements from all 27 partners to share the patient data securely, appropriately, and anonymously within the consortium.

Creating successful biomarkers, algorithms, and other tools is one thing, but disseminating the knowledge learned and rolling out the final agreed guidelines will be just as important as the research work, said Dr. Pennington.

Dr. Mair, who is responsible for promoting communication, dissemination, and maximizing the impact of the research undertaken by the HIPPOCRATES consortium, said: “We see so often in healthcare that people come with great ideas or tools, yet they don’t become part of everyday practice. Hence, I am working on the implementation side of HIPPOCRATES, to make sure its findings will be embedded and routinely used in practice,” she said.

A version of this article appeared on Medscape.com.

An estimated 3% of the world’s population have psoriasis, with approximately 6.4 million people across Europe affected. Almost one third of people with psoriasis will develop psoriatic arthritis (PsA), a disease that can be severe and debilitating and lead to irreversible degeneration of bone and tissue, typically affecting the joints of hands and feet. 

As inflammatory autoimmune diseases, psoriasis and PsA also increase the risk for further comorbidities, such as cardiovascular diseases and obesity, with higher rates of depression among those affected. 

Although notable advances have been made in the range of treatment options for PsA, it remains difficult to diagnose. No specific diagnostic criteria or laboratory tests are available, and the disease course and response to treatment can be unpredictable.

“Another key unmet need relates to whether we can reliably identify risk factors for which a person with psoriasis will develop PsA. We know that 30% will develop PsA, but we cannot identify which person with psoriasis is at risk,” said Professor Oliver FitzGerald of University College Dublin (UCD), Dublin, Ireland, an international opinion leader in rheumatology. A clearer understanding of PsA could lead to development of tools for its early diagnosis and identification of disease prevention strategies, he explained.

Thus, HIPPOCRATES (Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States ) was created. This ambitious research consortium was conceived by Dr. FitzGerald and his colleague Stephen Pennington, professor of proteomics at UCD, together with a number of likeminded colleagues in the fields of rheumatology and dermatology and at organizations such as GRAPPA, HUPO, EULAR, and EUROPSO. 

The collaboration has brought together world-leading clinicians, researchers, and people living with psoriasis and PsA to address the main challenges in its early identification and management.

HIPPOCRATES received €23.5 million in funding from the EU Innovative Medicines Initiative public-private partnership in 2021 and is now half way through its 5-year plan. 

Key Goals 

HIPPOCRATES involves 27 partners, including from industry, in 11 countries. 

Its four key goals are:

• Identifying specific PsA disease markers to develop accurate diagnostic tools;
• Developing prediction strategies to identify which person with psoriasis will develop PsA;
• Monitoring and prevention of PsA disease progression to irreversible joint damage; and
• Identifying personalized treatment options, so that patients are treated with the right medicines for their specific disease.

“The pharmaceutical companies have come up with a veritable armory of potential treatments, but rheumatologists still don’t know which one to use for a particular patient at a particular time,” Dr. Pennington explained to this news organization. “So the reality is they tend to cycle through treatments until they find one that is effective.” This is not very efficient or desirable for patients, he added. 

Multidisciplinary Approach

A key advantage of HIPPOCRATES is that it brings several medical disciplines together. The current approach of clinicians working in silos is a key barrier to earlier diagnosis of PsA.

“The reality is that a patient with psoriasis will see a dermatologist, and dermatologists don’t necessarily have the skills or training to identify the very early stages of psoriatic arthritis, so they will only refer a patient of theirs to a rheumatologist at a very late stage,” said Dr. Pennington.

Dermatologists need better tools to be able to recognize when they should refer their psoriasis patients to rheumatologists, so that patients developing PsA are diagnosed and treated earlier, he explained. 

GPs will also be an important component of the project because they are the first point of healthcare contact for people with PsA or psoriasis.

“[I]t is about helping GPs diagnose earlier and raise awareness among patients. Historically, there has been a bit of a lag between people having their first symptoms and getting a diagnosis,” explained HIPPOCRATES collaborator Frances Mair, the Norie Miller Professor of General Practice and head of general practice and primary care at the University of Glasgow, Glasgow, Scotland. 

Dr. Mair said that diagnosis isn't always straightforward, and the hope is that the study will identify more specific risk factors that will help GPs flag PsA earlier. 

Patient Involvement and Data Sharing

The HIPPOCRATES consortium involves patients in all stages of the project.

“In HIPPOCRATES, patient and public involvement is really a central feature, which is quite unusual at the more experimental side of healthcare and research. In HIPPOCRATES, the patient research partners have a leading role, making a real difference…” said Dr. Mair.

To facilitate its goals, the consortium partners are sharing data and samples from previously conducted studies on psoriasis and PsA populations. This will facilitate extensive omics-based analyses to establish and validate robust biomarkers across datasets, using the latest cutting-edge techniques, including machine learning and artificial intelligence. 

In addition, the HIPPOCRATES Prospective Observational Study (HPOS) was launched last year. This web-based study aims to recruit 25,000 adults (≥ 18 years of age) with skin psoriasis across Europe. They will collect their clinical data every 6 months, including emerging musculoskeletal symptoms. Blood samples will also be collected remotely from a subset of 3000 participants using a finger-prick kit that will be posted to their homes. 

HPOS has already commenced recruitment in the UK, Ireland and, most recently, Greece and Portugal, with nearly 2300 participants enrolled to date. HPOS also plans to launch in France, Italy, Spain, Denmark, Germany, Belgium, the Netherlands, and Sweden. 

“This ambitious study will give us the statistical power to identify clinical/molecular risk factors for progression from psoriasis to PsA. We anticipate that 675 participants per year will develop PsA in our studied population. Participants will receive regular feedback to help monitor their condition, and we will help them to get the medical care that they need,” said Dr. FitzGerald.

Dr. Pennington added that the consortium believes it is a “realistic goal” that the resulting molecular risk prediction tools could eventually enable clinicians to intervene to prevent PsA. 

From Research to Practice

The HIPPOCRATES projects are making good progress, with several early publications, and further publications being drafted. 

“One of the biggest achievements so far has been to assemble this massive resource of patient samples — tens of thousands in total in a single integrated database, which is the foundation of the project,” said Dr. Pennington. He explained that it took a significant amount of work to secure the necessary agreements from all 27 partners to share the patient data securely, appropriately, and anonymously within the consortium.

Creating successful biomarkers, algorithms, and other tools is one thing, but disseminating the knowledge learned and rolling out the final agreed guidelines will be just as important as the research work, said Dr. Pennington.

Dr. Mair, who is responsible for promoting communication, dissemination, and maximizing the impact of the research undertaken by the HIPPOCRATES consortium, said: “We see so often in healthcare that people come with great ideas or tools, yet they don’t become part of everyday practice. Hence, I am working on the implementation side of HIPPOCRATES, to make sure its findings will be embedded and routinely used in practice,” she said.

A version of this article appeared on Medscape.com.

The accumulation of multiple adverse social determinants of health is linked to worse disease at initial presentation and worse disease activity over time in children with rheumatologic conditions, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

One study revealed that cumulative factors conferring social disadvantage progressively increased the odds of active disease and functional disability in children with juvenile idiopathic arthritis (JIA). Another study similarly found that children with lupus living in neighborhoods with comparatively fewer resources for childhood opportunity had worse disease at presentation and greater disease activity over follow-up.

The findings suggest that exposure to multiple disadvantaging social variables may be linked to worse outcomes than exposure to any single factor, William Daniel Soulsby, MD, of the University of California San Francisco, told attendees in his presentation of data from the JIA study.

“Most prior studies have analyzed such determinants as independent risk factors,” Dr. Soulsby said. “However, individuals experiencing social disadvantage often face multiple social hardships that rarely act in isolation; studying these factors independently may miss underlying disparities.”

Stacy P. Ardoin, MD, MSc, professor of pediatric and adult rheumatology at Nationwide Children’s Hospital and The Ohio State University in Columbus, and vice president of CARRA, did not find the results of Soulsby’s study surprising, but she said they do “provide important confirmation of our growing understanding of the impact of social determinants of health on the outcomes of children and adolescents with chronic disease like juvenile idiopathic arthritis.” She added: “In medicine, we often think about the bench, the bedside, and the clinic, but this study tells us that if we want to improve outcomes for our patients, we also need to think about the ‘backyard,’ too.”
 

Social Disadvantage With JIA

Dr. Soulsby’s team adopted an approach similar to that of a recent National Survey of Children’s Health analysis that used a combined scoring system to calculate cumulative social disadvantage. The researchers used income level, insurance status, and education level to capture individual factors related to disadvantage and then an area deprivation index (ADI) to capture community factors. While they were unable to use any variables specific to societal factors, they included race, which is relevant at all three levels.

The cohort included 9612 patients in the CARRA Registry from July 2015 to January 2022. They included all patients who had a JIA diagnosis with onset before age 16 and at least one visit with a complete clinical Juvenile Arthritis Disease Activity Score (JADAS) score. Most of the patients (70%) were female, with an average age at enrollment of 11 and a mean time to diagnosis of 10.6 months.

Most of the patients had oligoarthritis (35.5%) or rheumatoid factor–negative polyarthritis (29.4%), followed by enthesitis-related arthritis (10.5%) and then other forms. A total of 4% of patients had a secondary rheumatologic condition. Most of the patients were White (74.9%), with 3.9% Black, 7.6% Hispanic, and 6.5% of more than one race. ADI data were missing for 17.2% of patients.

The researchers assigned a score to each patient that could add up to a maximum of 3. They received 1 point for an annual household income below $50,000, 1 point for having public insurance or no insurance, and 1 point for their guardian having no more than a high school education. Patients with a score of 0 comprised 60.9% of the patients, while 21.3% had a score of 1, 12.9% had a score of 2, and 4.9% had a score of 3.

Just over a quarter of the patients (26.3%) were underinsured, 19.1% were low income, and 16.4% had caregivers with a high school education or less. However, income level was unknown for 24.6% of patients, and guardians’ education level was unknown for 15.7% of patients.

The primary outcomes were the odds of active disease as based on clinical JADAS (at least a 1.1 score for oligoarticular JIA and more than 2.5 for all other subtypes) and odds of functional disability based on the Childhood Health Assessment Questionnaire (CHAQ). Adjustments were made for sex, race/ethnicity, age at enrollment, time to diagnosis, ADI, JIA category, presence of secondary rheumatologic disease, and medication (use of a conventional synthetic disease-modifying antirheumatic drug [DMARD], biologic DMARD, or small molecule drug).

Nearly half (48%) of patients had active disease during follow-up, with an average clinical JADAS score of 4 from the whole cohort. Compared with children with a cumulative disadvantage score of 0, each additional point on the clinical JADAS resulted in significantly increased odds of active disease. Those with the highest score of 3 were twice as likely to have active disease (adjusted odds ratio [aOR], 2.05; P < .001) as those with a score of 0, but those with a score of 1 (aOR, 1.36; P < .001) or 2 (aOR, 1.86; P < .001) were also more likely to have active disease. Other significant independent predictors of active arthritis included being of Black race (aOR, 1.55) or more than one race (aOR, 1.31).

Each of the scored factors also independently increased the likelihood of active disease by similar amounts: 1.69 higher odds for low household income on its own, 1.6 higher odds for public or no insurance, and 1.45 higher odds for high school education or less (all P < .001).

Similarly, odds of functional disability based on CHAQ increased significantly with each additional point. The mean CHAQ score was 0.31, and 46% of patients had functional disability during follow-up. Those with a cumulative social disadvantage score of 3 were three times as likely to have functional disability (aOR, 3.09; P < .001) as those with a score of 0. Those with a score of 1 (aOR, 1.82) or 2 (aOR, 2.81) were also more likely to have functional disability (P < .001). Again, Black individuals (aOR, 2.09) or those of mixed race (aOR, 1.78) had greater odds of functional disability (P < .001).

The independent factor most associated with increased odds of functional disability was a household income below $50,000 a year (OR, 3.03; P < .001), followed by having public or no insurance (OR, 2.57) or a caregiver with no more than a high school education (OR, 1.98). Dr. Soulsby noted that their study was limited by the missing data and may oversimplify the relationships between social determinants of health.

Overall, however, the findings revealed both the importance of social risk screening in the pediatric rheumatology clinic and the coupling of that screening with individual level support for patients, Dr. Soulsby said.

“This study did a great job of harnessing the power of the CARRA Registry,” said Dr. Ardoin, who was not involved in the research. “These findings underscore how important it is for all clinicians, including pediatric rheumatologists, to evaluate every child for social risks of poor outcomes,” she said.

One take-home message from the findings is that once pediatric rheumatologists identify social risks for poor outcomes in their patients, they can “consult with social workers and connect families with community resources in an effort to ameliorate social deprivation.”
 

Childhood Lupus and Reduced Childhood Opportunity

In a similar study looking at children with childhood-onset lupus, researchers similarly identified the way that compounding social determinants of health were linked to greater disease activity.

“We know that structural racism segregates children from historically marginalized groups into different neighborhoods with lower childhood opportunity,” Joyce C. Chang, MD, of Boston Children’s Hospital, told attendees. “When we talk about child opportunity, we’re really describing all of the resources and conditions that helped to promote healthy childhood development,” including factors related to education, physical health, the built environment, and social and economic security, she said.

Dr. Chang and her colleagues therefore assessed the relationship between a 29-indicator Child Opportunity Index for patients with childhood-onset lupus and the severity of their disease presentation and activity over time. They determined the Child Opportunity Index for different neighborhoods and assessed the amount of racial residential segregation around the three institutions involved in the study. Severity of lupus presentation was based on the need for intensive care unit admission or dialysis or a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 10 or higher. Disease activity over time was based on the SLEDAI-2K score.

The patient population included 553 patients with childhood-onset lupus from three institutions: Boston Children’s Hospital, Lurie Children’s Hospital of Chicago, and Children’s of Alabama in Birmingham, Alabama. Across the full population, 30% of the patients were Black and 30% were Hispanic, but the distribution of race and ethnicity varied by institution. Most of the Black patients, for example, were at Children’s of Alabama (59%), while 43% of the Hispanic patients were at Lurie. Across all the sites, 14% of the patients’ families preferred a non-English language as their first language, and just over half the patients (52%) had public insurance.

Dr. Chang did not have data yet from the Lurie and Alabama cohorts, so she presented preliminary data from the Boston Children’s cohort of 148 patients. In those results, children living in neighborhoods of low childhood opportunity had four times higher odds of presenting with severe disease than children living in neighborhoods of very high opportunity. Then the researchers factored in the location quotient that represented the magnitude of racial segregation in a residential area. In areas with high levels of Black vs White segregation, children were 2.5 times more likely to have a more severe initial disease presentation. However, there was not a significant difference in areas highly segregated between Hispanic and non-Hispanic residents.

After initial presentation, the data revealed a dose-dependent relationship between childhood opportunity and severity of disease activity based on SLEDAI-2K. After adjustment for insurance status, race, preferred language, age at disease onset, sex, major organ involvement, initial SLEDAI-2K score at presentation, and follow-up time, disease activity incrementally increased as childhood opportunity decreased (P < .001 for the trend).

The findings suggested that even in regions like Boston, where overall childhood opportunity is higher than the national average, “poor relative neighborhood opportunity is still associated with more severe lupus presentation, as well as higher lupus disease activity during follow-up,” Dr. Chang said. “Area-level conditions may drive inequitable outcomes at numerous points,” including initial access to subspecialty care and after establishing that care, she said.

Dr. Soulsby, Dr. Chang, and Dr. Ardoin reported having no disclosures. Dr. Soulsby’s research was funded by CARRA and the Arthritis Foundation, and Dr. Chang’s research was funded by CARRA.
 

A version of this article appeared on Medscape.com.

The accumulation of multiple adverse social determinants of health is linked to worse disease at initial presentation and worse disease activity over time in children with rheumatologic conditions, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

One study revealed that cumulative factors conferring social disadvantage progressively increased the odds of active disease and functional disability in children with juvenile idiopathic arthritis (JIA). Another study similarly found that children with lupus living in neighborhoods with comparatively fewer resources for childhood opportunity had worse disease at presentation and greater disease activity over follow-up.

The findings suggest that exposure to multiple disadvantaging social variables may be linked to worse outcomes than exposure to any single factor, William Daniel Soulsby, MD, of the University of California San Francisco, told attendees in his presentation of data from the JIA study.

“Most prior studies have analyzed such determinants as independent risk factors,” Dr. Soulsby said. “However, individuals experiencing social disadvantage often face multiple social hardships that rarely act in isolation; studying these factors independently may miss underlying disparities.”

Stacy P. Ardoin, MD, MSc, professor of pediatric and adult rheumatology at Nationwide Children’s Hospital and The Ohio State University in Columbus, and vice president of CARRA, did not find the results of Soulsby’s study surprising, but she said they do “provide important confirmation of our growing understanding of the impact of social determinants of health on the outcomes of children and adolescents with chronic disease like juvenile idiopathic arthritis.” She added: “In medicine, we often think about the bench, the bedside, and the clinic, but this study tells us that if we want to improve outcomes for our patients, we also need to think about the ‘backyard,’ too.”
 

Social Disadvantage With JIA

Dr. Soulsby’s team adopted an approach similar to that of a recent National Survey of Children’s Health analysis that used a combined scoring system to calculate cumulative social disadvantage. The researchers used income level, insurance status, and education level to capture individual factors related to disadvantage and then an area deprivation index (ADI) to capture community factors. While they were unable to use any variables specific to societal factors, they included race, which is relevant at all three levels.

The cohort included 9612 patients in the CARRA Registry from July 2015 to January 2022. They included all patients who had a JIA diagnosis with onset before age 16 and at least one visit with a complete clinical Juvenile Arthritis Disease Activity Score (JADAS) score. Most of the patients (70%) were female, with an average age at enrollment of 11 and a mean time to diagnosis of 10.6 months.

Most of the patients had oligoarthritis (35.5%) or rheumatoid factor–negative polyarthritis (29.4%), followed by enthesitis-related arthritis (10.5%) and then other forms. A total of 4% of patients had a secondary rheumatologic condition. Most of the patients were White (74.9%), with 3.9% Black, 7.6% Hispanic, and 6.5% of more than one race. ADI data were missing for 17.2% of patients.

The researchers assigned a score to each patient that could add up to a maximum of 3. They received 1 point for an annual household income below $50,000, 1 point for having public insurance or no insurance, and 1 point for their guardian having no more than a high school education. Patients with a score of 0 comprised 60.9% of the patients, while 21.3% had a score of 1, 12.9% had a score of 2, and 4.9% had a score of 3.

Just over a quarter of the patients (26.3%) were underinsured, 19.1% were low income, and 16.4% had caregivers with a high school education or less. However, income level was unknown for 24.6% of patients, and guardians’ education level was unknown for 15.7% of patients.

The primary outcomes were the odds of active disease as based on clinical JADAS (at least a 1.1 score for oligoarticular JIA and more than 2.5 for all other subtypes) and odds of functional disability based on the Childhood Health Assessment Questionnaire (CHAQ). Adjustments were made for sex, race/ethnicity, age at enrollment, time to diagnosis, ADI, JIA category, presence of secondary rheumatologic disease, and medication (use of a conventional synthetic disease-modifying antirheumatic drug [DMARD], biologic DMARD, or small molecule drug).

Nearly half (48%) of patients had active disease during follow-up, with an average clinical JADAS score of 4 from the whole cohort. Compared with children with a cumulative disadvantage score of 0, each additional point on the clinical JADAS resulted in significantly increased odds of active disease. Those with the highest score of 3 were twice as likely to have active disease (adjusted odds ratio [aOR], 2.05; P < .001) as those with a score of 0, but those with a score of 1 (aOR, 1.36; P < .001) or 2 (aOR, 1.86; P < .001) were also more likely to have active disease. Other significant independent predictors of active arthritis included being of Black race (aOR, 1.55) or more than one race (aOR, 1.31).

Each of the scored factors also independently increased the likelihood of active disease by similar amounts: 1.69 higher odds for low household income on its own, 1.6 higher odds for public or no insurance, and 1.45 higher odds for high school education or less (all P < .001).

Similarly, odds of functional disability based on CHAQ increased significantly with each additional point. The mean CHAQ score was 0.31, and 46% of patients had functional disability during follow-up. Those with a cumulative social disadvantage score of 3 were three times as likely to have functional disability (aOR, 3.09; P < .001) as those with a score of 0. Those with a score of 1 (aOR, 1.82) or 2 (aOR, 2.81) were also more likely to have functional disability (P < .001). Again, Black individuals (aOR, 2.09) or those of mixed race (aOR, 1.78) had greater odds of functional disability (P < .001).

The independent factor most associated with increased odds of functional disability was a household income below $50,000 a year (OR, 3.03; P < .001), followed by having public or no insurance (OR, 2.57) or a caregiver with no more than a high school education (OR, 1.98). Dr. Soulsby noted that their study was limited by the missing data and may oversimplify the relationships between social determinants of health.

Overall, however, the findings revealed both the importance of social risk screening in the pediatric rheumatology clinic and the coupling of that screening with individual level support for patients, Dr. Soulsby said.

“This study did a great job of harnessing the power of the CARRA Registry,” said Dr. Ardoin, who was not involved in the research. “These findings underscore how important it is for all clinicians, including pediatric rheumatologists, to evaluate every child for social risks of poor outcomes,” she said.

One take-home message from the findings is that once pediatric rheumatologists identify social risks for poor outcomes in their patients, they can “consult with social workers and connect families with community resources in an effort to ameliorate social deprivation.”
 

Childhood Lupus and Reduced Childhood Opportunity

In a similar study looking at children with childhood-onset lupus, researchers similarly identified the way that compounding social determinants of health were linked to greater disease activity.

“We know that structural racism segregates children from historically marginalized groups into different neighborhoods with lower childhood opportunity,” Joyce C. Chang, MD, of Boston Children’s Hospital, told attendees. “When we talk about child opportunity, we’re really describing all of the resources and conditions that helped to promote healthy childhood development,” including factors related to education, physical health, the built environment, and social and economic security, she said.

Dr. Chang and her colleagues therefore assessed the relationship between a 29-indicator Child Opportunity Index for patients with childhood-onset lupus and the severity of their disease presentation and activity over time. They determined the Child Opportunity Index for different neighborhoods and assessed the amount of racial residential segregation around the three institutions involved in the study. Severity of lupus presentation was based on the need for intensive care unit admission or dialysis or a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 10 or higher. Disease activity over time was based on the SLEDAI-2K score.

The patient population included 553 patients with childhood-onset lupus from three institutions: Boston Children’s Hospital, Lurie Children’s Hospital of Chicago, and Children’s of Alabama in Birmingham, Alabama. Across the full population, 30% of the patients were Black and 30% were Hispanic, but the distribution of race and ethnicity varied by institution. Most of the Black patients, for example, were at Children’s of Alabama (59%), while 43% of the Hispanic patients were at Lurie. Across all the sites, 14% of the patients’ families preferred a non-English language as their first language, and just over half the patients (52%) had public insurance.

Dr. Chang did not have data yet from the Lurie and Alabama cohorts, so she presented preliminary data from the Boston Children’s cohort of 148 patients. In those results, children living in neighborhoods of low childhood opportunity had four times higher odds of presenting with severe disease than children living in neighborhoods of very high opportunity. Then the researchers factored in the location quotient that represented the magnitude of racial segregation in a residential area. In areas with high levels of Black vs White segregation, children were 2.5 times more likely to have a more severe initial disease presentation. However, there was not a significant difference in areas highly segregated between Hispanic and non-Hispanic residents.

After initial presentation, the data revealed a dose-dependent relationship between childhood opportunity and severity of disease activity based on SLEDAI-2K. After adjustment for insurance status, race, preferred language, age at disease onset, sex, major organ involvement, initial SLEDAI-2K score at presentation, and follow-up time, disease activity incrementally increased as childhood opportunity decreased (P < .001 for the trend).

The findings suggested that even in regions like Boston, where overall childhood opportunity is higher than the national average, “poor relative neighborhood opportunity is still associated with more severe lupus presentation, as well as higher lupus disease activity during follow-up,” Dr. Chang said. “Area-level conditions may drive inequitable outcomes at numerous points,” including initial access to subspecialty care and after establishing that care, she said.

Dr. Soulsby, Dr. Chang, and Dr. Ardoin reported having no disclosures. Dr. Soulsby’s research was funded by CARRA and the Arthritis Foundation, and Dr. Chang’s research was funded by CARRA.
 

A version of this article appeared on Medscape.com.

The accumulation of multiple adverse social determinants of health is linked to worse disease at initial presentation and worse disease activity over time in children with rheumatologic conditions, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

One study revealed that cumulative factors conferring social disadvantage progressively increased the odds of active disease and functional disability in children with juvenile idiopathic arthritis (JIA). Another study similarly found that children with lupus living in neighborhoods with comparatively fewer resources for childhood opportunity had worse disease at presentation and greater disease activity over follow-up.

The findings suggest that exposure to multiple disadvantaging social variables may be linked to worse outcomes than exposure to any single factor, William Daniel Soulsby, MD, of the University of California San Francisco, told attendees in his presentation of data from the JIA study.

“Most prior studies have analyzed such determinants as independent risk factors,” Dr. Soulsby said. “However, individuals experiencing social disadvantage often face multiple social hardships that rarely act in isolation; studying these factors independently may miss underlying disparities.”

Stacy P. Ardoin, MD, MSc, professor of pediatric and adult rheumatology at Nationwide Children’s Hospital and The Ohio State University in Columbus, and vice president of CARRA, did not find the results of Soulsby’s study surprising, but she said they do “provide important confirmation of our growing understanding of the impact of social determinants of health on the outcomes of children and adolescents with chronic disease like juvenile idiopathic arthritis.” She added: “In medicine, we often think about the bench, the bedside, and the clinic, but this study tells us that if we want to improve outcomes for our patients, we also need to think about the ‘backyard,’ too.”
 

Social Disadvantage With JIA

Dr. Soulsby’s team adopted an approach similar to that of a recent National Survey of Children’s Health analysis that used a combined scoring system to calculate cumulative social disadvantage. The researchers used income level, insurance status, and education level to capture individual factors related to disadvantage and then an area deprivation index (ADI) to capture community factors. While they were unable to use any variables specific to societal factors, they included race, which is relevant at all three levels.

The cohort included 9612 patients in the CARRA Registry from July 2015 to January 2022. They included all patients who had a JIA diagnosis with onset before age 16 and at least one visit with a complete clinical Juvenile Arthritis Disease Activity Score (JADAS) score. Most of the patients (70%) were female, with an average age at enrollment of 11 and a mean time to diagnosis of 10.6 months.

Most of the patients had oligoarthritis (35.5%) or rheumatoid factor–negative polyarthritis (29.4%), followed by enthesitis-related arthritis (10.5%) and then other forms. A total of 4% of patients had a secondary rheumatologic condition. Most of the patients were White (74.9%), with 3.9% Black, 7.6% Hispanic, and 6.5% of more than one race. ADI data were missing for 17.2% of patients.

The researchers assigned a score to each patient that could add up to a maximum of 3. They received 1 point for an annual household income below $50,000, 1 point for having public insurance or no insurance, and 1 point for their guardian having no more than a high school education. Patients with a score of 0 comprised 60.9% of the patients, while 21.3% had a score of 1, 12.9% had a score of 2, and 4.9% had a score of 3.

Just over a quarter of the patients (26.3%) were underinsured, 19.1% were low income, and 16.4% had caregivers with a high school education or less. However, income level was unknown for 24.6% of patients, and guardians’ education level was unknown for 15.7% of patients.

The primary outcomes were the odds of active disease as based on clinical JADAS (at least a 1.1 score for oligoarticular JIA and more than 2.5 for all other subtypes) and odds of functional disability based on the Childhood Health Assessment Questionnaire (CHAQ). Adjustments were made for sex, race/ethnicity, age at enrollment, time to diagnosis, ADI, JIA category, presence of secondary rheumatologic disease, and medication (use of a conventional synthetic disease-modifying antirheumatic drug [DMARD], biologic DMARD, or small molecule drug).

Nearly half (48%) of patients had active disease during follow-up, with an average clinical JADAS score of 4 from the whole cohort. Compared with children with a cumulative disadvantage score of 0, each additional point on the clinical JADAS resulted in significantly increased odds of active disease. Those with the highest score of 3 were twice as likely to have active disease (adjusted odds ratio [aOR], 2.05; P < .001) as those with a score of 0, but those with a score of 1 (aOR, 1.36; P < .001) or 2 (aOR, 1.86; P < .001) were also more likely to have active disease. Other significant independent predictors of active arthritis included being of Black race (aOR, 1.55) or more than one race (aOR, 1.31).

Each of the scored factors also independently increased the likelihood of active disease by similar amounts: 1.69 higher odds for low household income on its own, 1.6 higher odds for public or no insurance, and 1.45 higher odds for high school education or less (all P < .001).

Similarly, odds of functional disability based on CHAQ increased significantly with each additional point. The mean CHAQ score was 0.31, and 46% of patients had functional disability during follow-up. Those with a cumulative social disadvantage score of 3 were three times as likely to have functional disability (aOR, 3.09; P < .001) as those with a score of 0. Those with a score of 1 (aOR, 1.82) or 2 (aOR, 2.81) were also more likely to have functional disability (P < .001). Again, Black individuals (aOR, 2.09) or those of mixed race (aOR, 1.78) had greater odds of functional disability (P < .001).

The independent factor most associated with increased odds of functional disability was a household income below $50,000 a year (OR, 3.03; P < .001), followed by having public or no insurance (OR, 2.57) or a caregiver with no more than a high school education (OR, 1.98). Dr. Soulsby noted that their study was limited by the missing data and may oversimplify the relationships between social determinants of health.

Overall, however, the findings revealed both the importance of social risk screening in the pediatric rheumatology clinic and the coupling of that screening with individual level support for patients, Dr. Soulsby said.

“This study did a great job of harnessing the power of the CARRA Registry,” said Dr. Ardoin, who was not involved in the research. “These findings underscore how important it is for all clinicians, including pediatric rheumatologists, to evaluate every child for social risks of poor outcomes,” she said.

One take-home message from the findings is that once pediatric rheumatologists identify social risks for poor outcomes in their patients, they can “consult with social workers and connect families with community resources in an effort to ameliorate social deprivation.”
 

Childhood Lupus and Reduced Childhood Opportunity

In a similar study looking at children with childhood-onset lupus, researchers similarly identified the way that compounding social determinants of health were linked to greater disease activity.

“We know that structural racism segregates children from historically marginalized groups into different neighborhoods with lower childhood opportunity,” Joyce C. Chang, MD, of Boston Children’s Hospital, told attendees. “When we talk about child opportunity, we’re really describing all of the resources and conditions that helped to promote healthy childhood development,” including factors related to education, physical health, the built environment, and social and economic security, she said.

Dr. Chang and her colleagues therefore assessed the relationship between a 29-indicator Child Opportunity Index for patients with childhood-onset lupus and the severity of their disease presentation and activity over time. They determined the Child Opportunity Index for different neighborhoods and assessed the amount of racial residential segregation around the three institutions involved in the study. Severity of lupus presentation was based on the need for intensive care unit admission or dialysis or a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 10 or higher. Disease activity over time was based on the SLEDAI-2K score.

The patient population included 553 patients with childhood-onset lupus from three institutions: Boston Children’s Hospital, Lurie Children’s Hospital of Chicago, and Children’s of Alabama in Birmingham, Alabama. Across the full population, 30% of the patients were Black and 30% were Hispanic, but the distribution of race and ethnicity varied by institution. Most of the Black patients, for example, were at Children’s of Alabama (59%), while 43% of the Hispanic patients were at Lurie. Across all the sites, 14% of the patients’ families preferred a non-English language as their first language, and just over half the patients (52%) had public insurance.

Dr. Chang did not have data yet from the Lurie and Alabama cohorts, so she presented preliminary data from the Boston Children’s cohort of 148 patients. In those results, children living in neighborhoods of low childhood opportunity had four times higher odds of presenting with severe disease than children living in neighborhoods of very high opportunity. Then the researchers factored in the location quotient that represented the magnitude of racial segregation in a residential area. In areas with high levels of Black vs White segregation, children were 2.5 times more likely to have a more severe initial disease presentation. However, there was not a significant difference in areas highly segregated between Hispanic and non-Hispanic residents.

After initial presentation, the data revealed a dose-dependent relationship between childhood opportunity and severity of disease activity based on SLEDAI-2K. After adjustment for insurance status, race, preferred language, age at disease onset, sex, major organ involvement, initial SLEDAI-2K score at presentation, and follow-up time, disease activity incrementally increased as childhood opportunity decreased (P < .001 for the trend).

The findings suggested that even in regions like Boston, where overall childhood opportunity is higher than the national average, “poor relative neighborhood opportunity is still associated with more severe lupus presentation, as well as higher lupus disease activity during follow-up,” Dr. Chang said. “Area-level conditions may drive inequitable outcomes at numerous points,” including initial access to subspecialty care and after establishing that care, she said.

Dr. Soulsby, Dr. Chang, and Dr. Ardoin reported having no disclosures. Dr. Soulsby’s research was funded by CARRA and the Arthritis Foundation, and Dr. Chang’s research was funded by CARRA.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Anti-osteoporosis medications reduce fracture risk similarly, regardless of whether patients are younger or older than 70 years.

METHODOLOGY:

• Investigators conducted the study as part of a  to assess bone mineral density as a surrogate marker for fracture risk.
• Analyses used individual patient data from 23 randomized placebo-controlled trials of anti-osteoporosis medications (11 of bisphosphonates, four of selective estrogen receptor modulators, three of anabolic medications, two of hormone replacement therapy, and one each of odanacatib, denosumab, and romosozumab).
• Overall, 43% of the included 123,164 patients were aged 70 years or older.
• The main outcomes were fractures and bone mineral density.

TAKEAWAY:

• There was a similar benefit regardless of age when it came to the reduction in risks for hip fracture (odds ratio, 0.65 vs 0.72; P for interaction = .50) and any fracture (odds ratio, 0.72 vs 0.70; P for interaction = .20).
• Findings were comparable in analyses restricted to bisphosphonate trials, except that the reduction in hip fracture risk was greater among the younger group (hazard ratio, 0.44 vs 0.79; P for interaction = .02).
• The benefit of anti-osteoporosis medication in increasing hip and spine bone mineral density at 24 months was significantly greater among the older patients.

IN PRACTICE:

Taken together, the study results “strongly support treatment in those over age 70,” the authors wrote. “These are important findings with potential impact in patient treatment since it goes against a common misconception that medications are less effective in older people,” they added.

SOURCE:

The study was led by Marian Schini, MD, PhD, FHEA, University of Sheffield, England, and was published online in the Journal of Bone and Mineral Research.

LIMITATIONS:

Limitations included a preponderance of female patients (99%), possible residual confounding, a lack of analysis of adverse effects, and potentially different findings using alternate age cutoffs.

DISCLOSURES:

The study was funded by the American Society for Bone Mineral Research. Some authors disclosed affiliations with companies that manufacture anti-osteoporosis drugs.

A version of this article appeared on Medscape.com.

TOPLINE:

Anti-osteoporosis medications reduce fracture risk similarly, regardless of whether patients are younger or older than 70 years.

METHODOLOGY:

• Investigators conducted the study as part of a  to assess bone mineral density as a surrogate marker for fracture risk.
• Analyses used individual patient data from 23 randomized placebo-controlled trials of anti-osteoporosis medications (11 of bisphosphonates, four of selective estrogen receptor modulators, three of anabolic medications, two of hormone replacement therapy, and one each of odanacatib, denosumab, and romosozumab).
• Overall, 43% of the included 123,164 patients were aged 70 years or older.
• The main outcomes were fractures and bone mineral density.

TAKEAWAY:

• There was a similar benefit regardless of age when it came to the reduction in risks for hip fracture (odds ratio, 0.65 vs 0.72; P for interaction = .50) and any fracture (odds ratio, 0.72 vs 0.70; P for interaction = .20).
• Findings were comparable in analyses restricted to bisphosphonate trials, except that the reduction in hip fracture risk was greater among the younger group (hazard ratio, 0.44 vs 0.79; P for interaction = .02).
• The benefit of anti-osteoporosis medication in increasing hip and spine bone mineral density at 24 months was significantly greater among the older patients.

IN PRACTICE:

Taken together, the study results “strongly support treatment in those over age 70,” the authors wrote. “These are important findings with potential impact in patient treatment since it goes against a common misconception that medications are less effective in older people,” they added.

SOURCE:

The study was led by Marian Schini, MD, PhD, FHEA, University of Sheffield, England, and was published online in the Journal of Bone and Mineral Research.

LIMITATIONS:

Limitations included a preponderance of female patients (99%), possible residual confounding, a lack of analysis of adverse effects, and potentially different findings using alternate age cutoffs.

DISCLOSURES:

The study was funded by the American Society for Bone Mineral Research. Some authors disclosed affiliations with companies that manufacture anti-osteoporosis drugs.

A version of this article appeared on Medscape.com.

TOPLINE:

Anti-osteoporosis medications reduce fracture risk similarly, regardless of whether patients are younger or older than 70 years.

METHODOLOGY:

• Investigators conducted the study as part of a  to assess bone mineral density as a surrogate marker for fracture risk.
• Analyses used individual patient data from 23 randomized placebo-controlled trials of anti-osteoporosis medications (11 of bisphosphonates, four of selective estrogen receptor modulators, three of anabolic medications, two of hormone replacement therapy, and one each of odanacatib, denosumab, and romosozumab).
• Overall, 43% of the included 123,164 patients were aged 70 years or older.
• The main outcomes were fractures and bone mineral density.

TAKEAWAY:

• There was a similar benefit regardless of age when it came to the reduction in risks for hip fracture (odds ratio, 0.65 vs 0.72; P for interaction = .50) and any fracture (odds ratio, 0.72 vs 0.70; P for interaction = .20).
• Findings were comparable in analyses restricted to bisphosphonate trials, except that the reduction in hip fracture risk was greater among the younger group (hazard ratio, 0.44 vs 0.79; P for interaction = .02).
• The benefit of anti-osteoporosis medication in increasing hip and spine bone mineral density at 24 months was significantly greater among the older patients.

IN PRACTICE:

Taken together, the study results “strongly support treatment in those over age 70,” the authors wrote. “These are important findings with potential impact in patient treatment since it goes against a common misconception that medications are less effective in older people,” they added.

SOURCE:

The study was led by Marian Schini, MD, PhD, FHEA, University of Sheffield, England, and was published online in the Journal of Bone and Mineral Research.

LIMITATIONS:

Limitations included a preponderance of female patients (99%), possible residual confounding, a lack of analysis of adverse effects, and potentially different findings using alternate age cutoffs.

DISCLOSURES:

The study was funded by the American Society for Bone Mineral Research. Some authors disclosed affiliations with companies that manufacture anti-osteoporosis drugs.

A version of this article appeared on Medscape.com.