Psoriatic Arthritis

Key clinical point: The risk for uveitis was increased by more than double in patients with psoriatic arthritis (PsA), with past uveitis events and etanercept treatment being significant risk factors.

Major finding: The risk for uveitis was higher in patients with PsA vs matched control individuals without PsA (adjusted hazard ratio 2.38; 95% CI 1.80-3.15). Among patients with PsA, past events of uveitis (adjusted odds ratio [aOR] 136.4; 95% CI 27.38-679.88) and treatment with etanercept (aOR 2.57; 95% CI 1.45-4.57) were associated with an increased risk for uveitis.

Study details: This retrospective matched cohort study included 6147 patients with newly diagnosed PsA and 23,999 matched control individuals without PsA.

Disclosures: This study did not disclose the funding source. The authors declared no conflicts of interest.

Source: Hijazi N et al. The risk factors for uveitis among psoriatic arthritis patients: A population-based cohort study. Clin Rheumatol. 2023 (Dec 11). doi: 10.1007/s10067-023-06834-y

Key clinical point: The risk for uveitis was increased by more than double in patients with psoriatic arthritis (PsA), with past uveitis events and etanercept treatment being significant risk factors.

Major finding: The risk for uveitis was higher in patients with PsA vs matched control individuals without PsA (adjusted hazard ratio 2.38; 95% CI 1.80-3.15). Among patients with PsA, past events of uveitis (adjusted odds ratio [aOR] 136.4; 95% CI 27.38-679.88) and treatment with etanercept (aOR 2.57; 95% CI 1.45-4.57) were associated with an increased risk for uveitis.

Study details: This retrospective matched cohort study included 6147 patients with newly diagnosed PsA and 23,999 matched control individuals without PsA.

Disclosures: This study did not disclose the funding source. The authors declared no conflicts of interest.

Source: Hijazi N et al. The risk factors for uveitis among psoriatic arthritis patients: A population-based cohort study. Clin Rheumatol. 2023 (Dec 11). doi: 10.1007/s10067-023-06834-y

Key clinical point: The risk for uveitis was increased by more than double in patients with psoriatic arthritis (PsA), with past uveitis events and etanercept treatment being significant risk factors.

Major finding: The risk for uveitis was higher in patients with PsA vs matched control individuals without PsA (adjusted hazard ratio 2.38; 95% CI 1.80-3.15). Among patients with PsA, past events of uveitis (adjusted odds ratio [aOR] 136.4; 95% CI 27.38-679.88) and treatment with etanercept (aOR 2.57; 95% CI 1.45-4.57) were associated with an increased risk for uveitis.

Study details: This retrospective matched cohort study included 6147 patients with newly diagnosed PsA and 23,999 matched control individuals without PsA.

Disclosures: This study did not disclose the funding source. The authors declared no conflicts of interest.

Source: Hijazi N et al. The risk factors for uveitis among psoriatic arthritis patients: A population-based cohort study. Clin Rheumatol. 2023 (Dec 11). doi: 10.1007/s10067-023-06834-y

Key clinical point: Functional training (FT) and resistance exercise (RE) improved functional capacity, functional status, disease activity, and muscle strength to a comparable extent in patients with psoriatic arthritis (PsA).

Major finding: FT and RE led to similar improvements in functional capacity measured by the Bath Ankylosing Spondylitis Functional Index (P = .919), functional status measured by the Health Assessment Questionnaire for the Spondyloarthropathies (P = 0.932), disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = .700), and muscle strength in patients with PsA. No adverse event occurred in either group.

Study details: Findings are from a 12-week, single-blind trial that included 41 patients with PsA who were randomly assigned to undergo FT with elastic bands or RE with weight machines.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Silva DR et al. Effectiveness of functional training versus resistance exercise in patients with psoriatic arthritis: Randomized controlled trial. Adv Rheumatol. 2023;63:58. (Dec 13). doi: 10.1186/s42358-023-00342-y

Key clinical point: Functional training (FT) and resistance exercise (RE) improved functional capacity, functional status, disease activity, and muscle strength to a comparable extent in patients with psoriatic arthritis (PsA).

Major finding: FT and RE led to similar improvements in functional capacity measured by the Bath Ankylosing Spondylitis Functional Index (P = .919), functional status measured by the Health Assessment Questionnaire for the Spondyloarthropathies (P = 0.932), disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = .700), and muscle strength in patients with PsA. No adverse event occurred in either group.

Study details: Findings are from a 12-week, single-blind trial that included 41 patients with PsA who were randomly assigned to undergo FT with elastic bands or RE with weight machines.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Silva DR et al. Effectiveness of functional training versus resistance exercise in patients with psoriatic arthritis: Randomized controlled trial. Adv Rheumatol. 2023;63:58. (Dec 13). doi: 10.1186/s42358-023-00342-y

Key clinical point: Functional training (FT) and resistance exercise (RE) improved functional capacity, functional status, disease activity, and muscle strength to a comparable extent in patients with psoriatic arthritis (PsA).

Major finding: FT and RE led to similar improvements in functional capacity measured by the Bath Ankylosing Spondylitis Functional Index (P = .919), functional status measured by the Health Assessment Questionnaire for the Spondyloarthropathies (P = 0.932), disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = .700), and muscle strength in patients with PsA. No adverse event occurred in either group.

Study details: Findings are from a 12-week, single-blind trial that included 41 patients with PsA who were randomly assigned to undergo FT with elastic bands or RE with weight machines.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Silva DR et al. Effectiveness of functional training versus resistance exercise in patients with psoriatic arthritis: Randomized controlled trial. Adv Rheumatol. 2023;63:58. (Dec 13). doi: 10.1186/s42358-023-00342-y

Key clinical point: Adults with pre-existing psoriatic arthritis (PsA) who underwent surgery for lumbar degenerative disease (LDD) faced increased odds of unfavorable discharge and venous thromboembolism (VTE) events compared with those without PsA.

Major finding: A diagnosis of PsA in patients who underwent LDD surgery increased the odds of unfavorable discharge by 26% (adjusted odds ratio [aOR] 1.26; 95% CI 1.03-1.55) and nearly doubled the risk for VTE (aOR 1.99; 95% CI 1.05-3.75).

Study details: This population-based retrospective study included 467,814 patients (age ≥ 20 years) who underwent surgery for LDD, of whom 883 patients had pre-existing PsA and were matched to 8830 patients without PsA.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Chen MY et al. Psoriatic arthritis increases the risk of venous thromboembolism following degenerative lumbar spine surgery: An analysis of U.S. Nationwide Inpatient Sample 2005–2018. Heliyon. 2023;10(1):E23613 (Dec 12). doi: 10.1016/j.heliyon.2023.e23613

Key clinical point: Adults with pre-existing psoriatic arthritis (PsA) who underwent surgery for lumbar degenerative disease (LDD) faced increased odds of unfavorable discharge and venous thromboembolism (VTE) events compared with those without PsA.

Major finding: A diagnosis of PsA in patients who underwent LDD surgery increased the odds of unfavorable discharge by 26% (adjusted odds ratio [aOR] 1.26; 95% CI 1.03-1.55) and nearly doubled the risk for VTE (aOR 1.99; 95% CI 1.05-3.75).

Study details: This population-based retrospective study included 467,814 patients (age ≥ 20 years) who underwent surgery for LDD, of whom 883 patients had pre-existing PsA and were matched to 8830 patients without PsA.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Chen MY et al. Psoriatic arthritis increases the risk of venous thromboembolism following degenerative lumbar spine surgery: An analysis of U.S. Nationwide Inpatient Sample 2005–2018. Heliyon. 2023;10(1):E23613 (Dec 12). doi: 10.1016/j.heliyon.2023.e23613

Key clinical point: Adults with pre-existing psoriatic arthritis (PsA) who underwent surgery for lumbar degenerative disease (LDD) faced increased odds of unfavorable discharge and venous thromboembolism (VTE) events compared with those without PsA.

Major finding: A diagnosis of PsA in patients who underwent LDD surgery increased the odds of unfavorable discharge by 26% (adjusted odds ratio [aOR] 1.26; 95% CI 1.03-1.55) and nearly doubled the risk for VTE (aOR 1.99; 95% CI 1.05-3.75).

Study details: This population-based retrospective study included 467,814 patients (age ≥ 20 years) who underwent surgery for LDD, of whom 883 patients had pre-existing PsA and were matched to 8830 patients without PsA.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Chen MY et al. Psoriatic arthritis increases the risk of venous thromboembolism following degenerative lumbar spine surgery: An analysis of U.S. Nationwide Inpatient Sample 2005–2018. Heliyon. 2023;10(1):E23613 (Dec 12). doi: 10.1016/j.heliyon.2023.e23613

Key clinical point: Female patients with psoriatic arthritis (PsA) who received tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) showed lower treatment persistence than male patients with PsA who received the same therapeutic class of drugs.

Major finding: Women demonstrated 20%-40% lower treatment persistence rates than men for TNFi (adjusted hazard ratio [aHR] 1.4; 99% CI 1.3-1.5) and IL-17i (aHR 1.2; 99% CI 1.1-1.3) therapies; however, the treatment persistence between both sexes was comparable for IL12/23i (aHR 1.1; 99% CI 0.9-1.3), IL23i (aHR 1.1; 99% CI 0.7-1.5), and Janus kinase inhibitor (aHR 1.2; 99% CI 0.9-1.6) therapies.

Study details: This nationwide cohort study included 14,778 patients with PsA who were new users of targeted therapies, of whom 57% were women and 43% were men.

Disclosures: This study did not receive any specific grant. Two authors declared receiving subsidy or consulting fees from or being an investigator for various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Pina Vegas L et al. Influence of sex on the persistence of different classes of targeted therapies for psoriatic arthritis: A cohort study of 14 778 patients from the French health insurance database (SNDS). RMD Open. 2023;9:e003570 (Dec 19). doi: 10.1136/rmdopen-2023-003570

Key clinical point: Female patients with psoriatic arthritis (PsA) who received tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) showed lower treatment persistence than male patients with PsA who received the same therapeutic class of drugs.

Major finding: Women demonstrated 20%-40% lower treatment persistence rates than men for TNFi (adjusted hazard ratio [aHR] 1.4; 99% CI 1.3-1.5) and IL-17i (aHR 1.2; 99% CI 1.1-1.3) therapies; however, the treatment persistence between both sexes was comparable for IL12/23i (aHR 1.1; 99% CI 0.9-1.3), IL23i (aHR 1.1; 99% CI 0.7-1.5), and Janus kinase inhibitor (aHR 1.2; 99% CI 0.9-1.6) therapies.

Study details: This nationwide cohort study included 14,778 patients with PsA who were new users of targeted therapies, of whom 57% were women and 43% were men.

Disclosures: This study did not receive any specific grant. Two authors declared receiving subsidy or consulting fees from or being an investigator for various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Pina Vegas L et al. Influence of sex on the persistence of different classes of targeted therapies for psoriatic arthritis: A cohort study of 14 778 patients from the French health insurance database (SNDS). RMD Open. 2023;9:e003570 (Dec 19). doi: 10.1136/rmdopen-2023-003570

Key clinical point: Female patients with psoriatic arthritis (PsA) who received tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) showed lower treatment persistence than male patients with PsA who received the same therapeutic class of drugs.

Major finding: Women demonstrated 20%-40% lower treatment persistence rates than men for TNFi (adjusted hazard ratio [aHR] 1.4; 99% CI 1.3-1.5) and IL-17i (aHR 1.2; 99% CI 1.1-1.3) therapies; however, the treatment persistence between both sexes was comparable for IL12/23i (aHR 1.1; 99% CI 0.9-1.3), IL23i (aHR 1.1; 99% CI 0.7-1.5), and Janus kinase inhibitor (aHR 1.2; 99% CI 0.9-1.6) therapies.

Study details: This nationwide cohort study included 14,778 patients with PsA who were new users of targeted therapies, of whom 57% were women and 43% were men.

Disclosures: This study did not receive any specific grant. Two authors declared receiving subsidy or consulting fees from or being an investigator for various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Pina Vegas L et al. Influence of sex on the persistence of different classes of targeted therapies for psoriatic arthritis: A cohort study of 14 778 patients from the French health insurance database (SNDS). RMD Open. 2023;9:e003570 (Dec 19). doi: 10.1136/rmdopen-2023-003570

Key clinical point: Although Psoriatic Arthritis Impact of Disease questionnaire-12 items (PsAID-12) scores were higher in patients with psoriatic arthritis (PsA) who did vs did not have a treatment escalation, physicians relied more on their assessment of disease activity while making treatment-related decisions.

Major finding: Higher mean PsAID-12 score correlated with higher odds of treatment escalation in patients with PsA (odds ratio [OR] 1.58; P < .0001), whereas physician’s assessment of disease activity had the most significant impact on likelihood of treatment escalation (OR 2.68; P < .0001). Longer disease duration, treatment with nonbiologics, and a higher swollen joint count also increased the odds for treatment escalation.

Study details: Findings are from a cross-sectional analysis (the ASSIST study) that included 503 patients with PsA (age ≥ 18 years), of whom 160 patients underwent treatment escalation.

Disclosures: This study was funded by Amgen, and the National Institute for Health Research Oxford Biomedical Research Centre. Several authors declared receiving grants, honoraria, consultancy fees, or travel support from or having ties with various sources, including Amgen.

Source: Coyle C et al. How do patient reported outcome measures affect treatment intensification and patient satisfaction in the management of psoriatic arthritis? A cross sectional study of 503 patients. Rheumatology (Oxford). 2024 (Jan 8). doi: 10.1093/rheumatology/kead679

Key clinical point: Although Psoriatic Arthritis Impact of Disease questionnaire-12 items (PsAID-12) scores were higher in patients with psoriatic arthritis (PsA) who did vs did not have a treatment escalation, physicians relied more on their assessment of disease activity while making treatment-related decisions.

Major finding: Higher mean PsAID-12 score correlated with higher odds of treatment escalation in patients with PsA (odds ratio [OR] 1.58; P < .0001), whereas physician’s assessment of disease activity had the most significant impact on likelihood of treatment escalation (OR 2.68; P < .0001). Longer disease duration, treatment with nonbiologics, and a higher swollen joint count also increased the odds for treatment escalation.

Study details: Findings are from a cross-sectional analysis (the ASSIST study) that included 503 patients with PsA (age ≥ 18 years), of whom 160 patients underwent treatment escalation.

Disclosures: This study was funded by Amgen, and the National Institute for Health Research Oxford Biomedical Research Centre. Several authors declared receiving grants, honoraria, consultancy fees, or travel support from or having ties with various sources, including Amgen.

Source: Coyle C et al. How do patient reported outcome measures affect treatment intensification and patient satisfaction in the management of psoriatic arthritis? A cross sectional study of 503 patients. Rheumatology (Oxford). 2024 (Jan 8). doi: 10.1093/rheumatology/kead679

Key clinical point: Although Psoriatic Arthritis Impact of Disease questionnaire-12 items (PsAID-12) scores were higher in patients with psoriatic arthritis (PsA) who did vs did not have a treatment escalation, physicians relied more on their assessment of disease activity while making treatment-related decisions.

Major finding: Higher mean PsAID-12 score correlated with higher odds of treatment escalation in patients with PsA (odds ratio [OR] 1.58; P < .0001), whereas physician’s assessment of disease activity had the most significant impact on likelihood of treatment escalation (OR 2.68; P < .0001). Longer disease duration, treatment with nonbiologics, and a higher swollen joint count also increased the odds for treatment escalation.

Study details: Findings are from a cross-sectional analysis (the ASSIST study) that included 503 patients with PsA (age ≥ 18 years), of whom 160 patients underwent treatment escalation.

Disclosures: This study was funded by Amgen, and the National Institute for Health Research Oxford Biomedical Research Centre. Several authors declared receiving grants, honoraria, consultancy fees, or travel support from or having ties with various sources, including Amgen.

Source: Coyle C et al. How do patient reported outcome measures affect treatment intensification and patient satisfaction in the management of psoriatic arthritis? A cross sectional study of 503 patients. Rheumatology (Oxford). 2024 (Jan 8). doi: 10.1093/rheumatology/kead679

TOPLINE:

Exercise with weight machines or elastic resistance bands yielded similar improvements in strength and function in adults with psoriatic arthritis (PsA) after 12 weeks.

METHODOLOGY:

• Researchers recruited 41 adults aged 18-65 years with PsA who were then randomized to a functional training group (FT) or a resistance exercise group (RE) for 12 weeks of twice-weekly, 55-minute sessions under the supervision of a physical trainer.
• Functional training involved the use of elastic bands to work upper body, lower body, and trunk muscles including the biceps, triceps, back quadriceps, glutes, and hips; the RE used weight machines instead of bands.
• Participants were evaluated at baseline and after 6 and 12 weeks of training sessions; the primary outcome was functional status based on the Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S).
• Secondary outcomes included the Bath Ankylosing Spondylitis Functional Index (BASFI) to assess functional capacity, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Disease Activity Score in 28 joints (DAS28) to assess disease activity, and the Short Form 36 (SF-36) to measure quality of life.

TAKEAWAY:

• Participants in both groups showed significant improvement from baseline on the primary outcome measure, with no significant differences between the groups on the primary outcome of function or secondary measures of function and disease activity after 12 weeks.
• Significant intragroup changes occurred between times for both groups on the HAQ-S, BASFI, BASDAI, and DAS28 (P = .001, .007, .001, and .001, respectively).
• Improvement in quality of life was significant from baseline and similar between the FT and RE, with the exception of the “social aspects” domain, for which only the FT showed significant improvement.
• No intervention-related adverse events were reported in either group.

IN PRACTICE:

Despite the absence of consensus guidelines on the use and effectiveness of FT and RE, “we can conclude that both FT and RE have similar effectiveness in improving functional capacity, functional status, disease activity, general quality of life, and muscle strength in patients with psoriatic arthritis,” the researchers wrote.

SOURCE:

The study was led by Diego Roger Silva, MD, of the Universidade Federal de São Paulo, Brazil, and published online in Advances in Rheumatology.

LIMITATIONS:

The study population was recruited from outpatient clinics, and the mean age of 52 years was higher than in previous studies; the study also lacked long-term follow-up data.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Exercise with weight machines or elastic resistance bands yielded similar improvements in strength and function in adults with psoriatic arthritis (PsA) after 12 weeks.

METHODOLOGY:

• Researchers recruited 41 adults aged 18-65 years with PsA who were then randomized to a functional training group (FT) or a resistance exercise group (RE) for 12 weeks of twice-weekly, 55-minute sessions under the supervision of a physical trainer.
• Functional training involved the use of elastic bands to work upper body, lower body, and trunk muscles including the biceps, triceps, back quadriceps, glutes, and hips; the RE used weight machines instead of bands.
• Participants were evaluated at baseline and after 6 and 12 weeks of training sessions; the primary outcome was functional status based on the Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S).
• Secondary outcomes included the Bath Ankylosing Spondylitis Functional Index (BASFI) to assess functional capacity, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Disease Activity Score in 28 joints (DAS28) to assess disease activity, and the Short Form 36 (SF-36) to measure quality of life.

TAKEAWAY:

• Participants in both groups showed significant improvement from baseline on the primary outcome measure, with no significant differences between the groups on the primary outcome of function or secondary measures of function and disease activity after 12 weeks.
• Significant intragroup changes occurred between times for both groups on the HAQ-S, BASFI, BASDAI, and DAS28 (P = .001, .007, .001, and .001, respectively).
• Improvement in quality of life was significant from baseline and similar between the FT and RE, with the exception of the “social aspects” domain, for which only the FT showed significant improvement.
• No intervention-related adverse events were reported in either group.

IN PRACTICE:

Despite the absence of consensus guidelines on the use and effectiveness of FT and RE, “we can conclude that both FT and RE have similar effectiveness in improving functional capacity, functional status, disease activity, general quality of life, and muscle strength in patients with psoriatic arthritis,” the researchers wrote.

SOURCE:

The study was led by Diego Roger Silva, MD, of the Universidade Federal de São Paulo, Brazil, and published online in Advances in Rheumatology.

LIMITATIONS:

The study population was recruited from outpatient clinics, and the mean age of 52 years was higher than in previous studies; the study also lacked long-term follow-up data.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Exercise with weight machines or elastic resistance bands yielded similar improvements in strength and function in adults with psoriatic arthritis (PsA) after 12 weeks.

METHODOLOGY:

• Researchers recruited 41 adults aged 18-65 years with PsA who were then randomized to a functional training group (FT) or a resistance exercise group (RE) for 12 weeks of twice-weekly, 55-minute sessions under the supervision of a physical trainer.
• Functional training involved the use of elastic bands to work upper body, lower body, and trunk muscles including the biceps, triceps, back quadriceps, glutes, and hips; the RE used weight machines instead of bands.
• Participants were evaluated at baseline and after 6 and 12 weeks of training sessions; the primary outcome was functional status based on the Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S).
• Secondary outcomes included the Bath Ankylosing Spondylitis Functional Index (BASFI) to assess functional capacity, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Disease Activity Score in 28 joints (DAS28) to assess disease activity, and the Short Form 36 (SF-36) to measure quality of life.

TAKEAWAY:

• Participants in both groups showed significant improvement from baseline on the primary outcome measure, with no significant differences between the groups on the primary outcome of function or secondary measures of function and disease activity after 12 weeks.
• Significant intragroup changes occurred between times for both groups on the HAQ-S, BASFI, BASDAI, and DAS28 (P = .001, .007, .001, and .001, respectively).
• Improvement in quality of life was significant from baseline and similar between the FT and RE, with the exception of the “social aspects” domain, for which only the FT showed significant improvement.
• No intervention-related adverse events were reported in either group.

IN PRACTICE:

Despite the absence of consensus guidelines on the use and effectiveness of FT and RE, “we can conclude that both FT and RE have similar effectiveness in improving functional capacity, functional status, disease activity, general quality of life, and muscle strength in patients with psoriatic arthritis,” the researchers wrote.

SOURCE:

The study was led by Diego Roger Silva, MD, of the Universidade Federal de São Paulo, Brazil, and published online in Advances in Rheumatology.

LIMITATIONS:

The study population was recruited from outpatient clinics, and the mean age of 52 years was higher than in previous studies; the study also lacked long-term follow-up data.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

Treatment of enthesitis can be challenging. Head-to-head clinical trials using clinical enthesitis indices have indicated that TNF inhibitors and IL-17 inhibitors have similar efficacy in treating enthesitis. However, clinically determined enthesitis may not be true inflammatory enthesitis. Ultrasonography-confirmed enthesitis probably reflects true enthesitis. Therefore, Elliot and colleagues conducted an observational study that compared the change in MAdrid Sonographic Enthesitis Index (MASEI) at 16 weeks of treatment with either TNF inhibitors or secukinumab. They observed that the mean reduction in MASEI that assesses both active and chronic entheseal disease was not significantly different with TNF inhibitors vs secukinumab treatment. However, TNF inhibitors were significantly more effective than secukinumab when only active entheseal lesions were considered. Thus, TNF inhibitors may be more effective for active enthesitis; randomized trials using ultrasonographic enthesitis indices comparing the two treatments are required.

Serum drug levels have previously been shown to be associated with response to bDMARD therapy, but use of drug-level measurement is not routine in rheumatology practice. Moreover, trough levels are emphasized and may not often be feasible to obtain. Curry and colleagues investigated the relationship between serum non-trough drug levels (SDL) and treatment response at 3 months in patients with PsA who initiated treatment with adalimumab (n = 104) or etanercept (n = 97). They demonstrated that patients with higher etanercept SDL or higher adalimumab SDL were significantly more likely to be responders. A non-trough etanercept SDL of 2.0 µg/mL and adalimumab SDL of 3.6 µg/mL could differentiate between responders and nonresponders with ~50% specificity and > 60% sensitivity. However, the area under the receiver operating characteristic curves were only about 65%; thus, the ability of SDL to discriminate between responders and nonresponders is low.

Treatment of enthesitis can be challenging. Head-to-head clinical trials using clinical enthesitis indices have indicated that TNF inhibitors and IL-17 inhibitors have similar efficacy in treating enthesitis. However, clinically determined enthesitis may not be true inflammatory enthesitis. Ultrasonography-confirmed enthesitis probably reflects true enthesitis. Therefore, Elliot and colleagues conducted an observational study that compared the change in MAdrid Sonographic Enthesitis Index (MASEI) at 16 weeks of treatment with either TNF inhibitors or secukinumab. They observed that the mean reduction in MASEI that assesses both active and chronic entheseal disease was not significantly different with TNF inhibitors vs secukinumab treatment. However, TNF inhibitors were significantly more effective than secukinumab when only active entheseal lesions were considered. Thus, TNF inhibitors may be more effective for active enthesitis; randomized trials using ultrasonographic enthesitis indices comparing the two treatments are required.

Serum drug levels have previously been shown to be associated with response to bDMARD therapy, but use of drug-level measurement is not routine in rheumatology practice. Moreover, trough levels are emphasized and may not often be feasible to obtain. Curry and colleagues investigated the relationship between serum non-trough drug levels (SDL) and treatment response at 3 months in patients with PsA who initiated treatment with adalimumab (n = 104) or etanercept (n = 97). They demonstrated that patients with higher etanercept SDL or higher adalimumab SDL were significantly more likely to be responders. A non-trough etanercept SDL of 2.0 µg/mL and adalimumab SDL of 3.6 µg/mL could differentiate between responders and nonresponders with ~50% specificity and > 60% sensitivity. However, the area under the receiver operating characteristic curves were only about 65%; thus, the ability of SDL to discriminate between responders and nonresponders is low.

Treatment of enthesitis can be challenging. Head-to-head clinical trials using clinical enthesitis indices have indicated that TNF inhibitors and IL-17 inhibitors have similar efficacy in treating enthesitis. However, clinically determined enthesitis may not be true inflammatory enthesitis. Ultrasonography-confirmed enthesitis probably reflects true enthesitis. Therefore, Elliot and colleagues conducted an observational study that compared the change in MAdrid Sonographic Enthesitis Index (MASEI) at 16 weeks of treatment with either TNF inhibitors or secukinumab. They observed that the mean reduction in MASEI that assesses both active and chronic entheseal disease was not significantly different with TNF inhibitors vs secukinumab treatment. However, TNF inhibitors were significantly more effective than secukinumab when only active entheseal lesions were considered. Thus, TNF inhibitors may be more effective for active enthesitis; randomized trials using ultrasonographic enthesitis indices comparing the two treatments are required.

Serum drug levels have previously been shown to be associated with response to bDMARD therapy, but use of drug-level measurement is not routine in rheumatology practice. Moreover, trough levels are emphasized and may not often be feasible to obtain. Curry and colleagues investigated the relationship between serum non-trough drug levels (SDL) and treatment response at 3 months in patients with PsA who initiated treatment with adalimumab (n = 104) or etanercept (n = 97). They demonstrated that patients with higher etanercept SDL or higher adalimumab SDL were significantly more likely to be responders. A non-trough etanercept SDL of 2.0 µg/mL and adalimumab SDL of 3.6 µg/mL could differentiate between responders and nonresponders with ~50% specificity and > 60% sensitivity. However, the area under the receiver operating characteristic curves were only about 65%; thus, the ability of SDL to discriminate between responders and nonresponders is low.

Patients with psoriasis being treated with biologics have a low overall risk for developing the paradoxical symptoms of eczema, with interleukin (IL)-23 inhibitors found to confer the lowest risk of the drug classes examined in a large observational analysis.

Using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) database, Ali Al-Janabi, MA, from the University of Manchester (England) and associates found that 273 (1%) of approximately 25,000 drug exposures in 13,699 biologic-treated patients with psoriasis were associated with paradoxical eczema.

The incidence of paradoxical eczema was found to vary by class. The highest rate was seen for IL-17 inhibitors, at 1.22 per 100,000 person-years, and the lowest rate was seen with IL-23 inhibitors, at 0.56 per 100,000 person-years. The respective incidence rates for tumor necrosis factor (TNF) inhibitors and IL-12/IL-23 inhibitors were a respective 0.94 and 0.80 per 100,000 person-years.

“Compared with TNF inhibitors, IL-23 inhibitor exposure was associated with significantly lower risk of paradoxical eczema,” the BADBIR Study Group reported in JAMA Dermatology. Indeed, patients treated with IL-23 inhibitors were 61% less likely than were those taking TNF-inhibitors to experience a paradoxical eczema event.

“These findings remained when restricting the analysis to first-line biologic exposures and were specific to this eczema phenotype” the group said.

Cautious Interpretation

As the corresponding author for the work, Mr. Al-Janabi observed in an email that the research needs to be replicated, and the findings need to be interpreted with caution.

“As well as usual clinical variables influencing biologic selection, clinicians could consider IL-23 inhibitors in patients with previous atopic dermatitis, hay fever, or paradoxical eczema episodes, as this class was associated with the lowest risk of paradoxical eczema,” he suggested.

A prior history of atopic dermatitis (AD) and hay fever appears to be particularly relevant, as both substantially upped the chances that paradoxical eczema would occur, with hazard ratios of 12.40 and 3.78, respectively. Increasing age also increased the risk, albeit slightly (hazard ratio [HR], 1.02 per year), and there was an apparent lower risk (HR, 0.60) comparing men and women.

The BADBIR Study Group authors believe that, to the best of their knowledge, this is the first study to compare paradoxical eczema risk by biologic class. “Based on clinical experience and prevalence of eczematous reactions reported in some IL-17 inhibitor clinical trials, we suspected an association between IL-17 inhibitor exposure and paradoxical eczema,” they wrote.

“While the incidence of paradoxical eczema was numerically highest among IL-17 inhibitor exposures, it was not significantly different from the incidence among TNF inhibitor exposures.” The low overall incidence of paradoxical eczema “may be reassuring for patients and clinicians,” they added, “but it is possible that the incidence was underestimated due to underreporting or exclusion of adverse events with insufficient detail.”

Details of the Analysis, Other Findings

To explore the risk of paradoxical eczema by biologic class and identify possible risk factors, the BADBIR Study Group performed a prospective cohort study using data held within the BADBIR database between September 2007 and December 2022.

Adults over the age of 18 year or older with plaque psoriasis and who had been treated with at least one of the following biologics were eligible for inclusion: the TNF inhibitors adalimumab, certolizumab pegol, etanercept, and infliximab; the IL-17 inhibitors bimekizumab, brodalumab, ixekizumab, and secukinumab; the IL-12/23 inhibitor ustekinumab; and the IL-23 inhibitors guselkumab, risankizumab, and tildrakizumab.

Patient records and adverse event data were reviewed to determine the incidence of paradoxical eczema events, using terms such as eczema, eczematized, eczematous, atopy, atopic, and dermatitis.

Of 24,952 drug exposures analyzed, the majority (11,819) were for TNF inhibitors, followed by IL-17 inhibitors (4,776), IL-12/23 inhibitors (6,423), and finally, IL-23 inhibitors (1,934).

Mr. Al-Janabi and coauthors reported that the median time to onset of paradoxical eczema events was 294 days — approximately 9.8 months. The earliest that these events were recorded was at 120 days (4 months), and the latest at 699 days (almost 2 years).

The face and neck were the most common sites affected (26% of exposures), with other sites including the limbs (23%), the trunk (13%), and hands or feet (12%). Itching (18%), redness (7%), and dryness (4%) were the most commonly reported symptoms.

The researchers noted that 21 patients had skin biopsies taken and “all showed spongiosis or a feature of eczema, with 1 having overlapping features of psoriasis.”

In the majority (92 %) of cases, patients experienced only one eczema event. Of the 20 patients who had more than one event, just over one-fifth of repeat events occurred after receiving the same biologic as for the index event. A quarter of events occurred after a different biologic of the same class had been used, and just over half of events occurred after a different class of biologic had been given.

Strengths and Limitations

The “large sample size and inclusion of multiple lines of exposure per participant” are strengths of the study, said the researchers. “We included data for all currently available biologics, originating from more than 160 dermatology centers in the UK and Ireland.”

They added, however, that the “main limitation is the small numbers of observations within certain subgroups, such as specific biologic exposures or participants in ethnic minority groups, restricting generalizability of our findings and the interpretation of some subgroup analyses.”

Moreover, the small number of paradoxical eczema events seen may have resulted in imprecise effect estimates, they observe, noting that the number of exposures to IL-23 inhibitors was low compared with other classes.

“Future studies with more exposures and paradoxical eczema events would enable a more robust analysis of individual drugs and patient subgroups,” the authors concluded.

The study was funded by the Medical Research Council. BADBIR is coordinated by The University of Manchester, and funded by the British Association of Dermatologists (BAD). The BAD receives income from AbbVie, Almirall, Amgen, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Samsung Bioepis, Sandoz Hexal AG, and UCB Pharma for providing pharmacovigilance services. This income finances a separate contract between the BAD and The University of Manchester, which coordinates BADBIR. Mr. Al-Janabi reported receiving grants from the Medical Research Council during the conduct of the study; nonfinancial support from UCB, Almirall, and Janssen; and personal fees from UCB outside the submitted work.

Patients with psoriasis being treated with biologics have a low overall risk for developing the paradoxical symptoms of eczema, with interleukin (IL)-23 inhibitors found to confer the lowest risk of the drug classes examined in a large observational analysis.

Using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) database, Ali Al-Janabi, MA, from the University of Manchester (England) and associates found that 273 (1%) of approximately 25,000 drug exposures in 13,699 biologic-treated patients with psoriasis were associated with paradoxical eczema.

The incidence of paradoxical eczema was found to vary by class. The highest rate was seen for IL-17 inhibitors, at 1.22 per 100,000 person-years, and the lowest rate was seen with IL-23 inhibitors, at 0.56 per 100,000 person-years. The respective incidence rates for tumor necrosis factor (TNF) inhibitors and IL-12/IL-23 inhibitors were a respective 0.94 and 0.80 per 100,000 person-years.

“Compared with TNF inhibitors, IL-23 inhibitor exposure was associated with significantly lower risk of paradoxical eczema,” the BADBIR Study Group reported in JAMA Dermatology. Indeed, patients treated with IL-23 inhibitors were 61% less likely than were those taking TNF-inhibitors to experience a paradoxical eczema event.

“These findings remained when restricting the analysis to first-line biologic exposures and were specific to this eczema phenotype” the group said.

Cautious Interpretation

As the corresponding author for the work, Mr. Al-Janabi observed in an email that the research needs to be replicated, and the findings need to be interpreted with caution.

“As well as usual clinical variables influencing biologic selection, clinicians could consider IL-23 inhibitors in patients with previous atopic dermatitis, hay fever, or paradoxical eczema episodes, as this class was associated with the lowest risk of paradoxical eczema,” he suggested.

A prior history of atopic dermatitis (AD) and hay fever appears to be particularly relevant, as both substantially upped the chances that paradoxical eczema would occur, with hazard ratios of 12.40 and 3.78, respectively. Increasing age also increased the risk, albeit slightly (hazard ratio [HR], 1.02 per year), and there was an apparent lower risk (HR, 0.60) comparing men and women.

The BADBIR Study Group authors believe that, to the best of their knowledge, this is the first study to compare paradoxical eczema risk by biologic class. “Based on clinical experience and prevalence of eczematous reactions reported in some IL-17 inhibitor clinical trials, we suspected an association between IL-17 inhibitor exposure and paradoxical eczema,” they wrote.

“While the incidence of paradoxical eczema was numerically highest among IL-17 inhibitor exposures, it was not significantly different from the incidence among TNF inhibitor exposures.” The low overall incidence of paradoxical eczema “may be reassuring for patients and clinicians,” they added, “but it is possible that the incidence was underestimated due to underreporting or exclusion of adverse events with insufficient detail.”

Details of the Analysis, Other Findings

To explore the risk of paradoxical eczema by biologic class and identify possible risk factors, the BADBIR Study Group performed a prospective cohort study using data held within the BADBIR database between September 2007 and December 2022.

Adults over the age of 18 year or older with plaque psoriasis and who had been treated with at least one of the following biologics were eligible for inclusion: the TNF inhibitors adalimumab, certolizumab pegol, etanercept, and infliximab; the IL-17 inhibitors bimekizumab, brodalumab, ixekizumab, and secukinumab; the IL-12/23 inhibitor ustekinumab; and the IL-23 inhibitors guselkumab, risankizumab, and tildrakizumab.

Patient records and adverse event data were reviewed to determine the incidence of paradoxical eczema events, using terms such as eczema, eczematized, eczematous, atopy, atopic, and dermatitis.

Of 24,952 drug exposures analyzed, the majority (11,819) were for TNF inhibitors, followed by IL-17 inhibitors (4,776), IL-12/23 inhibitors (6,423), and finally, IL-23 inhibitors (1,934).

Mr. Al-Janabi and coauthors reported that the median time to onset of paradoxical eczema events was 294 days — approximately 9.8 months. The earliest that these events were recorded was at 120 days (4 months), and the latest at 699 days (almost 2 years).

The face and neck were the most common sites affected (26% of exposures), with other sites including the limbs (23%), the trunk (13%), and hands or feet (12%). Itching (18%), redness (7%), and dryness (4%) were the most commonly reported symptoms.

The researchers noted that 21 patients had skin biopsies taken and “all showed spongiosis or a feature of eczema, with 1 having overlapping features of psoriasis.”

In the majority (92 %) of cases, patients experienced only one eczema event. Of the 20 patients who had more than one event, just over one-fifth of repeat events occurred after receiving the same biologic as for the index event. A quarter of events occurred after a different biologic of the same class had been used, and just over half of events occurred after a different class of biologic had been given.

Strengths and Limitations

The “large sample size and inclusion of multiple lines of exposure per participant” are strengths of the study, said the researchers. “We included data for all currently available biologics, originating from more than 160 dermatology centers in the UK and Ireland.”

They added, however, that the “main limitation is the small numbers of observations within certain subgroups, such as specific biologic exposures or participants in ethnic minority groups, restricting generalizability of our findings and the interpretation of some subgroup analyses.”

Moreover, the small number of paradoxical eczema events seen may have resulted in imprecise effect estimates, they observe, noting that the number of exposures to IL-23 inhibitors was low compared with other classes.

“Future studies with more exposures and paradoxical eczema events would enable a more robust analysis of individual drugs and patient subgroups,” the authors concluded.

The study was funded by the Medical Research Council. BADBIR is coordinated by The University of Manchester, and funded by the British Association of Dermatologists (BAD). The BAD receives income from AbbVie, Almirall, Amgen, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Samsung Bioepis, Sandoz Hexal AG, and UCB Pharma for providing pharmacovigilance services. This income finances a separate contract between the BAD and The University of Manchester, which coordinates BADBIR. Mr. Al-Janabi reported receiving grants from the Medical Research Council during the conduct of the study; nonfinancial support from UCB, Almirall, and Janssen; and personal fees from UCB outside the submitted work.

Patients with psoriasis being treated with biologics have a low overall risk for developing the paradoxical symptoms of eczema, with interleukin (IL)-23 inhibitors found to confer the lowest risk of the drug classes examined in a large observational analysis.

Using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) database, Ali Al-Janabi, MA, from the University of Manchester (England) and associates found that 273 (1%) of approximately 25,000 drug exposures in 13,699 biologic-treated patients with psoriasis were associated with paradoxical eczema.

The incidence of paradoxical eczema was found to vary by class. The highest rate was seen for IL-17 inhibitors, at 1.22 per 100,000 person-years, and the lowest rate was seen with IL-23 inhibitors, at 0.56 per 100,000 person-years. The respective incidence rates for tumor necrosis factor (TNF) inhibitors and IL-12/IL-23 inhibitors were a respective 0.94 and 0.80 per 100,000 person-years.

“Compared with TNF inhibitors, IL-23 inhibitor exposure was associated with significantly lower risk of paradoxical eczema,” the BADBIR Study Group reported in JAMA Dermatology. Indeed, patients treated with IL-23 inhibitors were 61% less likely than were those taking TNF-inhibitors to experience a paradoxical eczema event.

“These findings remained when restricting the analysis to first-line biologic exposures and were specific to this eczema phenotype” the group said.

Cautious Interpretation

As the corresponding author for the work, Mr. Al-Janabi observed in an email that the research needs to be replicated, and the findings need to be interpreted with caution.

“As well as usual clinical variables influencing biologic selection, clinicians could consider IL-23 inhibitors in patients with previous atopic dermatitis, hay fever, or paradoxical eczema episodes, as this class was associated with the lowest risk of paradoxical eczema,” he suggested.

A prior history of atopic dermatitis (AD) and hay fever appears to be particularly relevant, as both substantially upped the chances that paradoxical eczema would occur, with hazard ratios of 12.40 and 3.78, respectively. Increasing age also increased the risk, albeit slightly (hazard ratio [HR], 1.02 per year), and there was an apparent lower risk (HR, 0.60) comparing men and women.

The BADBIR Study Group authors believe that, to the best of their knowledge, this is the first study to compare paradoxical eczema risk by biologic class. “Based on clinical experience and prevalence of eczematous reactions reported in some IL-17 inhibitor clinical trials, we suspected an association between IL-17 inhibitor exposure and paradoxical eczema,” they wrote.

“While the incidence of paradoxical eczema was numerically highest among IL-17 inhibitor exposures, it was not significantly different from the incidence among TNF inhibitor exposures.” The low overall incidence of paradoxical eczema “may be reassuring for patients and clinicians,” they added, “but it is possible that the incidence was underestimated due to underreporting or exclusion of adverse events with insufficient detail.”

Details of the Analysis, Other Findings

To explore the risk of paradoxical eczema by biologic class and identify possible risk factors, the BADBIR Study Group performed a prospective cohort study using data held within the BADBIR database between September 2007 and December 2022.

Adults over the age of 18 year or older with plaque psoriasis and who had been treated with at least one of the following biologics were eligible for inclusion: the TNF inhibitors adalimumab, certolizumab pegol, etanercept, and infliximab; the IL-17 inhibitors bimekizumab, brodalumab, ixekizumab, and secukinumab; the IL-12/23 inhibitor ustekinumab; and the IL-23 inhibitors guselkumab, risankizumab, and tildrakizumab.

Patient records and adverse event data were reviewed to determine the incidence of paradoxical eczema events, using terms such as eczema, eczematized, eczematous, atopy, atopic, and dermatitis.

Of 24,952 drug exposures analyzed, the majority (11,819) were for TNF inhibitors, followed by IL-17 inhibitors (4,776), IL-12/23 inhibitors (6,423), and finally, IL-23 inhibitors (1,934).

Mr. Al-Janabi and coauthors reported that the median time to onset of paradoxical eczema events was 294 days — approximately 9.8 months. The earliest that these events were recorded was at 120 days (4 months), and the latest at 699 days (almost 2 years).

The face and neck were the most common sites affected (26% of exposures), with other sites including the limbs (23%), the trunk (13%), and hands or feet (12%). Itching (18%), redness (7%), and dryness (4%) were the most commonly reported symptoms.

The researchers noted that 21 patients had skin biopsies taken and “all showed spongiosis or a feature of eczema, with 1 having overlapping features of psoriasis.”

In the majority (92 %) of cases, patients experienced only one eczema event. Of the 20 patients who had more than one event, just over one-fifth of repeat events occurred after receiving the same biologic as for the index event. A quarter of events occurred after a different biologic of the same class had been used, and just over half of events occurred after a different class of biologic had been given.

Strengths and Limitations

The “large sample size and inclusion of multiple lines of exposure per participant” are strengths of the study, said the researchers. “We included data for all currently available biologics, originating from more than 160 dermatology centers in the UK and Ireland.”

They added, however, that the “main limitation is the small numbers of observations within certain subgroups, such as specific biologic exposures or participants in ethnic minority groups, restricting generalizability of our findings and the interpretation of some subgroup analyses.”

Moreover, the small number of paradoxical eczema events seen may have resulted in imprecise effect estimates, they observe, noting that the number of exposures to IL-23 inhibitors was low compared with other classes.

“Future studies with more exposures and paradoxical eczema events would enable a more robust analysis of individual drugs and patient subgroups,” the authors concluded.

The study was funded by the Medical Research Council. BADBIR is coordinated by The University of Manchester, and funded by the British Association of Dermatologists (BAD). The BAD receives income from AbbVie, Almirall, Amgen, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Samsung Bioepis, Sandoz Hexal AG, and UCB Pharma for providing pharmacovigilance services. This income finances a separate contract between the BAD and The University of Manchester, which coordinates BADBIR. Mr. Al-Janabi reported receiving grants from the Medical Research Council during the conduct of the study; nonfinancial support from UCB, Almirall, and Janssen; and personal fees from UCB outside the submitted work.