Drugs Affecting the IL-23 Pathway May Lower Risk of Psoriatic, Inflammatory Arthritis From Psoriasis

Treatment with interleukin (IL)-12/23 inhibitors or IL-23 inhibitors is linked with a lower risk of progression to inflammatory arthritis in patients with psoriasis compared with tumor necrosis factor (TNF) inhibitors, new research shows. Findings of the retrospective cohort study were published in The Lancet Rheumatology.

However, the study’s researchers note that prospective observational cohorts with disease activity measures and pooled analyses of prior randomized trials are warranted to confirm the findings.

Previous research shows targeted biological immunotherapies are effective for psoriasis and can improve patients’ quality of life. But around a quarter of patients with the condition go on to develop psoriatic arthritis and response rates for biologics to control joint symptoms in these patients have been less impressive, the researchers explained.

Therefore, identifying strategies to prevent progression from psoriasis to psoriatic arthritis is paramount.

To better understand the role of biological immunotherapy in delaying progression to psoriatic arthritis in these patients, the investigators assessed data from a national sample of patients in the United States from the TriNetX database.

All patients had 1 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or ICD-10-CM codes for psoriasis that were separated by more than 30 days and had been newly prescribed an FDA-approved biologic approved. These include infliximab, adalimumab, etanercept, golimumab, certolizumab pegol, guselkumab, risankizumab, tildrakizumab, ustekinumab, secukinumab, ixekizumab, or brodalimumab.

Participants were at least 18 years old, and 15,501 patients with psoriasis were included in the final analysis. The mean (SD) patient age was 50.2 (15.0) years, and 54.2% were women. Most participants (72.1%) were White. Data were collected between January 1, 2014, and June 1, 2022.

In total, 976 individuals (6.3%) developed inflammatory arthritis, with a cumulative incidence of 2.6 cases per 100 person-years, authors said.

Data showed:

• In multivariable regression analyses, the risk of developing inflammatory arthritis was significantly lower in patients prescribed IL-12/23 inhibitors (adjusted HR, 0.58; 95% CI, 0.43-0.76) or IL-23 inhibitors (HR, 0.41; 95% CI, 0.17-0.95) than in patients prescribed TNF inhibitors
• There was no significant difference for IL-17 inhibitors (HR, 0.86; 95% CI, 0.54-1.38) vs TNF inhibitors
• For IL-12/23 inhibitors, the results persisted in all sensitivity analyses
• For IL-23 inhibitors, the results persisted in 3 of 6 sensitivity analyses, when a higher diagnostic threshold for incident arthritis was used and when excluding patients who developed arthritis within 3 or 6 months after their first biologic prescription

To the authors’ knowledge, the study is the first to compare the risk of incident inflammatory arthritis among patients who newly received biological disease-modifying antirheumatic drugs. The study is also the first to indicate a link between specific biological pathways and risk of inflammatory arthritis, they added.

Findings should be interpreted with caution, as any undercoding of inflammatory arthritis could have predisposed patients with early psoriatic arthritis to receive TNF inhibitors, as this was the first class of medications to receive FDA approval for psoriatic arthritis.

“Conversely, patients with greater skin severity (ie, severe psoriasis), which is a known risk factor for the development of psoriatic arthritis, might have been less likely to receive TNF inhibitors due to clinician preference for IL-23 or IL-17 inhibitors for severe psoriasis,” the authors said. However, they attempted to mitigate these issues by requiring 1 year of follow-up before the index date, so as to include only patients with no previous codes for any type of arthritis.

Overall, the risk of incident psoriatic or inflammatory arthritis was lower in patients who received drugs that affect the IL-23 pathway compared with TNF inhibitors, the researchers concluded.

“Additional analyses should be done to corroborate these results, with use of observational cohorts that have disease activity measures and via pooled analyses of previous randomized trials. In the interim, the present results support other evidence favoring non-TNF biologics as a first-line therapy for psoriasis,” they said.

Reference

Singla S, Putman M, Liew J, Gordon K. Association between biological immunotherapy for psoriasis and time to incident inflammatory arthritis: a retrospective cohort study. Lancet Rheumatol. Published online March 20, 2023. doi:10.1016/S2665-9913(23)00034-6