Long-term Risankizumab Treatment Outperforms Placebo in PsA

Joseph Merola, MD, MMSc

Credit: Lupus Foundation

A post hoc analysis of the phase 3 KEEPsAKE 1 and KEEPsAKE 2 trials evaluating risankizumab treatment in patients with psoriatic arthritis (PsA) showed greater efficacy when compared with placebo, according to research published in Journal of Dermatological Treatment.¹

“Recent guidelines (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the European League Against Rheumatism, and the American College of Rheumatology/National Psoriasis Foundation) endorse a specialized treatment approach for patients with PsA and other underlying comorbidities,” wrote a team of investigators led by Joseph Merola, MD, MMSc, associated with the Department of Dermatology at Brigham and Women’s Hospital, Harvard Medical School. “However, an unmet need remains for new treatment options that provide durable efficacy in a variety of patients, across heterogeneous patient demographics and clinical characteristics.”

Although advancements in PsA have led to the development of a number of treatments for this patient population, those with other comorbidities or prior exposure to biologic therapies could experience lower levels of efficacy.²

Risankizumab, a fully humanized immunoglobulin G1 monoclonal antibody that specifically inhibits interleukin (IL)-23 by binding to the p19 subunit, has been proven to be an effective treatment for PsA. This analysis determined long-term efficacy of the drug among clinically relevant subgroups stratified by age, sex, race, body mass index, and disease characteristics up to 52 weeks.

The study focused on the proportion of patients who were able to achieve ≥ 20%/50%/70% improvement in the American College of Rheumatology response criteria (ACR20/50/70), minimal disease activity status, low disease activity status, minimal clinically important difference in pain, and ≥ 90% improvement in the Psoriasis Area and Severity Index (PASI) at week 24 and week 52 compared with baseline demographics and clinical characteristics.

Eligible patients were aged ≥ 18 years, had a clinically confirmed PsA diagnosis, and an inadequate response or intolerance to biologic therapies and/or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

In both trials, patients were randomized 1:1 to receive subcutaneous risankizumab 150 mg or placebo at weeks 0, 4, and 16. At week 24, those in the placebo group were switched to risankizumab 150 mg and those in the risankizumab cohort received a single, double-blinded dose of placebo. At week 28, all patients were treated with risankizumab every 12 weeks for up to 52 weeks.

Within the sample, baseline characteristics and demographics were comparable among patients receiving risankizumab (n = 707) and placebo (n = 700). Approximately half (47.8% — 55.4%) were female, the mean age ranged from 51.2 to 53.1 years, the mean PASI scores were 7.7 to 10.9, and the mean body mass index scores ranged from 30.3 to 31.5.

At week 24, numerically higher ACR20 response rates were reported in the risankizumab cohort (46.3% — 60.1%) compared with the placebo cohort (15.5% — 36.2%), regardless of subgroup categorization.

At the 52-week mark, consistent proportions of patients randomized to risankizumab were able to achieve ACR20 (48.6% — 75.8%). Additionally, those initially treated with placebo who were then switched to risankizumab reported a similar improvement from week 24 (43.7% — 63.9%), regardless of subgrouping.

These trends were also noted among other efficacy measures, including those evaluating skin response criteria, composite measures of overall disease activity, and PsA-related symptoms. Treatment with risankizumab was shown to be an effective strategy among patients with PsA regardless of varying demographic and psoriatic disease characteristics through 1 year.

Investigators noted the relatively small sample size among a few subgroups as a limitation of the study, which may have led to more imprecise estimates of treatment effects. They encourage future research to examine real-world patient data to confirm if results are generalizable to the general population.

“These efficacy results support long-term use of risankizumab for patients with active PsA across multiple patient and psoriatic disease characteristics,” investigators concluded.

References

1. ^{Merola JF, Armstrong A, Khattri S, et al. Efficacy of risankizumab across subgroups in patients with active psoriatic arthritis: a post hoc integrated analysis of the phase 3 KEEPsAKE 1 and KEEPsAKE 2 randomized controlled trials. J Dermatolog Treat. 2024;35(1):2342383. doi:10.1080/09546634.2024.2342383}
2. ^{Kumthekar A, Ogdie A. Obesity and psoriatic arthritis: a narrative review. Rheumatol Ther. 2020;7(3):447–−456. doi:10.1007/s40744-020-00215-6.}