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Over the course of 16 weeks, patients with psoriatic arthritis (PsA) receiving risankizumab reported improved joint and skin symptoms when compared with placebo. Improvements were maintained long-term, and the drug was well tolerated with no new safety issues, according to a study published in Springer.1
“Interleukin-23 (IL-23), a key regulator of multiple effector cytokines, has been implicated in the pathogenesis of psoriatic skin lesions, synovitis, enthesitis, and bone erosion, making IL-23 inhibitors candidates for the treatment of PsA,” investigators stated. “Risankizumab, a humanized immunoglobulin G1 monoclonal antibody that inhibits IL-23 by binding to its p19 subunit, has been approved for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.”
In the phase 2, double-blind, dose-ranging study, eligible patients with active PsA (≥ 5 tender joints and ≥ 5 swollen joints) for 6 or more months were randomized 2:2:2:1:2 to receive risankizumab 150 mg at weeks 0, 4, 8, 12, and 16, 150 mg at weeks 0, 4, and 16, 150 mg at weeks 0 and 12, 75 mg at week 0, or placebo. Those who completed week 24 were able to receive risankizumab 150 mg every 12 weeks for 36 weeks as a part of a 52-week open-label extension study. The extension study also included follow-up visits at week 48 and week 52. The primary endpoint was efficacy as determined by American College of Rheumatology (ACR) responses. Secondary endpoints included ACR20/50/70 responses at week 16, Psoriasis Area Severity Index (PASI) responses, 28-joint Disease Activity Score base don C-reactive protein (DAS289[CRP]), and minimal disease activity (MDA).
Most (93.5%) patients (n = 173/185) completed week 16 and 78.5% (n = 145) were able to enter the open-label extension. Demographics were similar between the participants in the core study. The mean age was 49 years, PsA disease duration was 6.7 years, and 42.9% of patients were female in the group receiving the placebo.
A significant number of patients in arm 1 and 2 of the risankizumab cohorts achieved ACR20 at week 16 when compared with placebo (50/84 [59.5%; 90% CI 50.0–68.6]; treatment difference [90% CI] 24.0 [9.3, 38.7]; P = 0.007). Further, significantly more patients in the risankizumab groups were able to achieve ACR20/50/70, PASI75/90/100, MDA, and greater improvements in DAS28(CRP) when compared with placebo at week 16. ACR20/50/70 response rates increased throughout the open-label extension, with 75.2%, 43.6%, and 24.8% achieving these goals, respectively. PASI75/90/100 responses increased from 82.9%, 73.2%, and 61.0%, respectively. Benefits of risankizumab were able to be sustained long-term. Risankizumab 150 mg was well tolerated over the course of the 76-week open-label extension trial.
The small patient population limited the precision of the outcomes and accuracy of the translation of the results. The 2:2:2:1:2 randomization method included the smallest number of patients in the low-dose cohort. Additionally, the study did not test differences across the treatment arms. However, assessing the key domains of PsA and confirmed efficacy of IL-23 inhibitors strengthened the study.
“Improvements were maintained over the long term among patients who enrolled in the open-label extension study,” investigators concluded. “Overall, the findings of this study demonstrated that risankizumab was well tolerated, reduced the signs and symptoms of psoriasis and arthritis, and inhibited the progression of joint damage over the long term in patients with active PsA. These results supported further evaluation of risankizumab for the treatment of PsA in a phase 3 program.”
Mease PJ, Kellner H, Morita A, et al. Long-Term Efficacy and Safety of Risankizumab in Patients with Active Psoriatic Arthritis: Results from a 76-Week Phase 2 Randomized Trial [published online ahead of print, 2022 Aug 5]. Rheumatol Ther. 2022;10.1007/s40744-022-00474-5. doi:10.1007/s40744-022-00474-5