Long-Term Efficacy and Safety of Risankizumab in Patients with Active Psoriatic Arthritis: Results from a 76-Week Phase 2 Randomized Trial

Abstract

Introduction: The objective of this work was to assess the efficacy and safety of risankizumab in psoriatic arthritis (PsA) over 76 weeks.

Methods: In this double-blind, dose-ranging phase 2 study, adults with active PsA were randomized 2:2:2:1:2 to risankizumab 150 mg at weeks 0, 4, 8, 12, and 16 (arm 1), 150 mg at weeks 0, 4, and 16 (arm 2), 150 mg at weeks 0 and 12 (arm 3), 75 mg at week 0 (arm 4), or placebo (arm 5). Patients completing week 24 could receive risankizumab 150 mg in a 52-week open-label extension study. Efficacy assessments included American College of Rheumatology (ACR) responses, Psoriasis Area Severity Index (PASI) responses, minimal disease activity (MDA), and 28-joint Disease Activity Score based on C-reactive protein (DAS28[CRP]).

Results: Of 185 randomized patients, 173 (93.5%) completed week 16 and 145 (78.4%) entered the open-label extension. Significantly more patients in each risankizumab arm achieved ACR20 at week 16 versus placebo (primary endpoint: pooled arms 1 + 2 [59.5%] versus placebo [35.7%]; treatment difference [90% CI] 24.0 [9.3, 38.7]; P = 0.007). Similarly, significantly more patients in most risankizumab arms achieved ACR20/50/70, PASI75/90/100, MDA, and greater improvements in DAS28(CRP) versus placebo at week 16. These benefits of risankizumab were maintained long term. Treatment-emergent adverse events were comparable across treatment arms. Risankizumab 150 mg was well tolerated over 76 weeks.

Conclusions: Risankizumab improved joint and skin symptoms versus placebo in patients with active PsA over 16 weeks; improvements were sustained long term. Risankizumab was well tolerated over the long term with no new safety findings.

Trial registration numbers: NCT02719171 and NCT02986373.

Keywords: Interleukins; Psoriatic arthritis; Randomized trial; Risankizumab.

© 2022. The Author(s).

Figures

Fig. 1

Study design. ACR20 American College of Rheumatology 20 criteria response, mTSS modified Total Sharp Score, OLE open-label extension, RZB risankizumab, s.c. subcutaneous

Fig. 2

Patient disposition. *Percentages are shown using originally randomized patients (N = 185) as denominator/OLE patients (n = 145) as denominator. OLE open-label extension, RZB risankizumab

Fig. 3

Percentage of patients achieving ACR20/50/70 responses at week 16 (a), PASI75/90/100 responses at week 16 among patients with ≥ 3% BSA at baseline (b), and percentage of patients achieving MDA at week 16 among all patients (c). ACR American College of Rheumatology, BSA body surface area, MDA minimal disease activity, NRI non-responder imputation, PASI Psoriasis Area Severity Index, TNF tumor necrosis factor. NRI analyses. The difference in response rates between groups as well as the two-sided P value were calculated using Cochran–Mantel–Haenszel risk difference estimate stratified by prior TNF inhibitor use and concurrent methotrexate use. Statistical comparison versus placebo: ***P ≤ 0.001; **P ≤ 0.01; *P ≤ 0.05