Maintenance of Response to Risankizumab in Patients With Psoriatic Arthritis: A 5-year Analysis of the KEEPsAKE 1 and 2 Trials

Abstract

Introduction & Objectives: Risankizumab (RZB) is a humanized immunoglobulin G1 monoclonal antibody that inhibits interleukin-23 (IL-23) by targeting its p19 subunit. This post hoc analysis evaluated the maintenance of clinical responses after approximately 5 years of RZB treatment in patients enrolled in the ongoing phase 3 KEEPsAKE 1 and KEEPsAKE 2 clinical trials.

Materials & Methods: Eligibility for enrollment required patients to have active PsA and inadequate response or intolerance to ≥ 1 conventional synthetic disease modifying antirheumatic drug (csDMARD) for KEEPsAKE 1 (NCT03675308), or inadequate response or intolerance to 1 or 2 biologic DMARDs and/or ≥ 1 csDMARD for KEEPsAKE 2 (NCT03671148). In both studies, patients were initially randomized 1:1 to receive RZB 150 mg or placebo for a 24-week double-blind period and received open-label RZB thereafter. Maintenance of response analyses were based on patients who were responders at week 24 for each endpoint. Assessments included improvement of ≥ 20%/50%/70% in PsA symptoms using the American College of Rheumatology criteria (ACR20/50/70), achievement of minimal disease activity (MDA), reduction of ≥ 90% in Psoriasis Area and Severity Index (PASI90; in patients with ≥ 3% body surface area affected by psoriasis at baseline), clinically meaningful reduction in pain≥ 10 mm on a visual analog scale [VAS] in patients with > 10 mm at baseline), chievement of the MDA patient pain criteria (VAS ≤ 15 mm in patients with VAS > 15 mm at baseline), and clinically meaningful reduction in modified Bath Ankylosing Spondylitis Disease Activity Index (mBASDAI; ≥ 1.1 point-decrease in patients with a score > 1.1 at baseline). Nonresponder imputation incorporating multiple imputation (NRI-MI) was used with data missing due to COVID-19 or geopolitical conflict; all other missing data were imputed as nonresponders. Safety assessments of the overall population have been performed in previous studies.

Results: The majority of patients who received RZB during the double-blind period and achieved ACR20 at week 24 maintained ACR20 at week 244 (KEEPsAKE 1: 66.7%; KEEPsAKE 2: 64.0%). Achievement of ACR50 (KEEPsAKE 1: 55.0%; KEEPsAKE 2: 56.1%) and ACR70 (KEEPsAKE 1: 52.2%; KEEPsAKE 2: 61.5%) was similarly maintained at week 244 for patients randomized to continuous RZB. Most week 24 responders maintained achievement of MDA (KEEPsAKE 1: 63.6%; KEEPsAKE 2: 64.9%) and PASI90 (KEEPsAKE 1: 71.5%; KEEPsAKE 2: 72.5%) at week 244. Clinically meaningful reductions in pain (KEEPsAKE 1: 66.1%; KEEPsAKE 2: 58.4%) and achievement of the MDA patient pain criteria (KEEPsAKE 1: 60.4%; KEEPsAKE 2: 48.8%) were maintained at week 244. Most patients maintained clinically meaningful reductions in mBASDAI score from week 24 to week 244 (pooled KEEPsAKE 1 and KEEPsAKE 2: 62.5%).

Conclusion: RZB demonstrated durable long-term efficacy across multiple clinical endpoints among patients with active PsA. Among RZB-treated patients who achieved treatment response targets at week 24, those responses were maintained at week 244.