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Clinical Trials, psoriatic arthritis, risankizumab
Introduction: Risankizumab, a humanized immunoglobulin G1 monoclonal antibody, specifically inhibits the p19 subunit of human interleukin 23 and is approved for treatment of active psoriatic arthritis (PsA) in adults. This post hoc analysis evaluated the long-term maintenance of clinical response through ~3 years of risankizumab treatment using data from 2 ongoing phase 3 trials, KEEPsAKE 1 and KEEPsAKE 2.
Methods: Eligible patients had active PsA with inadequate response or intolerance to ≥1 conventional synthetic disease modifying antirheumatic drugs (KEEPsAKE 1 [NCT03675308]; KEEPsAKE 2 [NCT03671148]) and/or inadequate response or intolerance to 1–2 biologic therapies (KEEPsAKE 2 only). Patients received double-blinded risankizumab 150 mg or placebo at weeks 0, 4, and 16 and open-label risankizumab 150 mg every 12 weeks thereafter. This analysis includes patients who received continuous risankizumab through both treatment periods. Assessments included improvement of ≥20%/50%/70% in PsA symptoms using American College of Rheumatology criteria (ACR20/50/70), achievement of minimal disease activity (MDA), reduction of ≥90% in Psoriasis Area and Severity Index (PASI 90; in patients with ≥3% body surface area affected by psoriasis at baseline), and clinically meaningful reduction in pain (≥10 mm on a visual analog scale [VAS]). Maintenance of response analyses were based on patients who were responders at weeks 24 or 52 for each endpoint. Nonresponder imputation incorporating multiple imputation (NRI-MI) for missing data due to COVID-19 or geopolitical conflict was used. As-observed data were also reported.
Results: Among patients receiving continuous risankizumab, ACR20 was achieved at week 24 in 267/454 (KEEPsAKE 1, 58.8%) and 111/208 (KEEPsAKE 2, 53.4%) patients (as observed). Maintenance of response in week 24 ACR20 responders (NRI-MI) was achieved for ACR20 by most patients at week 52 (KEEPsAKE 1, 89.1%; KEEPsAKE 2, 77.0 %) and week 148 (KEEPsAKE 1, 74.7%; KEEPsAKE 2; 68.5%). Similar patterns of maintenance of response were observed for ACR50 and ACR70. Week 24 responders also maintained MDA at weeks 52 (KEEPsAKE 1, 82.2%; KEEPsAKE 2, 66.7%) and 148 (KEEPsAKE 1, 77.1%; KEEPsAKE 2, 71.9%). The PASI 90 response was maintained at weeks 52 (KEEPsAKE 1, 86.6%; KEEPsAKE 2, 88.4%) and 148 (KEEPsAKE 1, 76.3%; KEEPsAKE 2, 81.2%). Week 24 responders maintained clinically meaningful reductions in pain VAS at weeks 52 (KEEPsAKE 1, 83.9%; KEEPsAKE 2, 74.4%) and 148 (KEEPsAKE 1, 75.0%; KEEPsAKE 2, 72.0%). Comparable maintenance of response was recorded at week 148 for each endpoint among week 52 responders (NRI-MI).
Conclusion: Risankizumab demonstrated durable long-term efficacy in patients with active PsA. A high proportion of patients receiving continuous risankizumab treatment in KEEPsAKE 1 and KEEPsAKE 2 achieved responses in ACR20/50/70, MDA, PASI 90, or pain VAS at weeks 24 or 52 and maintained responses through week 148.
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