Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial

Abstract

ObjectiveTo evaluate risankizumab, a biological therapy that inhibits interleukin 23, in patients with active psoriatic arthritis (PsA) who have responded inadequately or are intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD).MethodsIn the randomised, placebo-controlled, double-blind KEEPsAKE 1 trial, 964 patients with active PsA were randomised (1:1) to receive risankizumab 150 mg or placebo at weeks 0, 4 and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Here, we report the results from the 24-week double-blind period; the open-label period with all patients receiving risankizumab is ongoing.ResultsAt week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (57.3% vs placebo, 33.5%; p<0.001). Significant differences were also observed for risankizumab versus placebo for the first eight ranked secondary endpoints, including skin and nail psoriasis endpoints, minimal disease activity and resolution of enthesitis and dactylitis (p<0.001). Adverse events and serious adverse events were reported at similar rates in the risankizumab and placebo groups. Serious infections were reported for 1.0% and 1.2% of patients receiving risankizumab and placebo, respectively. There was one death in the risankizumab group (urosepsis deemed unrelated to the study drug).ConclusionsRisankizumab treatment results in significantly greater improvement of signs and symptoms of PsA compared with placebo and is well tolerated in patients with active PsA who have responded inadequately or are intolerant to ≥1 csDMARD.Trial registration numberNCT03675308.

Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial

“…These results are consistent with the pooled results from KEEPsAKE 1 and 2 previously reported. 29 Additionally, a significantly greater proportion of patients treated with risankizumab versus placebo achieved PASI 90 at week 24 (55.0% vs 10.2%, p<0.001); a difference was observed as early as week 4 ( figure 2D ).…”

“…Multiple agents that target IL-23 or its downstream pathway component, IL-17, are approved to treat PsA. 10 Data from the KEEPsAKE 1 29 and KEEPsAKE 2 trials provide further evidence that specifically targeting the p19 subunit of IL-23 is an effective therapeutic strategy to treat PsA. Notably, similar efficacy was observed with or without background csDMARDs or methotrexate for patients treated with risankizumab (ACR20 response rates, 48% for csDMARDs other than methotrexate and 51% for any methotrexate vs 53% for no csDMARD; online supplemental table 4 ).…”

“…Pooled data for these endpoints were analysed under the multiplicity control of KEEPsAKE 1 and are reported separately. 29 A multiple testing procedure was used to control the type I error rate by comparing risankizumab versus placebo in a fixed hypothesis testing procedure that began with the primary endpoint, proceeded through the ranked secondary endpoints in sequence, and continued until an endpoint did not achieve statistical significance. For categorical efficacy endpoints, missing data were handled by non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C).…”

New and Emerging Targeted Therapies for Hidradenitis Suppurativa

“…Risankizumab is a fully human IgG1κ monoclonal antibody that neutralizes the IL-23 [ 139 ]. It is FDA-approved for use in adults with psoriasis and/or psoriatic arthritis [ 140 ].…”

Comprehensive Review Exploring Novel Treatments for Psoriatic Arthritis and Axial Spondyloarthritis from 2016 to 2021

“…5,6 The primary endpoint of a 20% improvement in the number of tender and number of swollen joints and a 20% improvement in three of five criteria (ACR20) at 24 weeks was seen in 39.4% of patients in the abatacept arm versus 22.3% in the placebo arm (Table 1). [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] At week 16, those who did not achieve ACR20 responses were switched to open-label abatacept. After 24 weeks, all remaining patients were placed on open-label abatacept for an additional 28 weeks, and the ACR20 results became more equal between the two groups.…”