Dataset Information

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

ABSTRACT:

Objective

To 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).

Methods

In 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.

Results

At 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).

Conclusions

Risankizumab 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 number

NCT03675308.

SUBMITTER: Kristensen LE

PROVIDER: S-EPMC8762015 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionRisankizumab is an anti-IL23 monoclonal antibody approved for the treatment of moderate to severe plaque psoriasis and active psoriatic arthritis (PsA). This work characterizes the pharmacokinetics of risankizumab in PsA compared with psoriasis and evaluates the efficacy and safety exposure-response relationships in PsA.MethodsThe population pharmacokinetic analyses included data from 1527 participants that originated from one phase 1 healthy participant study, one phase 2 dose-ranging study in patients with PsA with an open-label extension study, and two pivotal phase 3 studies in patients with PsA, where the clinical regimen of risankizumab 150 mg administered subcutaneously (SC) at weeks 0, 4, and every 12 weeks thereafter was compared with placebo. Pharmacokinetics were analyzed using nonlinear mixed-effects modeling. Simulation analyses using the final model were conducted to evaluate the impact of covariates on exposure. Data from 1407 patients with PsA from the phase 3 studies were included in the exposure-response analyses. Graphical analyses were used to evaluate efficacy and safety exposure-response relationships, and logistic regression was conducted for further assessment of efficacy exposure-response relationships.ResultsRisankizumab pharmacokinetics were well described by a two-compartment model with first-order SC absorption and elimination. None of the evaluated covariates showed clinically relevant impact on exposure. On the basis of the final model, systemic clearance, steady-state volume of distribution, and terminal phase elimination half-life were estimated to be ~ 0.31 L/day, 11.1 L, and 26.3 days, respectively, for a typical 90 kg patient with PsA. Absolute SC bioavailability was estimated to be 83.5%. Exposure-response quartile analyses suggested that exposures associated with the clinical regimen maximized efficacy across the endpoints evaluated. No exposure dependency was observed for key safety endpoints.ConclusionsRisankizumab exhibited linear and time-independent pharmacokinetics in patients with PsA and was comparable to patients with plaque psoriasis. Efficacy and safety exposure-response analyses support that the clinical regimen achieved robust efficacy with a favorable safety profile for patients with active PsA.Clinical trialsNCT02596217, NCT02719171, NCT02986373, NCT03671148, and NCT03675308.Clinical trialsNCT02596217, NCT02719171, NCT02986373, NCT03671148, and NCT03675308.