Three Multicenter, Randomized, Double-Blind, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Ustekinumab in Axial Spondyloarthritis.

Author(s): Deodhar, A; Gensler, LS; Sieper, J; Clark, M; Calderon, C; Wang, Y; Zhou, Y; Leu, JH; Campbell, K; Sweet, K; Harrison, DD; Hsia, EC; van der Heijde, D | Abstract: The efficacy and safety of ustekinumab were evaluated in 3 randomized, placebo-controlled studies in patients with axial spondyloarthritis (axSpA). The first 2 studies included patients with radiographic axSpA (Study 1 [anti-tumor necrosis factor (TNF)-naive]; Study 2 [anti-TNF refractory]), and Study 3 patients had non-radiographic axSpA.In all 3 studies, patients were randomly assigned (1:1:1) to receive subcutaneous ustekinumab 45mg or 90mg or placebo up to 24 weeks, after which placebo-treated patients were rerandomized to receive ustekinumab 45mg or 90mg. The primary endpoint in Studies 1 and 2 was 40% improvement on Assessment of SpondyloArthritis international Society (ASAS40); for Study 3, it was 20% ASAS improvement (ASAS20). Other disease activity and safety measures were also evaluated. A Week 24 analysis of Study 1 was pre-planned to determine continuation of Studies 2 and 3.For Study 1, primary and major secondary endpoints were not met, and the study was discontinued. As a result, Studies 2 and 3 were prematurely discontinued before they were fully enrolled. For all 3 studies, neither ustekinumab dose group demonstrated clinically meaningful improvement over placebo on key efficacy endpoints. The proportion of patients experiencing adverse events in the ustekinumab groups was consistent with those in previous studies.In these 3 placebo-controlled trials, efficacy of ustekinumab in the treatment of axSpA was not demonstrated. The safety profile was consistent with that of studies in other indications. This article is protected by copyright. All rights reserved.