Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study

Dominique Baeten, Mikkel Østergaard, James Cheng-Chung Wei, Joachim Sieper, Pentti Järvinen, Lai-Shan Tam, Carlo Salvarani, Tae-Hwan Kim, Alan Solinger, Yakov Datsenko, Chandrasena Pamulapati, Sudha Visvanathan, David B Hall, Stella Aslanyan, Paul Scholl, Steven J Padula

137 Citations (Scopus)
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Abstract

OBJECTIVES: To evaluate the efficacy and safety of risankizumab, a humanised monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), in patients with active ankylosing spondylitis (AS).

METHODS: A total of 159 patients with biological-naïve AS, with active disease (Bath Ankylosing Spondylitis Disease Activity Index score of ≥4), were randomised (1:1:1:1) to risankizumab (18 mg single dose, 90 mg or 180 mg at day 1 and weeks 8, 16 and 24) or placebo over a 24-week blinded period. The primary outcome was a 40% improvement in Assessment in Spondylo Arthritis International Society (ASAS40) at week 12. Safety was assessed in patients who received at least one dose of study drug.

RESULTS: At week 12, ASAS40 response rates were 25.5%, 20.5% and 15.0% in the 18 mg, 90 mg and 180 mg risankizumab groups, respectively, compared with 17.5% in the placebo group. The estimated difference in proportion between the 180 mg risankizumab and placebo groups (primary endpoint) was -2.5% (95% CI -21.8 to 17.0; p=0.42). Rates of adverse events were similar in all treatment groups.

CONCLUSIONS: Treatment with risankizumab did not meet the study primary endpoint and showed no evidence of clinically meaningful improvements compared with placebo in patients with active AS, suggesting that IL-23 may not be a relevant driver of disease pathogenesis and symptoms in AS.

TRIAL REGISTRATION NUMBER: NCT02047110; Pre-results.

Original languageEnglish
JournalAnnals of the Rheumatic Diseases
Volume77
Issue number9
Pages (from-to)1295-1302
Number of pages8
ISSN0003-4967
DOIs
Publication statusPublished - 1 Sept 2018

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