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

Ann Rheum Dis. 2018 Sep;77(9):1295-1302. doi: 10.1136/annrheumdis-2018-213328. Epub 2018 Jun 26.

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.

Keywords: DMARDs (biologic); ankylosing spondylitis; treatment.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin-23 Subunit p19 / antagonists & inhibitors
  • Male
  • Middle Aged
  • Proof of Concept Study
  • Remission Induction
  • Severity of Illness Index
  • Spondylitis, Ankylosing / drug therapy*
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Interleukin-23 Subunit p19
  • risankizumab

Associated data

  • ClinicalTrials.gov/NCT02047110