TY - JOUR
T1 - Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: Results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study
AU - Baeten, Dominique
AU - Østergaard, Mikkel
AU - Wei, James Cheng-Chung
AU - Sieper, Joachim
AU - Järvinen, Pentti
AU - Tam, Lai-Shan
AU - Salvarani, Carlo
AU - Kim, Tae-Hwan
AU - Solinger, Alan
AU - Datsenko, Yakov
AU - Pamulapati, Chandrasena
AU - Visvanathan, Sudha
AU - Hall, David B.
AU - Aslanyan, Stella
AU - Scholl, Paul
AU - Padula, Steven J.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85049171519&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29945918
U2 - https://doi.org/10.1136/annrheumdis-2018-213328
DO - https://doi.org/10.1136/annrheumdis-2018-213328
M3 - Article
C2 - 29945918
SN - 0003-4967
VL - 77
SP - 1295
EP - 1302
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 9
ER -