Risankizumab, an IL-23 Inhibitor, for Ankylosing Spondylitis: Results of a Randomised, Double-blind, Placebo-controlled, Proof-of-concept, Dose-finding Phase 2 Study

Overview

Journal Ann Rheum Dis

Specialty Rheumatology

Date 2018 Jun 28

PMID 29945918

Citations 147

Authors

Dominique Baeten

Mikkel Ostergaard

James Cheng-Chung Wei

Joachim Sieper

Pentti Jarvinen

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

Affiliations

Soon will be listed here.

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.

Citing Articles

The Causal Relationships and Therapeutic Targets of Plasma Proteins in Ankylosing Spondylitis.

Wen P, Yang M, Wang Y, Niu Y, Yang P, Hu S Biomedicines. 2025; 13(2).

PMID: 40002719 PMC: 11853591. DOI: 10.3390/biomedicines13020306.

Risankizumab and Certolizumab Pegol Dual-Targeted Therapy for Crohn's Disease and Axial Spondyloarthritis: A Case Report.

Lehmann A, Vosbeck J, Kyburz D, Hruz P, Hendrik Niess J Case Rep Gastroenterol. 2025; 19(1):22-30.

PMID: 39981170 PMC: 11668535. DOI: 10.1159/000542759.

The Spondyloarthritides: From Scientific and Therapeutic Immobility to the Forefront of Rheumatology Research.

Fragoulis G, Papagoras C Mediterr J Rheumatol. 2025; 35(Suppl 3):510-512.

PMID: 39974591 PMC: 11834992. DOI: 10.31138/mjr.121224.sat.

TNFα Inhibitors Versus Newer Therapies in Spondyloarthritis: Where do we Stand Today?.

Drosos A, Pelechas E, Venetsanopoulou A, Voulgari P Mediterr J Rheumatol. 2025; 35(Suppl 3):519-527.

PMID: 39974590 PMC: 11834995. DOI: 10.31138/mjr.040224.tvn.

Fast, Present and Future of the Concept of Spondyloarthritis.

Braun J Curr Rheumatol Rep. 2025; 27(1):15.

PMID: 39869233 DOI: 10.1007/s11926-024-01179-0.

References

Baraliakos X, Borah B, Braun J, Baeten D, Laurent D, Sieper J . Long-term effects of secukinumab on MRI findings in relation to clinical efficacy in subjects with active ankylosing spondylitis: an observational study. Ann Rheum Dis. 2015; 75(2):408-12. DOI: 10.1136/annrheumdis-2015-207544. View

Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P . Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med. 2015; 373(26):2534-48. DOI: 10.1056/NEJMoa1505066. View

Reveille J, Sims A, Danoy P, Evans D, Leo P, Pointon J . Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet. 2010; 42(2):123-7. PMC: 3224997. DOI: 10.1038/ng.513. View

Sarin R, Wu X, Abraham C . Inflammatory disease protective R381Q IL23 receptor polymorphism results in decreased primary CD4+ and CD8+ human T-cell functional responses. Proc Natl Acad Sci U S A. 2011; 108(23):9560-5. PMC: 3111257. DOI: 10.1073/pnas.1017854108. View

Zeng L, Lindstrom M, Smith J . Ankylosing spondylitis macrophage production of higher levels of interleukin-23 in response to lipopolysaccharide without induction of a significant unfolded protein response. Arthritis Rheum. 2011; 63(12):3807-17. PMC: 3228355. DOI: 10.1002/art.30593. View

van der Heijde D, Ramiro S, Landewe R, Baraliakos X, Van den Bosch F, Sepriano A . 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017; 76(6):978-991. DOI: 10.1136/annrheumdis-2016-210770. View

van der Linden S, VALKENBURG H, Cats A . Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984; 27(4):361-8. DOI: 10.1002/art.1780270401. View

Zhang L, Li Y, Li Y, Qi L, Liu X, Yuan C . Increased frequencies of Th22 cells as well as Th17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis. PLoS One. 2012; 7(4):e31000. PMC: 3317658. DOI: 10.1371/journal.pone.0031000. View

Poddubnyy D, Hermann K, Callhoff J, Listing J, Sieper J . Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS). Ann Rheum Dis. 2014; 73(5):817-23. DOI: 10.1136/annrheumdis-2013-204248. View

10.

Ward M, Deodhar A, Akl E, Lui A, Ermann J, Gensler L . American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2015; 68(2):282-98. PMC: 5123840. DOI: 10.1002/art.39298. View

11.

Papp K, Blauvelt A, Bukhalo M, Gooderham M, Krueger J, Lacour J . Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis. N Engl J Med. 2017; 376(16):1551-1560. DOI: 10.1056/NEJMoa1607017. View

12.

Gracey E, Qaiyum Z, Almaghlouth I, Lawson D, Karki S, Avvaru N . IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis. Ann Rheum Dis. 2016; 75(12):2124-2132. DOI: 10.1136/annrheumdis-2015-208902. View

13.

Mangan P, Su L, Jenny V, Tatum A, Picarillo C, Skala S . Dual Inhibition of Interleukin-23 and Interleukin-17 Offers Superior Efficacy in Mouse Models of Autoimmunity. J Pharmacol Exp Ther. 2015; 354(2):152-65. DOI: 10.1124/jpet.115.224246. View

14.

Sherlock J, Joyce-Shaikh B, Turner S, Chao C, Sathe M, Grein J . IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4-CD8- entheseal resident T cells. Nat Med. 2012; 18(7):1069-76. DOI: 10.1038/nm.2817. View

15.

Singh S, Kroe-Barrett R, Canada K, Zhu X, Sepulveda E, Wu H . Selective targeting of the IL23 pathway: Generation and characterization of a novel high-affinity humanized anti-IL23A antibody. MAbs. 2015; 7(4):778-91. PMC: 4622456. DOI: 10.1080/19420862.2015.1032491. View

16.

Dougados M, Baeten D . Spondyloarthritis. Lancet. 2011; 377(9783):2127-37. DOI: 10.1016/S0140-6736(11)60071-8. View

17.

Krueger J, Ferris L, Menter A, Wagner F, White A, Visvanathan S . Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2015; 136(1):116-124.e7. DOI: 10.1016/j.jaci.2015.01.018. View

18.

Benham H, Rehaume L, Hasnain S, Velasco J, Baillet A, Ruutu M . Interleukin-23 mediates the intestinal response to microbial β-1,3-glucan and the development of spondyloarthritis pathology in SKG mice. Arthritis Rheumatol. 2014; 66(7):1755-67. DOI: 10.1002/art.38638. View

19.

Appel H, Maier R, Bleil J, Hempfing A, Loddenkemper C, Schlichting U . In situ analysis of interleukin-23- and interleukin-12-positive cells in the spine of patients with ankylosing spondylitis. Arthritis Rheum. 2013; 65(6):1522-9. DOI: 10.1002/art.37937. View

20.

Feagan B, Sandborn W, DHaens G, Panes J, Kaser A, Ferrante M . Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2017; 389(10080):1699-1709. DOI: 10.1016/S0140-6736(17)30570-6. View