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Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study
  1. Dominique Baeten1,
  2. Mikkel Østergaard2,3,
  3. James Cheng-Chung Wei4,5,
  4. Joachim Sieper6,
  5. Pentti Järvinen7,
  6. Lai-Shan Tam8,
  7. Carlo Salvarani9,10,
  8. Tae-Hwan Kim11,
  9. Alan Solinger12,
  10. Yakov Datsenko13,
  11. Chandrasena Pamulapati12,
  12. Sudha Visvanathan12,
  13. David B Hall12,
  14. Stella Aslanyan12,
  15. Paul Scholl12,
  16. Steven J Padula14
  1. 1 Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  2. 2 Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark
  3. 3 Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
  4. 4 Department of Internal Medicine, Institute of Medicine, Chung Shan Medical University, Chung Shan Medical University Hospital, Taichung, Taiwan
  5. 5 Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
  6. 6 Medical Department I, Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany
  7. 7 Kiljavan Lääketutkimus Oy, Hyvinkää, Finland
  8. 8 Department of Medicine and Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
  9. 9 Rheumatology Unit, Azienda Ospedaliera-IRCCS di Reggio Emilia, Reggio Emilia, Italy
  10. 10 Università di Modena e Reggio Emilia, Modena, Italy
  11. 11 Department of Rheumatology, Hanyang University Hospital, Seoul, The Republic of Korea
  12. 12 Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA
  13. 13 Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
  14. 14 Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany
  1. Correspondence to Dr James Cheng-Chung Wei, Department of Internal Medicine, Institute of Medicine, Chung Shan Medical University, Chung Shan Medical University Hospital, Taichung 402, Taiwan; wei3228{at}gmail.com

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.

  • ankylosing spondylitis
  • DMARDs (biologic)
  • treatment

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors DB, DBH, MØ, SJP and PS contributed to study design. DB, PJ, T-HK, MØ, AS, CS, JS, L-ST and JC-CW contributed to data collection. All authors had full access to the study data, contributed to data analysis, data interpretation, writing and review of the manuscript and approved the final version for publication.

  • Funding This study was funded by Boehringer Ingelheim. Editorial assistance in the development of this manuscript was provided by Leigh Church of SuccinctChoice Medical Communications (London, UK), funded by Boehringer Ingelheim.

  • Competing interests DB reports grants from AbbVie, Pfizer, UCB, MSD, Novartis and Eli Lilly and part-time employment at UCB. MØ reports grants, personal fees and non-financial support from AbbVie, BMS, Merck, UCB and Novartis; grants and personal fees from Celgene; personal fees and non-financial support from Janssen, Pfizer and Roche; and personal fees from Boehringer Ingelheim, Eli Lilly, Sanofi, Regeneron, Orion and Hospira. JS reports personal fees from Boehringer Ingelheim, AbbVie, Janssen, Lilly, Merck, Novartis, Pfizer and UCB. PJ reports grants from AbbVie, Daiichi Sankyo, Boehringer Ingelheim, Lilly, Novartis, Roche and UCB and grants and personal fees from BMS and Pfizer. YD, CP, SV, DBH, SA, PS and SJP report being employees of Boehringer Ingelheim.

  • Patient consent Not required.

  • Ethics approval The study protocol was approved by the institutional review board or ethics committee at each participating centre. The study was conducted according to the Declaration of Helsinki and the International Conference on Harmonisation guidelines. Safety data were periodically evaluated by an independent data monitoring committee. All patients provided written informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The authors confirm that the data supporting the findings of this study are available within the article or its supplementary materials.

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