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  • Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W)

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Spondyloarthritis
Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W)
  1. Maxime Dougados1,
  2. James Cheng-Chung Wei2,
  3. Robert Landewé3,
  4. Joachim Sieper4,
  5. Xenofon Baraliakos5,
  6. Filip Van den Bosch6,
  7. Walter P Maksymowych7,
  8. Joerg Ermann8,
  9. Jessica A Walsh9,
  10. Tetsuya Tomita10,
  11. Atul Deodhar11,
  12. Désirée van der Heijde12,
  13. Xiaoqi Li13,
  14. Fangyi Zhao13,
  15. Clinton C Bertram13,
  16. Gaia Gallo13,
  17. Hilde Carlier13,
  18. Lianne S Gensler14
  19. On behalf of COAST-V and COAST-W Study Groups
  1. 1 Paris Descartes University; Department of Rheumatology, Hôpital Cochin; Assistance Publique - Hôpitaux de Paris; INSERM (U1153), Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France
  2. 2 Institute of Medicine, Chung Shan Medical University; Department of Internal Medicine, Chung Shan Medical University Hospital; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
  3. 3 Amsterdam Rheumatology and Clinical Immunology Center, Amsterdam, The Netherlands
  4. 4 Charité Universitätsmedizin Berlin, Berlin, Germany
  5. 5 Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Bochum, Germany
  6. 6 Ghent University Hospital, Gent, Belgium
  7. 7 University of Alberta, Edmonton, Alberta, Canada
  8. 8 Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
  9. 9 Division of Rheumatology, University of Utah and Salt Lake City Veterans Affairs Medical Centers, Salt Lake City, Utah, USA
  10. 10 Department of Orthopaedic Biomaterial Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
  11. 11 Oregon Health and Science University, Portland, Oregon, USA
  12. 12 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  13. 13 Eli Lilly and Company, Indianapolis, Indiana, USA
  14. 14 University of California, San Francisco, California, USA
  1. Correspondence to Professor Maxime Dougados, Hopital Cochin, Rheumatology, Université Paris Descartes, Paris 75014, France; maxime.dougados{at}aphp.fr

Abstract

Objectives To investigate the efficacy and safety of ixekizumab for up to 52 weeks in two phase 3 studies of patients with active radiographic axial spondyloarthritis (r-axSpA) who were biological disease-modifying antirheumatic drug (bDMARD)-naive (COAST-V) or tumour necrosis factor inhibitor (TNFi)-experienced (COAST-W).

Methods Adults with active r-axSpA were randomised 1:1:1:1 (n=341) to 80 mg ixekizumab every 2 (IXE Q2W) or 4 weeks (IXE Q4W), placebo (PBO) or 40 mg adalimumab Q2W (ADA) in COAST-V and 1:1:1 (n=316) to IXE Q2W, IXE Q4W or PBO in COAST-W. At week 16, patients receiving ixekizumab continued their assigned treatment; patients receiving PBO or ADA were rerandomised 1:1 to IXE Q2W or IXE Q4W (PBO/IXE, ADA/IXE) through week 52.

Results In COAST-V, Assessment of SpondyloArthritis international Society 40 (ASAS40) responses rates (intent-to-treat population, non-responder imputation) at weeks 16 and 52 were 48% and 53% (IXE Q4W); 52% and 51% (IXE Q2W); 36% and 51% (ADA/IXE); 19% and 47% (PBO/IXE). Corresponding ASAS40 response rates in COAST-W were 25% and 34% (IXE Q4W); 31% and 31% (IXE Q2W); 14% and 39% (PBO/IXE). Both ixekizumab regimens sustained improvements in disease activity, physical function, objective markers of inflammation, QoL, health status and overall function up to 52 weeks. Safety through 52 weeks of ixekizumab was consistent with safety through 16 weeks.

Conclusion The significant efficacy demonstrated with ixekizumab at week 16 was sustained for up to 52 weeks in bDMARD-naive and TNFi-experienced patients. bDMARD-naive patients initially treated with ADA demonstrated further numerical improvements after switching to ixekizumab. Safety findings were consistent with the known safety profile of ixekizumab.

Trial registration number NCT02696785/NCT02696798.

  • ankylosing spondylitis
  • DMARDs (biologic)
  • spondyloarthritis
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/annrheumdis-2019-216118

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    Footnotes

    • Handling editor Josef S Smolen

    • Contributors All authors participated in the interpretation of study results, and in the drafting, critical revision and approval of the final version of the manuscript. MD, JC-CW, JS, FVdB, WPM, AD, DvdH, XL, FZ and HC contributed to study conception and/or design. JC-CW, RL, WPM, AD, DvdH, FZ, XL and HC contributed to the acquisition of study results. MD, RL, JS, XL, FZ and HC contributed to the analysis of study results.

    • Funding The studies described in this manuscript were sponsored by Eli Lilly and Company, which was involved in the study design, data collection, data analysis and preparation of the manuscript.

    • Competing interests MD has served as a consultant and received research grants from AbbVie, Eli Lilly and Company, Pfizer and UCB Pharma. JC-CW has served as a consultant and/or speaker and/or has received research grants from Abbott, Bristol-Myers Squibb, Celgene, Chugai, Eisai, Eli Lilly and Company, Janssen, Novartis, Pfizer, Sanofi-Aventis, TSH Taiwan and UCB Pharma. RL has served as a consultant and/or advisor and/or has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Galapagos, Merck, Novartis, Pfizer and UCB Pharma. RL is the director of Rheumatology Consultancy BV, a company that was indirectly contracted by Eli Lilly and Company to perform read services for the COAST program. JS has served as a consultant and/or speaker for AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche and UCB Pharma. XB has served as a consultant and/or has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Pfizer, Roche and UCB Pharma. FVdB has served as a consultant and/or speaker and/or has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Sanofi and UCB Pharma. WPM has served as a consultant and/or received honoraria and/or research/educational grants from AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma, and is Chief Medical Officer of CARE Arthritis Limited. JE has served as a consultant and/or received research grants from AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Novartis, Pfizer, Takeda and UCB Pharma. JAW has been a consultant and/or received research grants from AbbVie, Amgen, Celgene, Eli Lilly and Company, Novartis, Pfizer and UCB Pharma. AD has been a consultant and/or received research support from AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, Glaxo Smith & Klein, Janssen, Novartis, Pfizer and UCB Pharma. DvdH has been a consultant for AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly and Company, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB Pharma and is a Director of Imaging Rheumatology BV. TT has been a consultant and speaker for AbbVie, Astellas, Bristol-Myers Squibb, Eisai, Eli Lilly and Company, Janssen, Mitsubishi Tanabe, Novartis, Pfizer and Takeda. XL, FZ, CCB, GG and HC are current employees and shareholders of Eli Lilly and Company. LSG has been a consultant and/or received research grants/support from AbbVie, Amgen, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma.

    • Patient consent for publication Not required.

    • Ethics approval Trial protocols were approved by ethics review boards at each study site. Trials were performed in accordance with the ethical principles of the Declaration of Helsinki.

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

    • Data availability statement Lilly provides access to all individual participant data collected during the trial, after anonymisation, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the United States and the European Union and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once they are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank or annotated case report forms, will be provided in a secure data sharing environment for up to 2 years per proposal. For details on submitting a request, see the instructions provided at www.clinicalstudydatarequest.com.