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Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve to biological disease-modifying antirheumatic drug: final results by week 52
  1. Josef S Smolen1,
  2. Philip Mease2,3,
  3. Hasan Tahir4,
  4. Hendrik Schulze-Koops5,
  5. Inmaculada de la Torre6,
  6. Lingnan Li6,
  7. Maja Hojnik6,
  8. Christophe Sapin6,
  9. Masato Okada7,
  10. Roberto Caporali8,
  11. Jordi Gratacós9,
  12. Philippe Goupille10,
  13. Soyi Liu Leage6,
  14. Sreekumar Pillai6,
  15. Peter Nash11
  1. 1 Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
  2. 2 Providence St Joseph Health, Rentton, Washington, USA
  3. 3 Swedish Medical Center, Seattle, Washington, USA
  4. 4 Royal Free London NHS Foundation Trust, London, UK
  5. 5 Division of Rheumatology and Clinical Immunology, Department of Internal Medicine IV, Ludwig Maximilians University Munich, Munich, Germany
  6. 6 Eli Lilly and Company, Indianapolis, Indiana, USA
  7. 7 Immuno-Rheumatology Center, St. Luke’s International Hospital, Tokyo, Japan
  8. 8 Department of Clinical Sciences and Community Health, University of Milan, G. Pini Hospital, Milan, Lombardia, Italy
  9. 9 Rheumatology Department, Hospital Universitario Parc Taulí, Barcelona, Spain
  10. 10 Department of Rheumatology, Regional University Hospital Centre Tours, Tours, Centre, France
  11. 11 Griffith University School of Medicine, Gold Coast, Queensland, Australia
  1. Correspondence to Dr Josef S Smolen, Medical University of Vienna, Vienna, Austria; josef.smolen{at}meduniwien.ac.at

Abstract

Objectives SPIRIT head-to-head (H2H) is a 52-week (Wk) trial comparing ixekizumab (IXE) with adalimumab (ADA) for simultaneous American College of Rheumatology (ACR)50 and Psoriasis Area and Severity Index (PASI)100 responses in 566 patients (distributed evenly across both groups) with psoriatic arthritis (PsA). IXE was superior to ADA for this primary end point at Wk24. We aimed to determine the final efficacy and safety results through Wk52 including a prespecified subgroup analysis of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) use.

Methods SPIRIT-H2H is a Wk52 multicentre, open-label, blinded-assessor study comparing IXE and ADA in bionaïve patients with PsA. Patients were randomised 1:1 to IXE or ADA with stratification by concomitant csDMARD use and presence of moderate-to-severe plaque psoriasis. Prespecified end points at Wk24 and Wk52 included musculoskeletal, psoriasis, quality-of life outcomes, subgroup analyses and safety.

Results A significantly higher proportion of patients treated with IXE versus ADA simultaneously achieved ACR50 and PASI100 (39% vs 26%, p<0.001), PASI100 (64% vs 41%, p<0.001) at Wk52. Efficacy of IXE and ADA was similar at Wk52 for ACR50 (49.8% vs 49.8%, p=0.924), treat-to-target outcomes, enthesitis and dactylitis resolution. Responses to IXE were consistent irrespective of concomitant csDMARD use. Significantly more patients on IXE monotherapy versus ADA monotherapy had simultaneous ACR50 and PASI100 (38% vs 19%, p=0.007), and PASI100 responses (66% vs 35%, p<0.001) at Wk52. There were no new safety findings for IXE or ADA.

Conclusions IXE provided significantly greater simultaneous joint and skin improvement than ADA through Wk52 in bionaïve patients with PsA. IXE showed better efficacy on psoriasis and performed at least as well as ADA on musculoskeletal manifestations. IXE efficacy was consistent irrespective of concomitant csDMARD use.

Trial registration number NCT03151551.

  • inflammation
  • arthritis, psoriatic
  • adalimumab
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Footnotes

  • Handling editor David S Pisetsky

  • Correction notice This article has been corrected since it published Online First. The footnote symbol for Crohn's disease in table 3 has been corrected.

  • Contributors All authors contributed to critical revision of the manuscript and gave final approval for submission and publication. JS, PN and PM provided advice on additional analysis to be performed and interpretation of the data. HT, HS-K, MO, RC, JG and PG contributed to the interpretation of the data. SLL contributed to study conception, data acquisition and interruption. SP, LL, MH, CS and IdlT contributed to data acquisition and interruption.

  • Funding This study was funded by Eli Lilly and Company, which contributed to study design, data collection, data analysis, data interpretation, manuscript preparation and publication decisions.

  • Competing interests JSS received grants to his institution from AbbVie, AstraZeneca, Eli Lilly and Company, Merck Sharpe & Dohme, Pfizer and Roche and provided expert advice for, or had symposia speaking engagements with, AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO Pharma, Janssen, Lilly, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi and UCB. PM has received research grants from AbbVie, Amgen, Bristol Myers Squibb, Janssen, Eli Lilly and Company, Novartis, Pfizer, Sun, UCB, has performed consultation for AbbVie, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli Lilly and Company, Novartis, Pfizer, Sun, UCB and a speaker for AbbVie, Amgen, Janssen, Eli Lilly and Company, Novartis, Pfizer, UCBHT has performed consultation for Novartis, Eli Lilly and Company, AbbVie. HS-K has performed consultation for AbbVie, Amgen, Mylan, Sandoz-Hexal, Eli Lilly and Company. IdlT is a full-time employee and shareholder of Eli Lilly and Company. LL is a full-time employee of Eli Lilly and Company. MH is a full-time employee of Eli Lilly and Company. CS is a full-time employee and shareholder of Eli Lilly and Company. MO is an Honoraria of Eli Lilly and Company and Astellas. RC is a member of speakers’ bureau for AbbVie, Amgen, Pfizer, Eli Lilly and Company, MSD, UCB, Gilead, BMS, Sanofi. JG has received fees for participating in Advisory Boards or conferences from AbbVie, Novartis, Pfizer, Amjen, Eli Lilly and Company, MSD, Celgene, Zanofi and Roche. PG has received research grants, consultation fees or speaker honoraria from AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Eil Lilly and Company, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB. SL-L is an employee and shareholder of Eli Lilly and Company. SP is a full-time employee of Eli Lilly and Company. PN has received grants for research and clinical trials and honoraria for advice and lectures on behalf Eli Lilly and Company, BMS, UCB, Sanofi, Roche, Novartis, Pfizer, AbbVie, MSD, Celgene, Gilead, Janssen.

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval SPIRIT-H2H was conducted in accordance with the ethical principles of the Declaration of Helsinki. All patients provided written informed consent, and the study protocol was approved by the ethical review board prior to the start of study-related procedures.

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

  • Data availability statement Data may be obtained from a third party and are not publicly available. Eli Lilly and Company provides access to relevant anonymised patient-level data from studies on approved medicines and indications as defined by the sponsor-specific information at www.clinicalstudydatarequest.com. Additional study-related documents will be made available, including the study protocol, statistical analysis plan, clinical study report and an annotated case report form. These materials will be available beginning 6 months after the publication is accepted, given approval of the indication in the USA and EU. These materials will be provided to achieve the aims in the provided proposal.

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