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Extended report
Efficacy and safety of abatacept, a T-cell modulator, in a randomised, double-blind, placebo-controlled, phase III study in psoriatic arthritis
  1. Philip J Mease1,
  2. Alice B Gottlieb2,
  3. Désirée van der Heijde3,
  4. Oliver FitzGerald4,
  5. Alyssa Johnsen5,
  6. Marleen Nys6,
  7. Subhashis Banerjee5,
  8. Dafna D Gladman7
  1. 1 Swedish Medical Center and University of Washington, Seattle, Washington, USA
  2. 2 New York Medical College, Valhalla, New York, USA
  3. 3 Leiden University Medical Center, Leiden, Netherlands
  4. 4 St Vincent’s University Hospital and University College Dublin, Dublin, Ireland
  5. 5 Bristol-Myers Squibb, Princeton, New Jersey, USA
  6. 6 Bristol-Myers Squibb, Braine-l’Alleud, Belgium
  7. 7 University of Toronto and Toronto Western Hospital, Toronto, Canada
  1. Correspondence to Dr Philip J Mease, Swedish Medical Center and University of Washington, Seattle Rheumatology Associates, 601 Broadway, Suite 600, Seattle, WA 98122, USA; pmease{at}philipmease.com

Abstract

Objectives To assess the efficacy and safety of abatacept, a selective T-cell costimulation modulator, in a phase III study in psoriatic arthritis (PsA).

Methods This study randomised patients (1:1) with active PsA (~60% with prior exposure to a tumour necrosis factor inhibitor) to blinded weekly subcutaneous abatacept 125 mg (n=213) or placebo (n=211) for 24 weeks, followed by open-label subcutaneous abatacept. Patients without ≥20% improvement in joint counts at week 16 were switched to open-label abatacept. The primary end point was the proportion of patients with ≥20% improvement in the American College of Rheumatology (ACR20) criteria at week 24.

Results Abatacept significantly increased ACR20 response versus placebo at week 24 (39.4% vs 22.3%; p<0.001). Although abatacept numerically increased Health Assessment Questionnaire–Disability Index response rates (reduction from baseline ≥0.35) at week 24, this was not statistically significant (31.0% vs 23.7%; p=0.097). The benefits of abatacept were seen in ACR20 responses regardless of tumour necrosis factor inhibitor exposure and in other musculoskeletal manifestations, but significance could not be attributed due to ranking below Health Assessment Questionnaire–Disability Index response in hierarchical testing. However, the benefit on psoriasis lesions was modest. Efficacy was maintained or improved up to week 52. Abatacept was well tolerated with no new safety signals.

Conclusions Abatacept treatment of PsA in this phase III study achieved its primary end point, ACR20 response, showed beneficial trends overall in musculoskeletal manifestations and was well tolerated. There was only a modest impact on psoriasis lesions.

Trial registration number ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb).

  • Psoriatic arthritis
  • DMARDs (biologic)
  • T cells
  • Treatment

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Footnotes

  • Contributors PM, ABG and DG were involved in the conception and design of the study and interpretation of data. DvdH and MN were involved in the conception and design of the study, acquisition of data and interpretation of data. OF was involved in interpretation of data. SB was involved in the acquisition of data and the analysis and interpretation of data. AJ was involved in the conception and design of the study, acquisition of data and the analysis and interpretation of data. All authors had full access to the study data, critically reviewed the manuscript and approved the final version prior to submission and take responsibility for the integrity and accuracy of the reported data.

  • Funding This study was funded by Bristol-Myers Squibb. Under the direction of the authors, Sharon Gladwin of Caudex, Oxford, UK (funded by Bristol-Myers Squibb) provided writing assistance for the development of this manuscript. Editorial assistance was provided by Paul Wilmott of Caudex, funded by Bristol-Myers Squibb. Sandra Overfield, Protocol Manager, Bristol-Myers Squibb assisted in initial design and operational aspects of the study.

  • Competing interests PM reports receiving consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Crescendo, Demira, Janssen, Lilly, Merck, Novartis, Pfizer, Sun, UCB and Zynerba; and speaker fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Novartis, Pfizer and UCB. ABG reports receiving consulting fees from Abbott Laboratories (AbbVie), Actelion, Akros, Amgen, Astellas, Baxalta, Beiersdorf, Bristol-Myers Squibb, Canfite, Catabasis, Celgene, Centocor (Janssen), Coronado, CSL Behring Biotherapies for Life, Dermipsor, Genentech, GlaxoSmithKline, Incyte, Karyopharm, Kineta One, KPI Therapeutics, Lilly, Meiji Seika Pharma, Mitsubishi Tanabe Pharma Development America, Novartis, Novo Nordisk, Pfizer, Takeda, TEVA, UCB, Vertex and Xenoport; and research grants (paid to Tufts Medical Center) from Abbott Laboratories (AbbVie), Amgen, Baxalta, Celgene, Centocor (Janssen), Dermira, Levia, Lilly, Merck, Novartis, Pfizer and Xenoport. DvdH reports receiving consultancy fees from Bristol-Myers Squibb and also consultancy fees from AbbVie, Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB (outside the submitted work). OF reports receiving grant support from AbbVie, Bristol-Myers Squibb and Pfizer; and speaker fees from Celgene, Janssen, Novartis and UCB. AJ is an employee of Bristol-Myers Squibb and reports holding stock in Bristol-Myers Squibb. MN is an employee of Bristol-Myers Squibb. SB is an employee of Bristol-Myers Squibb and reports holding stock in Bristol-Myers Squibb. DG reports receiving grant support from Bristol-Myers Squibb to participate in this study; in addition, she reports receiving grant support and fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB.

  • Ethics approval Schulman Associates Institutional Review Board.

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

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