Objective: To investigate the efficacy and safety of abatacept in combination with etanercept in patients with active rheumatoid arthritis during a 1-year, randomised, placebo-controlled, double-blind phase, followed by an open-label, long-term extension (LTE).
Methods: Patients continued etanercept (25 mg twice weekly) and were randomised to receive abatacept 2 mg/kg (n = 85) or placebo (n = 36). As the effective dose of abatacept was established as 10 mg/kg in a separate trial, all patients received abatacept 10 mg/kg and etanercept during the LTE.
Results: A total of 121 patients were randomised; 80 completed double-blind treatment and entered the LTE. During double-blind treatment, the difference in the percentage of patients achieving the primary end point (modified American College of Rheumatology (ACR) 20 response at 6 months) was not significant between groups (48.2% v 30.6%; p = 0.072). At 1 year, no notable changes in modified ACR responses were observed. Subsequent to the dosing change, similar modified ACR responses were seen during the LTE. Significant improvements in quality of life were observed with abatacept and etanercept versus placebo and etanercept in five of the eight short-form 36 subscales at 1 year. More abatacept and etanercept-treated patients experienced serious adverse events (SAEs) at 1 year than patients receiving placebo and etanercept (16.5% v 2.8%), with 3.5% v 0% experiencing serious infections.
Conclusion: The combination of abatacept (at a dose of 2 mg/kg during the double-blind phase and 10 mg/kg during the LTE) and etanercept was associated with an increase in SAEs, including serious infections, with limited clinical effect. On the basis of the limited efficacy findings and safety concerns, abatacept in combination with etanercept should not be used for rheumatoid arthritis treatment.
- ACR, American College of Rheumatology
- CRP, C reactive protein
- DMARD, disease-modifying antirheumatic drug
- LTE, long-term extension
- MCS, mental component summary
- MTX, methotrexate
- PCS, physical component summary
- SAE, serious adverse event
- SF-36, short-form 36
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Published Online First 25 August 2006
Funding: This study was funded and sponsored by Bristol-Myers Squibb, which was involved in the design of the study (conducted between 26 February 2001 and 22 June 2004), the collection and analysis of the data, the writing of the report and the decision to submit the report.
Competing interests: MW has received consulting fees (< US $10 000/year) from the sponsor of this study, Bristol-Myers Squibb, as a consultant. In addition, he has received research funding for support of this study. He has also received consulting fees (< US $10 000/year) from Wyeth, Amgen, Genentech, Centocor and Abbott and research funding from Amgen, Abbott and Genentech. MS has received research funding and consulting fees from Bristol-Myers Squibb, Abbott, Amgen, Wyeth and Centocor. JK has received research grants from Bristol-Myers Squibb and has also served as a consultant for research and on the development of educational presentations. AG and ML have no competing financial interests. TL is an employee of Bristol-Myers Squibb and owns Bristol-Myers Squibb stocks. DC and J-CB are both employees of Bristol-Myers Squibb.
Clinical investigators: The investigators for this study played a key role in its success. The following clinical investigators provided and cared for the study patients while participating in the study:
Drs Neal Birnbaum, San Francisco, California; Steven Carsons, Mineola, New York; Walter Chase, Austin, Texas; Melvin A Churchill, Lincoln, Nebraska; Stanley Cohen, Dallas, Texas; Geoffrey S Dolan, Long Beach, California; John Donahue, Boston, Massachusetts; Michael Ellman, Chicago, Illinois; Gary Fink, Charleston, South Carolina; Mark Genovese, Palo Alto, California; Allan Goldman, Milwaukee, Wisconsin; Richard Honsinger, Los Alamos, New Mexico; Christopher Jackson, Salt Lake City, Utah; Richard Jimenez, Edmonds, Washington; Alan Kivitz, Duncansville, Pennsylvania; Joel Kremer, Albany, New York; Robert Leff, Duluth, New Mexico; Michael Luggen, Cincinnati, Ohio; Raymond Malamet, Hagerstown, Maryland; Joseph Markenson, New York, New York; Daniel Norden, Norristown, Pennsylvania; David Pierangelo, Springfield, Massachusetts; Michael Schiff, Denver, Colorado; William Shergy, Huntsville, Alabama; Yvonne Sherrer, Ft Lauderdale, Florida; Lee Simon, Boston, Massachusetts; Nowarat Songsiridej, Bismarck, North Dakota; Elizabeth A Tindall, Portland, Oregon; Wayne Tsuji, Seattle, Washington; Daniel J Wallace, Los Angeles, California; Michael Weinblatt, Boston, Massachusetts; and David Wofsy, San Francisco, California.
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