ARTHRITIS & RHEUMATISM Vol. 52, No. 8, August 2005, pp 2263–2271 DOI 10.1002/art.21201 © 2005, American College of Rheumatology Treatment of Rheumatoid Arthritis With the Selective Costimulation Modulator Abatacept Twelve-Month Results of a Phase IIb, Double-Blind, Randomized, Placebo-Controlled Trial Joel M. Kremer, 1 Maxime Dougados, 2 Paul Emery, 3 Patrick Durez, 4 Jean Sibilia, 5 William Shergy, 6 Serge Steinfeld, 7 Elizabeth Tindall, 8 Jean-Claude Becker, 9 Tracy Li, 9 Isaac F. Nuamah, 9 Richard Aranda, 9 and Larry W. Moreland 10 Objective. To determine the clinical efficacy, safety, and immunogenicity of abatacept (CTLA-4Ig), a selective costimulation modulator, in patients with rheumatoid arthritis (RA) that has remained active despite methotrexate (MTX) therapy. Methods. This was a 12-month, multicenter, ran- domized, double-blind, placebo-controlled study. A total of 339 patients with active RA despite MTX therapy were randomly assigned to receive 10 mg/kg abatacept (n  115), 2 mg/kg abatacept (n  105), or placebo (n  119). This report focuses on the results observed at month 12 of a phase IIb trial. Results. A significantly greater percentage of pa- tients treated with 10 mg/kg abatacept met the Ameri- can College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at 1 year compared with patients who received placebo (62.6% versus 36.1%; P < 0.001). Greater percentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7% versus 20.2%; P < 0.001) and ACR70 responses (20.9% versus 7.6%; P  0.003) compared with patients who received placebo. For patients treated with 10 mg/kg abatacept, there were also statistically significant and clinically important improvements in modified Health Assessment Questionnaire scores compared with pa- tients who received placebo (49.6% versus 27.7%; P < 0.001). Abatacept at a dosage of 10 mg/kg elicited an increase in rates of remission (Disease Activity Score in 28 joints of <2.6) compared with placebo at 1 year (34.8% versus 10.1%; P < 0.001). The incidence of adverse events was comparable between the groups, and no significant formation of neutralizing antibodies was noted. Conclusion. Abatacept was associated with signif- icant reductions in disease activity and improvements in physical function that were maintained over the course of 12 months in patients with RA that had remained active despite MTX treatment. Abatacept was found to be well tolerated and safe over the course of 1 year. Abatacept in combination with MTX has the potential to play an important role in future RA therapy. Rheumatoid arthritis (RA) is a complex auto- immune disease that may lead to joint destruction, disability, and poor quality of life (QOL). While exper- imental models of RA pathogenesis show that multiple pathways and cell types are involved (1–3), there is Supported by a grant from Bristol-Myers Squibb. 1 Joel M. Kremer, MD: Center for Rheumatology, Albany, New York; 2 Maxime Dougados, MD: Rene Descartes University, Ho ˆpital Cochin Assistance Publique–Ho ˆpitaux de Paris, Paris, France; 3 Paul Emery, MD: Leeds General Infirmary, Leeds, UK; 4 Patrick Durez, MD: Cliniques Universitaires Saint-Luc, Universite ´ Catholique de Louvain, Brussels, Belgium; 5 Jean Sibilia, MD, PhD: Centre Hospitalier Universitaire, Louis Pasteur University, Strasbourg, France; 6 William Shergy, MD: Rheumatology Associates of North Alabama, Huntsville; 7 Serge Steinfeld, MD: Erasme University Hos- pital, Brussels, Belgium; 8 Elizabeth Tindall, MD: Oregon Health and Science University, Portland; 9 Jean-Claude Becker, MD, Tracy Li, PhD, Isaac F. Nuamah, PhD, Richard Aranda, MD: Bristol-Myers Squibb, Princeton, New Jersey; 10 Larry W. Moreland, MD: University of Alabama at Birmingham School of Medicine. Drs. Kremer, Steinfeld, and Nuamah have received consulting fees of less than $10,000 from Bristol-Myers Squibb. Address correspondence and reprint requests to Joel M. Kremer, MD, Center for Rheumatology, 1367 Washington Avenue, Suite 1, Albany, NY 12206. E-mail: jkremer@joint-docs.com. Submitted for publication September 28, 2004; accepted in revised form April 25, 2005. 2263