Extended report 1 Denver Arthritis Clinic, Denver, Colorado, USA; 2 Pontificial Catholic University, School of Medicine, Porto Alegre, Brazil; 3 Health Research of Oklahoma, Oklahoma City, Oklahoma, USA; 4 Arthritis & Osteoporosis Center, Flowood, Missouri, USA; 5 Centro Medico Privado De Reumatologia, Tucuman, Argentina; 6 St Augustine’s Hospital, Durban, South Africa; 7 Centro de Investigacion del Noroeste, Tijuana, Mexico; 8 Bristol-Myers Squibb, Princeton, New Jersey, USA; 9 Bristol-Myers Squibb, Pennington, New Jersey, USA; 10 Paris-Descartes University, Medicine Faculty and UPRES-EA 4058; AP-HP, Cochin Hospital; Paris, France Correspondence to: Dr M Schiff, Denver Arthritis Clinic, 200 Spruce Street #100, Denver, CO 80230, USA; Lmschiff@aol.com Accepted 17 November 2007 Published Online First 29 November 2007 This paper is freely available online under the BMJ Journals unlocked scheme, see http:// ard.bmj.com/info/unlocked.dtl 1096 Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate M Schiff,1 M Keiserman,2 C Codding,3 S Songcharoen,4 A Berman,5 S Nayiager,6 C Saldate,7 T Li,8 R Aranda,8 J-C Becker,8 C Lin,9 P L N Cornet,8 M Dougados10 ABSTRACT Objectives: This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo. The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score (based on erythrocyte sedimentation rates; DAS28 (ESR)) for the abatacept vs placebo groups at day 197. Methods: Patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) were randomised 3:3:2 to abatacept (,10 mg/kg every 4 weeks, n = 156), infliximab (3 mg/kg every 8 weeks, n = 165), or placebo (every 4 weeks, n = 110) and background MTX. Safety and efficacy were assessed throughout the study. Results: Similar patient demographics and clinical characteristics were present at baseline between groups, with mean scores of ,1.7 for HAQ-DI and 6.8 for DAS28 (ESR). At 6 months, mean changes in DAS28 (ESR) were significantly greater for abatacept vs placebo (–2.53 vs –1.48, p,0.001) and infliximab vs placebo (–2.25 vs –1.48, p,0.001). For abatacept vs infliximab treatment at day 365, reductions in the DAS28 (ESR) were –2.88 vs –2.25. At day 365, the following response rates were observed for abatacept and infliximab, respectively: American College of Rheumatology (ACR) 20, 72.4 and 55.8%; ACR 50, 45.5 and 36.4%; ACR 70, 26.3 and 20.6%; low disease activity score (LDAS), 35.3 and 22.4%; DAS28-defined remission, 18.7 and 12.2%; good European League Against Rheumatism (EULAR) responses, 32.0 and 18.5%; and Health Assessment Questionnaire Disability Index (HAQ-DI), 57.7 and 52.7%. Mean changes in physical component summary (PCS) were 9.5 and 7.6, and mental component summary (MCS) were 6.0 and 4.0, for abatacept and infliximab, respectively. Over 1 year, adverse events (AEs) (89.1 vs 93.3%), serious AEs (SAEs) (9.6 vs 18.2%), serious infections (1.9 vs 8.5%) and discontinuations due to AEs (3.2 vs 7.3%) and SAEs (2.6 vs 3.6%) were lower with abatacept than infliximab. Conclusions: In this study, abatacept and infliximab (3 mg/kg every 8 weeks) demonstrated similar efficacy. Overall, abatacept had a relatively more acceptable safety and tolerability profile, with fewer SAEs, serious infections, acute infusional events and discontinuations due to AEs than the infliximab group. Trial registration number: NCT00095147. Abatacept is a selective T-cell co-stimulation modulator, that modulates the CD80/ CD86:CD28 co-stimulatory signal required for full T-cell activation.1 The mechanism of action of abatacept is fundamentally different to that of other biological disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA). The efficacy of abatacept has previously been demonstrated in patients with RA and an inadequate response to methotrexate (MTX)2 and anti-tumour necrosis factor (TNF) agents,3 respectively. The ATTEST (for ‘‘Abatacept or infliximab vs placebo, a Trial for Tolerability, Efficacy and Safety in Treating rheumatoid arthritis’’) trial was designed to obtain data on the magnitude of the treatment effect in RA of abatacept or infliximab (an established inhibitor of TNF for RA) vs placebo, and to obtain relative efficacy and safety data on these two biological treatments in a single study. The study utilised a double-blind, rando- mised, placebo-controlled design for the first 6 months to validate efficacy responses, and the study duration allowed for the opportunity to directly compare the safety profile of the active biologic treatment groups over 1 year. METHODS Patients Eligible patients met the American College of Rheumatology (ACR) criteria for RA, were at least 18 years of age, had RA for at least 1 year,4 and had an inadequate response to MTX, as demonstrated by ongoing active disease (at randomisation >10 swollen joints, >12 tender joints, and C-reactive protein (CRP) levels >1 mg/dl using a high sensitivity assay (upper limit of the normal range, 0.5)). All patients had received MTX >15 mg/week for >3 months prior to randomisation (stable for at least 28 days) and washed out all DMARDs (>28 days prior) except for MTX. No prior experience of abatacept or anti-TNF therapy was permitted. All patients were screened for tubercu- losis (TB) by purified protein derivative (PPD) testing and chest x ray. The protocol used for TB screening was the same as that employed in the ‘‘Anti-TNF Trial in rheumatoid arthritis with Concomitant Therapy’’ (ATTRACT) trial.5 Ann Rheum Dis 2008;67:1096–1103. doi:10.1136/ard.2007.080002