Concomitant medications were permitted between days 1– 197: oral corticosteroids ((10 mg of prednisone or equivalent daily (stable for >25 out of 28 days prior to randomisation)), and/or stable non-steroidal anti-inflammatory drugs (NSAIDs) including acetyl salicylic acid, and analgesics not containing aspirin or NSAIDs. No MTX dose adjustments were permitted except in the occurrence of adverse events (AEs). Between days 198–365, dose modification was permitted for MTX ((25 mg weekly) and oral corticosteroids ((10 mg prednisone or equivalent daily); hydroxychloroquine, sulfasalazine, gold, or azathioprine were also permitted. Premedication prior to infusions of study drug was left at the discretion of the investigator (not required by protocol). Study design ATTEST was a randomised, double-blind, double-dummy, placebo- and active (infliximab)-controlled, 12-month global trial. Adult patients with active RA and an inadequate response to MTX were randomised by centre in a 3:3:2 ratio to 6 months of abatacept (approximating 10 mg/kg), infliximab (3 mg/kg), or placebo treatment by intravenous (IV) infusion, on a background of MTX. Assessors, physicians and patients were blinded to the treatment group assignment for 1 year. The study was approved by the institutional review boards and independent ethics committees at participating sites, and was carried out in accordance with the ethical principles of the Declaration of Helsinki. All patients provided written informed consent before randomisation. Treatment with placebo was limited to days 1–197 to provide internal validity to the trial design and the clinical response rates of the two active treatment groups. On day 198, placebo- treated patients were reallocated to abatacept (with blinding maintained). Patients initially randomised to abatacept or infliximab continued their treatment. Clinical efficacy and safety assessments are presented for the abatacept, placebo and infliximab groups up to day 197, and for the abatacept and infliximab groups up to day 365 (excluding patients in the placebo group who were reallocated to abatacept at day 198). Study drugs Abatacept was dosed according to weight: patients weighing less than 60 kg, 60–100 kg, or more than 100 kg received 500 mg, 750 mg, or 1000 mg of abatacept, respectively. Infliximab was dosed at 3 mg/kg for all patients. Abatacept was administered by IV infusion on days 1, 15 and 29, and every 28 days thereafter, up to and including day 337 (with normal saline received on day 43). Infliximab was administered on days 1, 15, 43 and 85, and every 56 days thereafter (normal saline was received at the remaining visit days). Two IV bags were infused simultaneously to ensure blinding to treatment group assign- ment, one over 30 min (abatacept or placebo) and one over 2 h (infliximab or placebo). Objectives The primary endpoint was to evaluate a reduction in disease activity, measured by Disease Activity Score 28 (based on erythrocyte sedimentation rate levels; DAS28 (ESR)) with abatacept vs placebo at 6 months. Secondary endpoints included mean reduction in DAS28 (ESR) with infliximab vs placebo at 6 months. Additional secondary endpoints at 6 months and 1 year included: mean reduction in DAS28 (ESR) with abatacept vs infliximab; DAS28 (ESR) European Ann Rheum Dis 2008;67:1096–1103. doi:10.1136/ard.2007.080002 Extended report League Against Rheumatism (EULAR) responses;6 low disease activity score (LDAS; DAS28 (ESR) (3.2); DAS28 (ESR)-defined remission (DAS28 (ESR) ,2.6); ACR 20, 50 and 70 responses;7 Health Assessment Questionnaire Disability Index (HAQ-DI) response rates (>0.3 improvement from baseline); and mean changes in the physical and mental component summary (PCS and MCS, respectively) scores, and eight subscales of the Short Form-36 (SF-36). Tertiary endpoints included comparative safety at 1 year between the abatacept and infliximab groups. Clinical assessments Disease activity was assessed using the validated DAS28 (ESR).8 The EULAR criteria were used to assess good responses (endpoint DAS28 (ESR) of (3.2 and an improvement from baseline of >1.2).6 Signs and symptoms of RA were evaluated using ACR 20, 50 and 70 response rates based on the ACR criteria.7 Physical function was assessed using the HAQ-DI.9 Health- related quality of life (HRQoL) was assessed using the SF-36.10 Safety All patients who received at least one dose of study drug were evaluated for safety, including all reported AEs, serious AEs (SAEs), and clinically significant changes in vital signs, physical exams, and clinical laboratory test abnormalities. Sample size calculation The sample size and power were calculated to detect a treatment difference in the primary analysis of a mean change from baseline in DAS28 (ESR) for the abatacept vs placebo groups at day 197. Prospectively, this study was not powered with a superiority or non-inferiority design to compare the two active arms. Statistical analyses All patients who received at least one dose of study medication were assessed for efficacy and safety (intent-to-treat popula- tion). At day 197, the abatacept or infliximab groups were compared with the placebo group by analyses of covariance (ANCOVA) for mean changes from baseline in DAS28 (ESR) and in the SF-36 (PCS and MCS). The model included the change as the dependent variable, with treatment group as a main effect and the baseline score as an additional covariate. The proportion of patients with ACR 20, 50 and 70 responses, LDAS, DAS28-defined remission, a good EULAR response and a clinical meaningful HAQ-DI response was calculated. The x2 test was performed to evaluate the differences (and 95% CIs) between the abatacept or infliximab groups and placebo. At day 365, the reference group was changed to infliximab. Patients who discontinued the study prematurely were considered as non-responders subsequent to the time of discontinuation for ACR 20, 50 and 70 responses, good EULAR responses and clinically meaningful HAQ-DI responses. For all continuous measurements (mean changes in DAS28, SF- 36 and the HAQ-DI score), LDAS and DAS28-defined remission the last observations prior to the discontinuation were carried forward (LOCF). To access the effect of antirheumatic medica- tions on the abatacept and infliximab treatment groups, a predefined sensitivity analysis was conducted on the data with the last DAS28 (ESR) score just prior to the initiation of the additional DMARD, or any increase in MTX or corticosteroid use during treatment days 198–365 carried forward. 1097