Genovese 2005.

Methods	Multicenter (89 sites). Randomized, double‐blind, phase III trial. 2:1 abatacept to placebo ratio of random assignment. 6‐month study. Stratification by former vs. current users of anti‐TNF therapy.
Participants	Abatacept N = 258, age (mean, SD) 53.4 +/‐ 12.4, % female = 77.1, duration of RA in years (mean, SD) = 12.2 +/‐ 8.5 Placebo N = 133, age (mean, SD) 52.7 +/‐ 11.3, % female = 79.7, duration of RA in years (mean, SD) = 11.4 +/‐ 8.9 Eligibility: ACR criteria for RA, > 18 years old, had RA for at least 1 year and had an inadequate response to anti–TNF therapy with etanercept, infliximab, or both at the approved dose after at least 3 months of treatment. Two groups of patients were enrolled: those receiving anti–TNFtherapy at the time of screening (current users) and those who had previously received such therapy (former users). All users were required to stop taking etanercept or infliximab for at least 28 or 60 days, respectively, before undergoing randomization.
Interventions	Abatacept (10 mg per kg) + DMARD or placebo + DMARD, administered in a 30‐minute intravenous infusion on days 1, 15, and 29 and every 28 days thereafter, up to and including day 141
Outcomes	Two primary: ACR 20 response and the proportion of patients with an improvement of at least 0.3 from baseline in the HAQ (exceeding MCID of 0.22) at 6 months Secondary: ACR 50 and ACR 70 at six months DAS28 Health‐related quality of life (SF‐36) Adverse events
Notes	ATTAIN ‐ Abatacept Trial in Treatment of Anti‐TNF Inadequate Responders Study was also reported in Westhovens 2006 Study supported by Bristol‐Myers Squibb and a grant (5 M01 RR000070) from the National Center for Research Resources, National Institutes of Health
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	"central randomization"
Allocation concealment?	Low risk	"central randomization"
Blinding? Patient assessed	Low risk	"The drug was prepared by pharmacists or other qualified personnel who had no interaction with the patients. Medication was administered intravenously in a blinded fashion by qualified personnel."
Blinding? Physician assessed	Low risk	"All clinical assessments of response were performed in a blinded fashion by the same trained assessors throughout the study."
Incomplete outcome data addressed? Efficacy outcomes	Low risk	86% in treatment group and 74% in placebo group completed 6 months. Used imputation to account for missing data in the analysis. All withdrawals accounted for except that according to the flow diagram, 2 did not meet the eligibility criteria after randomization. "All efficacy analyses included all randomized patients who received at least one dose of study medication". Also, "Two patients in the abatacept group were excluded from the efficacy analysis because of a protocol violation" Judged a low risk of bias given the > 80% completion rate in the treatment group.
Incomplete outcome data addressed? Safety outcomes	Low risk	86% in treatment group and 74% in placebo group completed 6 months. Used imputation to account for missing data in the analysis. All withdrawals accounted for except that according to the flow diagram, 2 did not meet the eligibility criteria after randomization. Judged a low risk of bias given the > 80% completion rate in the treatment group.
Free of selective reporting?	Low risk	"There were two primary end points: the proportion of patients with an ACR 20 response and the proportion of patients with an improvement of at least 0.3 from baseline in the Health Assessment Questionnaire (HAQ) disability index (exceeding the minimal clinically important change of 0.22) at 6 months.
Free of other bias?	High risk	Funded by drug company. There is evidence that industry‐sponsored trials may overestimate the treatment effect (Bhandari 2004)