Kremer 2003.

Methods	Six‐month, double‐blind, randomized, placebo‐controlled trial. Phase II. Multicenter, multinational. 2:1 abatacept to placebo ratio of random assignment.
Participants	Abatacept N = 220, age (mean, SD) 54.7 range 23 to 80 years, % female = 66, duration of RA in years (mean, SD) = 8.9 +/‐ 8.3 Placebo N = 119, age (mean, SD) 55.8 range 17 to 83 years, % female = 75.0, duration of RA in years (mean, SD) = 9.7 +/‐ 9.8 Patients with rheumatoid arthritis who had an inadequate response to methotrexate Inclusion criteria: ACR criteria for RA & functional class I, II, or III with active disease. Treated with MTX (10 to 30 mg weekly) for at least 6 months and to have received a stable dose for 28 days before enrolment. Concomitant medications: All patients continued to receive methotrexate. All other DMARDs were discontinued. Stable low‐dose corticosteroids and NSAIDs were permitted. Exclusion: nursing or pregnant
Interventions	Abatacept 2 mg/kg + MTX (N = 105); Abatacept 10 mg/kg + MTX (N = 115); Placebo + MTX (N = 119) Abatacept or placebo was infused intravenously over a 30‐minute period on days 1, 15, and 30 and monthly thereafter for a total of 6 months. Only 10 mg/kg arm reported for this review.
Outcomes	Primary: ACR 20 response at 6months Secondary outcomes: ACR 50 & 70 Health‐related quality of life (SF‐36) Adverse events
Notes	Study was also reported in Kremer 2003 and Emery 2006. The study sponsor (Bristol Myers Squibb) was involved in the design of the study, collection of the data, and analysis of the data. The academic investigators had access to the data and were responsible for interpreting the data.
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	"Double blind". Additional info provided by BMS: subjects and clinical assessor(s) were blinded to treatment assignment
Blinding? Physician assessed	Low risk	"Double blind". "Assessments were performed by rheumatologists or trained professional staff members who were unaware of patients’ treatment assignments and were not involved in the infusion of CTLA4Ig or placebo."
Incomplete outcome data addressed? Efficacy outcomes	High risk	86% of abatacept group and 66% of placebo completed 6 months of treatment. At 12 months (results reported in Kremer 2005), 78% of abatacept group and 60% of placebo completed the study. Missing data were imputed for analysis. "Patients who discontinued the study because of worsening disease were considered to have had no response; for those who discontinued the study for other reasons the values for the last efficacy observation were carried forward." All withdrawals accounted for. Efficacy outcomes reported for total number of randomized patients. Judged a high risk of bias due to > 20% drop‐out rate at 12 months in the treatment group.
Incomplete outcome data addressed? Safety outcomes	High risk	86% of abatacept group and 66% of placebo completed 6 months of treatment. At 12 months (results reported in Kremer 2005), 78% of abatacept group and 60% of placebo completed the study. Missing data were imputed for analysis. "Patients who discontinued the study because of worsening disease were considered to have had no response; for those who discontinued the study for other reasons the values for the last efficacy observation were carried forward." All withdrawals accounted for. Safety outcomes reported for total number of randomized patients. Judged a high risk of bias due to > 20% drop‐out rate at 12 months in the treatment group.
Free of selective reporting?	Low risk	"The primary efficacy variable was the percentage of patients who had a 20 percent improvement according to ACR criteria (an ACR 20 response) at six 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)