Moreland 2002.

Methods	Multicenter, multi‐national, randomized, double‐blind, placebo‐controlled trial. Phase II. Trial duration = 85 days.
Participants	Abatacept N = 214, age (mean, SD) 51.5 +/‐ 11.5, % female = 69, duration of RA in years (mean, SD) = 3.4+/‐2.1, 94% white, 3% black Placebo N = 32, age (mean, SD) 48.3 +/‐ 11.7, % female = 81, duration of RA in years (mean, SD) = 3.2 +/‐ 2.0, 94% white, 4% black Mean duration of RA: 3.4 yrs +/‐ 2 yrs (SD) Inclusion criteria: ACR criteria for RA and functional class I, II, or III. Age 18 to 65 years with a disease duration < 7 years. Treated unsuccessfully with at least 1 DMARD or etanercept. Patients had to agree to discontinue any DMARD or etanercept treatment from 28 days prior to the day 1 dose of the study medication through study day 85. Treatment with low‐dose corticosteroids or NSAIDs could be continued provided the prescribed dosage remained stable. Negative tuberculin skin test within the last 6 months or documentation of course of adequate chemoprophylaxis of tuberculosis. Exclusion: pregnancy, nursing
Interventions	Patients were randomized to 1 of 7 treatment groups: abatacept at 0.5 mg/kg, 2 mg/kg, or 10 mg/kg; LEA29Y at 0.5 mg/kg, 2 mg/kg, or 10 mg/kg; or placebo. Study medication was administered on days 1, 15, 29, and 57. No concurrent DMARDs were allowed. Days 1 to 85 were considered to be the treatment period; follow up continued through day 169 For this review, abatacept 10 mg/kg (N = 32) and placebo (N = 32) were considered
Outcomes	Primary: ACR 20% on day 85 Secondary: ACR 50, ACR 70, core set measures Adverse events.
Notes	Funding source not clearly stated. Employees of Bristol Myers Squibb are listed as co‐authors.
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	"Each subject was assigned a unique, sequential subject number beginning with 001, 002, 003, etc., for identification throughout the study. The subject number was not to be used for any other participant at the site. Treated subjects who did not complete the study were not replaced. Randomization schedules were generated and kept by the Biostatistics and Data Management Department of BMS." (Additional info obtained from BMS)
Allocation concealment?	Low risk	"The Centralized Randomization Center (CRC) assigned each subject a unique, non‐sequential, randomization number corresponding with the treatment kit number. The Investigator Project Notebook contained instructions on the Centralized Enrolment and Randomization System. Randomization schedules were generated and kept by the Biostatistics and Data Management Department of BMS." (Additional info obtained from BMS).
Blinding? Patient assessed	Low risk	"Subjects and clinical assessor(s) were not aware of the treatment being administered. Study drug was required to be supplied to study personnel in a manner such that neither study personnel nor subjects were aware of whether they were receiving active drug or placebo." (Additional information provided by BMS).
Blinding? Physician assessed	Low risk	"Subjects and clinical assessor(s) were not aware of the treatment being administered. Study drug was required to be supplied to study personnel in a manner such that neither study personnel nor subjects were aware of whether they were receiving active drug or placebo." (Additional information provided by BMS).
Incomplete outcome data addressed? Efficacy outcomes	Low risk	81% of total study participants completed the 85 days of the study. 22% of abatacept group (all doses) discontinued. Missing data were imputed using LOCF or non‐responders for ACR response. All withdrawals accounted for. "All efficacy analyses were carried out on the intent‐to‐treat population, defined as all randomized subjects who received at least 1 infusion of study medication." (2 people were dropped from the study after randomization). Judged a low risk of bias because the overall trial completion rate was > 80%.
Incomplete outcome data addressed? Safety outcomes	Low risk	81% of total study participants completed the 85 days of the study. 22% of abatacept group (all doses) discontinued. All withdrawals accounted for. Adverse events described for the population of randomized subjects who received at least 1 infusion of study medication (2 people were dropped from the study after randomization). Judged a low risk of bias because the overall trial completion rate was > 80%.
Free of selective reporting?	Low risk	ACR 20 specified as primary outcome and is appropriate
Free of other bias?	High risk	Funded by drug company. There is evidence that industry‐sponsored trials may overestimate the treatment effect (Bhandari 2004)