Weinblatt 2006.

Methods	1‐year, multicenter, randomized, double‐blind, placebo‐controlled trial. 2:1 abatacept to placebo ratio of random assignment
Participants	Abatacept N = 959, Placebo N = 482; overall, age: 52.3 +/‐ 11.8 yrs (mean, SD); duration of RA: 9.7 +/‐ 8.9 years (mean, SD) Inclusion: ACR criteria for the diagnosis of RA and functional classes I, II, III, or IV. Patients had to have active disease despite receiving background DMARDs and/or biologic therapy, warranting additional therapy at the discretion of the investigator. Patient’s global assessment of disease activity, VAS >= 20 mm. Had to have been receiving >= 1 biologic and/or non biologic DMARD for at least 3 months, and at a stable dose for at least 28 days prior to day 1 of the trial. Exclusion: unstable or uncontrolled renal, endocrine, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, or neurologic diseases, or any autoimmune disorder other than RA as the main diagnosis. Also, active or chronic recurrent bacterial infections unless treated and resolved, active herpes zoster infection within the previous 2 months, hepatitis B or hepatitis C virus infection, and active or latent TB.
Interventions	Abatacept (10 mg/kg) (N = 959) or placebo (N = 482) by intravenous infusion. Medication (abatacept or placebo) was administered via a 30‐minute intravenous infusion on days 1, 15, and 29, and every 4 weeks thereafter, for a total of 14 doses. All patients were required to continue to receive their background RA therapies (biologic DMARDs, non biologic DMARDs, or a combination of both) at study entry. Stable, low‐dose oral corticosteroids (10 mg/day or less) and/or stable doses of NSAIDs were allowed.
Outcomes	Primary objective: the ASSURE trial was to evaluate the safety of abatacept in patients with active RA, including those with comorbid conditions. Outcomes measured included: occurrence of AEs, SAEs, discontinuations due to AEs, death, clinically significant changes Secondary: Disability Index of the HAQ; patient’s global assessment of disease activity, patient’s global assessment of pain, and physician’s global assessment of disease activity using a 100 mm VAS Results were provided both overall and separately for non‐biologic background and biologic background therapy
Notes	ASSURE ‐ Abatacept Study of Safety in Use with Other RA Therapies Funding: supported by Bristol‐Myers Squibb
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Additional information from author: "'the randomization was done by computer allocation and was maintained by a central independent organization which was not affiliated with the sponsor or the investigators"
Allocation concealment?	Low risk	Additional information from author: "'the randomization was done by computer allocation and was maintained by a central independent organization which was not affiliated with the sponsor or the investigators"
Blinding? Patient assessed	Low risk	"Double"; additional information from author: "the patients, investigators, infusion nurses and pharmacy and study personnel were blinded"
Blinding? Physician assessed	Low risk	"Double"; additional information from author: "the patients, investigators, infusion nurses and pharmacy and study personnel were blinded"
Incomplete outcome data addressed? Efficacy outcomes	High risk	87% of patients in the treatment group and 82% in the placebo group completed 12 months of treatment. 15 people were randomized but not treated with either abatacept or placebo (Figure 1). "Sixteen patients were excluded from the efficacy analysis due to compliance issues at one center." Primary outcome of this study is safety. Judged a high risk of bias due to exclusion of patients from efficacy analysis.
Incomplete outcome data addressed? Safety outcomes	Low risk	87% of patients in the treatment group and 82% in the placebo group completed 12 months of treatment. 15 people were randomized but not treated with either abatacept or placebo (Figure 1). Judged a low risk of bias as safety analysis included all patients treated.
Free of selective reporting?	Low risk	The primary objective of the ASSURE trial was to evaluate the safety of abatacept in patients with active RA..." "All patients who received at least 1 dose of study medication were evaluated for the occurrence of adverse events (AEs), serious adverse events (SAEs), discontinuations due to AEs, death, clinically significant changes in vital signs, physical examination abnormalities, and clinical laboratory test abnormalities."
Free of other bias?	High risk	Funded by drug company. There is evidence that industry‐sponsored trials may overestimate the treatment effect (Bhandari 2004)