Klareskog 2004 (TEMPO).

Methods	Randomisation method not described Allocation concealment Triple blinding Multicentre (N = 19), parallel group study Power calculation for sample size No of participants randomised = 686 No of participants analysed = 682 (4 did not receive treatment) Modified intention‐to‐treat analysis (those who received the study drug). Other missing data estimated by LOCF or linear extrapolation Source of funding: Wyeth Research (pharmaceutical company)
Participants	Inclusion: ≥ 18 years of age; disease duration 6 months to 20 years; active RA; less than satisfactory response to at least 1 DMARD (except MTX); treatment with MTX in last 6 months; toxic effects from previous MTX treatment Exclusion: Previous treatment with etanercept or other TNF antagonist; previous treatment with immunosuppressive drugs in past 6 months; use or any investigative drug or biological agent in past 3 months; use of any other DMARD or steroid injection in past 4 weeks; presence of co‐morbidity Location: 17 centres in Europe, Australia and Israel
Interventions	Etanercept 25 mg SC twice weekly + MTX Etanercept 25 mg SC twice weekly MTX (7.5 mg escalating to 20 mg) oral/week PBO controlled Duration: 3 years
Outcomes	ACR20, ACR50, ACR70 Radiographic: TSS; Erosion Score; Joint Space Narrowing Score HAQ; DAS Satisfaction Adverse events Withdrawals
Notes	Trial has continued open label
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method not described
Allocation concealment (selection bias)	Low risk	Centralised telephone randomisation
Blinding (performance bias and detection bias) Clinical outcomes	Low risk	Triple blinding (participants, investigators and assessors)
Incomplete outcome data (attrition bias) Clinical outcomes	Low risk	Clear descriptions of methods for dealing with missing data (LOCF, linear extrapolation and assumption that participants withdrawing from the study had no response to treatment)
Selective reporting (reporting bias)	Low risk	No access to prior protocol to check for selective reporting but wide range of outcomes measured
Other bias	Unclear risk	Drug company funding with no guarantees described to prevent influence on results