Table 1

Study design and characteristics

Study	Study design and dosage information	Inclusion criteria	Key exclusion criteria
Baricitinib (RA-BEGIN, NCT01711359)⁹	Patients were randomised 4:3:4 to oral MTX one time per week (N=210), baricitinib 4 mg (monotherapy) one time per day (N=159), or the combination of baricitinib+MTX (N=215)	Patients were ≥18 years Moderately-to-severely active RA Patients had active disease (TJC ≥6 and SJC ≥6) Serum CRP level ≥3.6 mg/L Seropositive for RF or ACPA No prior csDMARD therapy and no prior bDMARD	Recent clinically significant infection and select laboratory abnormalities
Tocilizumab (AMBITION, NCT00109408)¹⁰	Patients were randomised to tocilizumab (TCZ) 8 mg/kg intravenously every 4 weeks (N=286), or to MTX oral capsules, weekly together with folate (>5 mg/week) (N=284)	Patients were ≥18 years ≥3 months of moderately-to-severely active RA SJC of ≥6, TJC ≥8, CRP level ≥1.0 mg/dL or ESR ≥28 mm/h at baseline Oral glucocorticoids and NSAIDs were permitted if stable >6 weeks	Clinically unstable concurrent illnesses Active or untreated latent TB Unsuccessful treatment with TNFi Received MTX within 6 months of randomisation or discontinued MTX previously
Tocilizumab (FUNCTION, NCT01007435)⁸	Patients were randomised to 4 mg/kg TCZ+MTX (N=288), 8 mg/kg TZC+MTX (N=290), 8 mg/kg TCZ+placebo (N=292) or placebo+MTX (N=287); TCZ or placebo were administered intravenously every 4 weeks	Patients were ≥18 years ≤2 years of moderate-to-severe RA SJC of ≥4, TJC of ≥6, CRP level ≥1.0 mg/dL or ESR ≥28 mm/h at baseline Positive RF or ACPA or ≥1 erosion of hands, wrists or feet attributable to RA based on a central radiographic reading	Clinically unstable concurrent illnesses and screened according to local standards Active or untreated latent TB Had been unsuccessfully treated with TNFi Had received MTX 6 months prior to randomisation or had discontinued MTX
Tofacitinib (ORAL-START, NCT01039688)¹¹	Patients were randomised to tofacitinib 5 mg two times per day (BID, N=373) or tofacitinib 10 mg BID (N=397) or MTX (N=186)	Patients were ≥18 years ≥3 months of moderately-to-severely active RA SJC of ≥6, TJC of ≥6, CRP level >7.0 mg/L or ESR >28 mm/h at baseline ≥3 distinct joint erosions on radiographs, positive test for IgM RF or ACPA	Prior treatment with lymphocyte-depleting or alkylating agents Select lab abnormalities History of: another autoimmune rheumatic disease except Sjögren’s syndrome Serious infection Lymphoproliferative disorder Malignancy except adequately treated non-metastatic basal/squamous cell cancer of the skin or cervical carcinoma in situ Evidence of active, latent or inadequately treated Mycobacterium TB infection
Adalimumab PREMIER, NCT00195663)^{6 7}	Patients were randomised to adalimumab 40 mg subcutaneously every other week + weekly oral MTX (N=268); adalimumab 40 mg subcutaneously every other week (adalimumab + placebo; N=274); or weekly oral MTX (N=257)	Patients were ≥18 years <3 years of RA SJC of ≥8, TJC of ≥10, CRP level ≥1.5 mg/dL or ESR ≥28 mm/h at baseline	Patients who had received treatment with MTX, cyclophosphamide, cyclosporine, azathioprine or >2 other DMARDs

ACPA, anti-citrullinated protein antibodies; bDMARD, biologic disease-modifying antirheumatic drugs; CRP, C reactive protein; ESR, erythrocyte sedimentation rate; IgM, immunoglobulin M; MTX, methotrexate; RA, rheumatoid arthritis; RF, rheumatoid factor; SJC, swollen joint count; TB, tuberculosis; TCZ, tocilizumab; TJC, tender joint count; TNFi, tumour necrosis factor inhibitor.