Navarra 2011.

Study characteristics
Methods	Country: international Setting: multicenter Study design: RCT
Participants	867/865 randomized/analyzed (2 withdrawn before 1st dose); all ≥ 18 years belimumab (1 mg/kg): analyzed (n = 288); age (35.0 ± 10.6 years); M/F (17/271) belimumab (10 mg/kg): analyzed (n = 290); age (35.4 ± 10.8 years); M/F (10/280) placebo: analyzed (n = 287); age (36.2 ± 11.8 years); M/F (17/270) Inclusion criteria Diagnosis of SLE according to ACR revised criteria, active disease (SELENA–SLEDAI score ≥ 6), seropositivity as defined by positive ANA (titre ≥1:80) or anti‐dsDNA (≥30 IU/mL) test results, stable treatment regimen ≥ 30 days before the first study dose Exclusion criteria Severe active lupus nephritis or CNS lupus; pregnancy; previous treatment with any B‐lymphocyte‐targeted drug (including rituximab),intravenous cyclophosphamide within 6 months of enrolment, and intravenous Ig or prednisone (> 100 mg/day) within 3 months
Interventions	1 mg/kg belimumab, 10 mg/kg belimumab, or placebo by intravenous (IV) infusion over 1 hour on days 0, 14, and 28 and every 28 days through week 48
Outcomes	Efficacy measures 1. SLE responder index (SRI) response rate 2. British Isles Lupus Assessment Group (BILAG) A organ domain score 3. Physician’s global assessment score 4. Physical component summary (PCS) score 5. Decrease in mean prednisone dose ≥ 25% from baseline 6. SLE flare index Biologic markers 1. Serum Ig, complement (C3 and C4), autoantibodies Safety measures: 1. Adverse events (AEs) 2. Serious Adverse Events 3. Discontinuations due to AEs 4. Deaths 5. Malignant neoplasms 6. Infections 7. Infusion reactions 8. Laboratory abnormalities
Notes	Number of withdrawals: placebo (n = 61), belimumab 1mg/kg (n = 48), and belimumab 10mg/kg (n = 49) Follow‐up time: 52 weeks Study funded by Human Genome Sciences and GlaxoSmithKline
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomized in a 1:1:1 ratio to placebo, or belimumab 1 mg/kg or 10 mg/kg and assigned to treatment by use of a central interactive voice response system.
Allocation concealment (selection bias)	Low risk	Participants who underwent all screening procedures and met the entry criteria were enrolled in the study and assigned to treatment by use of a central interactive voice response system, with the central randomization list provided by Human Genome Sciences.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants, investigators, study co‐ordinators, and sponsors were masked to treatment assignment during intravenous administration of the drug.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Participants, investigators, study co‐ordinators, and sponsors were masked to treatment assignment during assessment of the participants every 4 weeks during the 52‐week trial until the database was locked.
Incomplete outcome data (attrition bias) All outcomes	High risk	Proportion of missing outcomes high in both arms (17% in belimumab arm; 21% in placebo arm).
Selective reporting (reporting bias)	Low risk	Includes all expected outcomes, including those that were prespecified
Other bias	Low risk	The study appears to be free of other sources of bias