Safety and efficacy of belimumab after B cell depletion therapy in systemic LUPUS erythematosus (BEAT-LUPUS) trial: statistical analysis plan

BackgroundThere is limited evidence that rituximab, a B cell depletion therapy, is an effective treatment for systemic lupus erythematosus (SLE). Data on the mechanisms of B cell depletion in SLE indicate that the combination of rituximab and belimumab may be more effective than rituximab alone. The safety and efficacy of belimumab after B cell depletion therapy in systemic LUPUS erythematosus (BEAT-LUPUS) trial aims to determine whether belimumab is superior to placebo, when given 4-8weeks after treatment with rituximab. This article describes the statistical analysis plan for this trial as an update to the published protocol. It is written prior to the end of patient follow-up, while the outcome of the trial is still unknown.Design and methodsBEAT-LUPUS is a randomised, double-blind, phase II trial of 52weeks of belimumab versus placebo, initiated 4-8weeks after rituximab treatment. The primary outcome is anti-dsDNA antibodies at 52weeks post randomisation. Secondary outcomes include lupus flares and damage, adverse events, doses of concomitant medications, quality of life, and clinical biomarkers. We describe the trial's clinical context, outcome measures, sample size calculation, and statistical modelling strategy, and the supportive analyses planned to evaluate for mediation of the treatment effect through changes in concomitant medication doses and bias from missing data.DiscussionThe analysis will provide detailed information on the safety and effectiveness of belimumab. It will be implemented from July 2020 when patient follow-up and data collection is complete.Trial registrationISRCTN: 47873003. Registered on 28 November 2016.EudracT: 2015-005543-14. Registered on 19 November 2018.