Rituximab in moderate to severe non-renal systemic lupus erythematosus: a reanalysis of the EXPLORER study

Many targeted therapies have been developed for systemic lupus erythematosus (SLE) in recent years and almost all have failed to meet their predesigned endpoints.1 Among these therapies, rituximab (RTX) has reported good results in several open-label studies,2 3 but failed to meet its primary endpoints in two randomised controlled trials (RCTs), EXPLORER and LUNAR.4 5 Among the proposed explanations for these failures, the primary outcome criteria’s lack of sensitivity has been suggested.6 The availability of new SLE response criteria led us to reanalyse the EXPLORER study which assessed RTX efficacy in severe non-renal SLE, using four newly available scores: SLE Response Index-4 (SRI-4), a modified SRI-4 (including reduction of glucocorticoids ≤10 mg/day between days 169 and 365), a modified BILAG-based Clinical Lupus Assessment (mBICLA) and a modified Lupus Low Disease Activity Score (mLLDAS), (online supplementary file 1 for details on criteria).7 8 ### Supplementary data [annrheumdis-2018-214833supp001.docx] The EXPLORER trial was a 52-week, –multicentre, randomised, double-blind placebo-controlled trial of RTX in 257 patients with moderately to severely active non-renal SLE (online supplementary table 1). Patients were randomised at a 2:1 ratio to receive intravenous RTX (1000 mg) or placebo on days 1, …