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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
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, …
MS, CC, EL and CR contributed equally.
Handling editor Josef S Smolen
Contributors MS, CC and M-ET did the figures. MS, EL and CR wrote the manuscript. MS and TB conducted the data analysis (statistics). PD, LC, JS, PB, EL and CR took part in the design of the study and of the reanalysis. All authors approved the last version of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests MS, TB, PD, LC, JS, PB and CC declare no conflict of interest. CR has received consultancy and speaking fees from AstraZeneca, Roche, Glenmark, BMS, Lilly, UCB and Janssen. EL has received consultancy and speaking fees from GSK and UCB. M-ET has received consultancy fees and/or research funding from BMS, Roche, Lilly and UCB. Roche Pharmaceuticals provided freely EXPLORER raw data but did not take part in neither the analysis nor the writing of the manuscript.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.