NEJM: Obinutuzumab in Active Systemic Lupus Erythematosus Save

A phase 3 trial of obinutuzumab, an anti-CD20 monoclonal antibody, showed potent B-cell depletion and clinical efficacy active systemic lupus erythematosus without evidence of nephritis. 

 

This phase 3, multicenter, double-blind, placebo-controlled trial enrolled adults with active SLE, without proliferative or membranous lupus nephritis, who were on standard therapy. Patients received either intravenous placebo or obinutuzumab (1000 mg) or placebo on day 1 and weeks 2, 24, and 26. The primary end point (week 52) was the SLE Responder Index 4 (SRI-4), defined by a reduction from baseline of at least 4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, no worsening of disease as assessed by the British Isles Lupus Assessment Group (BILAG) 2004 index and Physician’s Global Assessment, and no intercurrent events.

A total of 303 SLE patients were treated; the week 52 SRI-4 responses were: 

Key secondary end points all favored obinutuzumab over placebo (BICLA; sustained reduction in glucocorticoid dose, sustained SRI-4 response, SRI-6 response, and time to first BILAG-defined flare). 

 

Adverse events were equal between treatment groups and serious adverse events in 15.9% and 11.9%, respectively. Deaths were uncommon, with one patient in the obinutuzumab group and 3 in the placebo group.