Efficacy and Safety of Obinutuzumab in Active Systemic Lupus Erythematosus

Obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody, induces potent B-cell depletion and is approved for the treatment of active lupus nephritis. Its efficacy and safety in patients with active systemic lupus erythematosus (SLE) are yet to be determined.

We conducted a phase 3, multicenter, double-blind, placebo-controlled trial involving adults with active SLE but without proliferative or membranous lupus nephritis who were receiving standard therapy. Patients were randomly assigned in a 1:1 ratio to receive obinutuzumab (1000 mg) or placebo on day 1 and weeks 2, 24, and 26. In the prespecified analysis, the primary end point at week 52 was a response on 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 (i.e., major concomitant-therapy violation, receipt of rescue medication, or early discontinuation of trial participation due to death, lack of efficacy, or adverse events).