Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis

Obinutuzumab, a humanized type II anti-CD20 monoclonal antibody, provided significantly better renal responses than placebo in a phase 2 trial involving patients with lupus nephritis receiving standard therapy.

In a phase 3, randomized, controlled trial, we assigned adults with biopsy-proven active lupus nephritis in a 1:1 ratio to receive obinutuzumab in one of two dose schedules (1000 mg on day 1 and at weeks 2, 24, 26, and 52, with or without a dose at week 50) or placebo. All patients received standard therapy with mycophenolate mofetil, along with oral prednisone at a target dose of 7.5 mg per day by week 12 and 5 mg per day by week 24. The primary end point was a complete renal response at week 76, defined by a urinary protein-to-creatinine ratio of less than 0.5 (with protein and creatinine both measured in milligrams), an estimated glomerular filtration rate of at least 85% of the baseline value, and no intercurrent event (i.e., rescue therapy, treatment failure, death, or early trial withdrawal). Key secondary end points at week 76 included a complete renal response with a prednisone dose of 7.5 mg per day or lower between weeks 64 and 76 and a urinary protein-to-creatinine ratio lower than 0.8 without an intercurrent event.