Obinutuzumab plus standard therapy is efficacious in managing active lupus nephritis

1. In this randomized trial, obinutuzumab plus standard therapy was more efficacious than standard therapy alone in providing a complete renal response in adults with active lupus nephritis.

2. There were no unexpected safety signals identified for obinutuzumab.

Evidence Rating Level: 1 (Excellent)

Study Rundown: There have been many advancements in the management of lupus nephritis, however, the goal to sufficiently improve short- and long-term outcomes has yet to be met. Obinutuzumab is a humanized glycoengineered type II anti-CD20 monoclonal antibody that has been approved for the treatment of chronic lymphocytic leukemia and follicular lymphoma. Previous trials have compared obinutuzumab plus standard therapy to standard therapy alone in patients with active lupus nephritis and found a clinically meaningful renal response. This phase three, randomized controlled trial aimed to evaluate the efficacy and safety of obinutuzumab as compared to placebo when added to standard therapy of mycophenolate mofetil and glucocorticoids in patients with active proliferative lupus nephritis. Patients who met the inclusion criteria were randomly assigned in a 1:1 ratio to receive either obinutuzumab in one of two dose schedules or a placebo. All patients received standard therapy with mycophenolate mofetil and oral prednisone. The primary end point was a complete renal response at week 76. Results from this study found that among adults with active lupus nephritis, obinutuzumab plus standard therapy was more efficacious than standard therapy alone in providing a complete renal response.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: This randomized, placebo-controlled trial evaluated the efficacy and safety of obinutuzumab plus standard therapy, as compared to placebo, in patients with active proliferative lupus nephritis. Adult patients who met criteria for systemic lupus erythematosus and had active class III or IV lupus nephritis were eligible for this study. Exclusion criteria included eGFR lower <30 ml/min/1.73m² or end-stage kidney disease requiring dialysis or transplant. A total of 271 patients were randomly assigned in a 1:1 ratio to receive either 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; n=135, combined) or placebo (n=136). The primary end point of the study was complete renal response at week 76, as defined by urinary protein-to-creatinine ratio of less than 0.5, an eGFR of at least 85% of the baseline value, and no intercurrent events. A complete renal response at week 76 was observed in 46.4% of patients in the obinutuzumab group and 33.1% of patients in the placebo group (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 2.0 to 24.8; p=0.02). A complete renal response at week 76 with a prednisone dose of 7.5 or lower between weeks 64 and 76 was observed more in the obinutuzumab group than placebo (42.7% vs. 30.9%; adjusted difference, 11.9 percentage points; 95% CI, 0.6 to 23.2; p=0.04), and a urinary protein-to-creatinine ratio lower than 0.8 without an intercurrent event was more common with obinutuzumab than with placebo (55.5% vs. 41.9%; adjusted difference, 13.7 percentage points; 95% CI, 2.0 to 25.4; P=0.02). There were no unexpected safety signals identified. Overall, results from this study found that obinutuzumab plus standard therapy was more efficacious than standard therapy alone in achieving complete renal response in patients with active lupus nephritis.

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