Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis
In the phase 3 REGENCY trial, adding obinutuzumab to standard therapy produced significantly more complete renal responses than standard therapy alone in patients with active lupus nephritis.
Background
Lupus nephritis is a serious manifestation of systemic lupus erythematosus in which complete renal remission remains difficult to achieve with standard immunosuppression. Obinutuzumab is a humanized type II anti-CD20 monoclonal antibody that produces potent B-cell depletion. An earlier phase 2 trial had suggested better renal responses with obinutuzumab added to standard therapy.
Study design
REGENCY was a phase 3, randomized, double-blind, placebo-controlled trial that randomized 271 adults with biopsy-proven active lupus nephritis 1:1 to obinutuzumab or placebo, both added to standard therapy with mycophenolate mofetil and oral prednisone. The primary endpoint was complete renal response at week 76, defined by a urinary protein-to-creatinine ratio below 0.5, an estimated glomerular filtration rate of at least 85% of baseline, and no intercurrent event.
Key findings
A complete renal response at week 76 occurred in 46.4% of the obinutuzumab group versus 33.1% of the placebo group (adjusted difference 13.4 percentage points; 95% CI 2.0 to 24.8; P=0.02). Secondary endpoints, including complete renal response with a prednisone dose of 7.5 mg per day or lower and a urinary protein-to-creatinine ratio below 0.8 without an intercurrent event, also favored obinutuzumab. More serious adverse events, mainly infections and COVID-19-related events, occurred with obinutuzumab, but no unexpected safety signals were identified.
Clinical implications
These results support obinutuzumab plus standard therapy as a more effective option than standard therapy alone for achieving complete renal response in active lupus nephritis. The added benefit must be weighed against a higher rate of serious infections, warranting attention to infection monitoring and prophylaxis.
Category
Research
Source
New England Journal of Medicine
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