B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial

作者：Richard Alan Furie, Gustavo Aroca, Matthew D. Cascino, Jay P Garg, Brad H. Rovin, Analía Álvarez, Hilda Esther Fragoso-Loyo, Elizabeth Zuta-Santillan, Thomas Hellmut Schindler, Paul G. Brunetta, Cary M. Looney, Imran Hassan, Ana Malvar · 发表于：Annals of the Rheumatic Diseases · 年份：2022 · DOI：10.1136/annrheumdis-2021-220920 · 被引用次数：459 · 研究领域：Systemic Lupus Erythematosus Research、Renal Transplantation Outcomes and Treatments、Monoclonal and Polyclonal Antibodies Research

OBJECTIVE: Randomised trials of type I anti-CD20 antibodies rituximab and ocrelizumab failed to show benefit in proliferative lupus nephritis (LN). We compared obinutuzumab, a humanised type II anti-CD20 monoclonal antibody that induces potent B-cell depletion, with placebo for the treatment of LN in combination with standard therapies. METHODS: Patients with LN receiving mycophenolate and corticosteroids were randomised to obinutuzumab 1000 mg or placebo on day 1 and weeks 2, 24 and 26, and followed through week 104. The primary endpoint was complete renal response (CRR) at week 52. Exploratory analyses through week 104 were conducted. The prespecified alpha level was 0.2. RESULTS: A total of 125 patients were randomised and received blinded infusions. Achievement of CRR was greater with obinutuzumab at week 52 (primary endpoint, 22 (35%) vs 14 (23%) with placebo; percentage difference, 12% (95% CI -3.4% to 28%), p=0.115) and at week 104 (26 (41%) vs 14 (23%); percentage difference, 19% (95% CI 2.7% to 35%), p=0.026). Improvements in other renal response measures, serologies, estimated glomerular filtration rate and proteinuria were greater with obinutuzumab. Obinutuzumab was not associated with increases in serious adverse events, serious infections or deaths. Non-serious infusion-related reactions occurred more frequently with obinutuzumab. CONCLUSIONS: Improved renal responses through week 104 were observed in patients with LN who received obinutuzumab plus standard thera...