Inebilizumab for Treatment of IgG4-Related Disease

作者：John H. Stone, Arezou Khosroshahi, Zhang Wen, Emanuel Della‐Torre, Kazuichi Okazaki, Yoshiya Tanaka, Matthias Löhr, N. Schleinitz, Lingli Dong, Hisanori Umehara, Marco Lanzillotta, Zachary S. Wallace, Mikaël Ebbo, George Webster, Francesca Valle, Manu Nayar, Cory A. Perugino, Vinciane Rebours, Xinxin Dong, Yanping Wu, Qing Li, Nishi Rampal, Daniel Cimbora, Emma Culver · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2409712 · 被引用次数：135 · 研究领域：IgG4-Related and Inflammatory Diseases、Neuroendocrine Tumor Research Advances、Sinusitis and nasal conditions

BACKGROUND: IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune-mediated disorder with no approved therapy. Inebilizumab targets and depletes CD19+ B cells and may be effective for treating patients with IgG4-related disease. METHODS: In this phase 3, multicenter, double-blind, randomized, placebo-controlled trial, adults with active IgG4-related disease underwent randomization in a 1:1 ratio to receive inebilizumab (300-mg intravenous infusions on days 1 and 15 and week 26) or placebo for a 52-week treatment period. Participants in both groups received identical glucocorticoid tapers. Glucocorticoids were allowed to treat disease flares, but background immunosuppressants were not permitted. The primary end point was the first treated, adjudicated disease flare during the treatment period, assessed in a time-to-event analysis. Key secondary end points were the annualized flare rate and treatment-free and glucocorticoid-free complete remission. RESULTS: A total of 135 participants with IgG4-related disease underwent randomization: 68 participants were assigned to receive inebilizumab and 67 were assigned to receive placebo. Treatment with inebilizumab reduced flare risk; 7 participants (10%) in the inebilizumab group had at least one flare, as compared with 40 participants (60%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.06 to 0.28; P<0.001). The annualized flare rate was lower with inebilizumab than with placebo (rate rati...