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 ratio, 0.14; 95% CI, 0.06 to 0.31; P<0.001). More participants in the inebilizumab group than in the placebo group had flare-free, treatment-free complete remission (odds ratio, 4.68; 95% CI, 2.21 to 9.91; P<0.001) and flare-free, glucocorticoid-free complete remission (odds ratio, 4.96; 95% CI, 2.34 to 10.52; P<0.001). Serious adverse events occurred during the treatment period in 12 of the participants (18%) who received inebilizumab and 6 of the participants (9%) who received placebo. CONCLUSIONS Inebilizumab reduced the risk of flares of IgG4-related disease and increased the likelihood of flare-free complete remission at 1 year, confirming the role of CD19-targeted B-cell depletion as a potential treatment for IgG4-related disease. (Funded by Amgen; MITIGATE ClinicalTrials.gov number, NCT04540497.).

中文翻译：

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Inebilizumab 用于治疗 IgG4 相关疾病。


背景 IgG4 相关疾病是一种多器官、复发、纤维炎、免疫介导的疾病，没有批准的治疗方法。Inebilizumab 靶向并耗竭 CD19+ B 细胞，可能对治疗 IgG4 相关疾病患者有效。方法 在这项 3 期、多中心、双盲、随机、安慰剂对照试验中，患有活动性 IgG4 相关疾病的成人以 1：1 的比例接受 inebilizumab（第 1 天和第 15 天以及第 26 周 300 mg 静脉输注）或安慰剂，治疗期为 52 周。两组参与者接受相同的糖皮质激素减量。允许使用糖皮质激素治疗疾病发作，但不允许使用背景免疫抑制剂。主要终点是治疗期间第一次治疗、判定的疾病发作，在事件发生时间分析中进行评估。关键的次要终点是年化耀斑率和无治疗和无糖皮质激素的完全缓解。结果 共有 135 名患有 IgG4 相关疾病的参与者接受了随机分组： 68 名参与者被分配接受 inebilizumab，67 名被分配接受安慰剂。inebilizumab 治疗可降低发作风险;inebilizumab 组有 7 名参与者 （10%） 至少有一次发作，而安慰剂组有 40 名参与者 （60%） （风险比，0.13;95% 置信区间 [CI]，0.06 至 0.28;P<0.001）。inebilizumab 的年化耀斑率低于安慰剂组 （率比，0.14;95% CI，0.06 至 0.31;P<0.001）。与安慰剂组相比，inebilizumab 组的参与者更多，无发作、无治疗的完全缓解（比值比，4.68;95% CI，2.21 至 9.91;P<0.001）和无耀斑、无糖皮质激素的完全缓解（比值比，4.96;95% CI，2.34 到 10.52;P<0.001）。治疗期间，接受 inebilizumab 治疗的 12 名参与者 （18%） 和接受安慰剂的 6 名参与者 （9%） 发生严重不良事件。结论 Inebilizumab 降低了 IgG4 相关疾病发作的风险，并增加了 1 年无耀斑完全缓解的可能性，证实了 CD19 靶向 B 细胞耗竭作为 IgG4 相关疾病的潜在治疗方法的作用。（由 Amgen 资助;MITIGATE ClinicalTrials.gov 号，NCT04540497.）。