Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, United Kingdom.
National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.
Front Immunol. 2022 Jan 12;12:803175. doi: 10.3389/fimmu.2021.803175. eCollection 2021.
Time to relapse after rituximab for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is variable, and optimal retreatment strategy has remained unclear. In AAV following rituximab induction, the study objective was to evaluate clinical and B-cell predictors of relapse in order to develop a retreatment algorithm.
A retrospective observational study was conducted in 70 rituximab-treated ANCA-associated vasculitis patients followed up for over 10 years. Complete response (CR) was defined as Birmingham Vasculitis Activity Score v3.0 = 0. Retreatment was given on clinical relapse, defined as new features or worsening of persistent disease (not by biomarker status). Peripheral B-cell subsets were measured using highly sensitive flow cytometry. Predictors were tested using multivariable Cox regression.
Median time to retreatment for cycles 1-5 were 84, 73, 67, 60, and 73 weeks. Over 467 patient-years follow-up, 158 relapses occurred in 60 patients; 16 (in 15 patients) were major (renal = 7, neurological = 4, ENT = 3, and respiratory = 2). The major-relapse rate was 3.4/100 patient-years. In multivariable analysis, concomitant immunosuppressant [HR, 0.48 (95% CI, 0.24-0.94)], achieving CR [0.24 (0.12-0.50)], and naïve B-cell repopulation at 6 months [0.43 (0.22-0.84)] were associated with longer time to relapse. Personalized retreatment using these three predictors in this cohort would have avoided an unnecessary fixed retreatment in 24% of patients. Area under the receiver operating characteristic for prediction of time to relapse was greater if guided by naïve B-cell repopulation than if previously evaluated ANCA and/or CD19 cells return at 6 months had been used, 0.82 and 0.53, respectively.
Our findings suggest that all patients should be coprescribed oral immunosuppressant. Those with incomplete response or with absent naïve B cells should be retreated at 6 months. Patients with complete response and naïve repopulation should not receive fixed retreatment. This algorithm could reduce unnecessary retreatment and warrant investigation in clinical trials.
利妥昔单抗治疗抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）后的复发时间各不相同，最佳的补救治疗策略仍不清楚。在利妥昔单抗诱导后的 AAV 中，本研究旨在评估临床和 B 细胞预测因子，以制定补救治疗方案。
对 70 例接受利妥昔单抗治疗的 AAV 患者进行回顾性观察研究，随访时间超过 10 年。完全缓解（CR）定义为伯明翰血管炎活动评分 v3.0 = 0。在临床复发时进行补救治疗，定义为新出现的或持续性疾病的加重（不是通过生物标志物状态来定义）。使用高灵敏度流式细胞术测量外周 B 细胞亚群。使用多变量 Cox 回归测试预测因子。
第 1-5 个周期的中位补救治疗时间分别为 84、73、67、60 和 73 周。在超过 467 患者年的随访中，60 名患者中有 158 名发生了复发，其中 16 名（15 名患者）为主要复发（肾脏 = 7、神经 = 4、耳鼻喉 = 3、呼吸 = 2）。主要复发率为 3.4/100 患者年。多变量分析显示，同时使用免疫抑制剂[风险比（HR），0.48（95%置信区间，0.24-0.94）]、达到 CR[0.24（0.12-0.50）]和 6 个月时幼稚 B 细胞再增殖[0.43（0.22-0.84）]与更长的复发时间相关。在该队列中使用这三个预测因子进行个体化补救治疗，可以避免 24%的患者不必要的固定补救治疗。如果以幼稚 B 细胞再增殖为指导，预测复发时间的受试者工作特征曲线下面积大于以前评估的 6 个月时 ANCA 和/或 CD19 细胞恢复，分别为 0.82 和 0.53。
我们的研究结果表明，所有患者都应同时使用口服免疫抑制剂。未达到完全缓解或不存在幼稚 B 细胞的患者应在 6 个月时进行补救治疗。达到完全缓解且幼稚细胞再增殖的患者不应接受固定补救治疗。该方案可以减少不必要的补救治疗，值得在临床试验中进一步研究。
Zotero 插件
