From the Service de Neurologie (A.A., A.M., C.B., S.D., J.P., B.A.), Pôle de Neurosciences Cliniques, and Département de Neuroradiologie (J.-P.S.), Hôpital de la Timone, APHM, Aix Marseille University; and Department of Neurology A (R.M.), Neurologic and Neurosurgical Hospital Pierre Wertheimer, Hospices Civils de Lyon, Bron, France.
Neurol Neuroimmunol Neuroinflamm. 2021 Mar 15;8(3). doi: 10.1212/NXI.0000000000000977. Print 2021 May.
To determine the potential association between infections and rituximab (RTX)-induced hypogammaglobulinemia among patients with CNS inflammatory diseases.
We included in a prospective observational study all consecutive adults with aquaporin 4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG) antibody-positive disorders treated with RTX. Dosing schedule was adapted to memory B-cell measurement.
We included 48 patients (mean age 47 [SD: 14] years; 77% females; 31 AQP4 positive and 17 MOG positive). The median follow-up was 3.6 years (range: 0.9-8.1 years). The median number of RTX infusions was 8 (range: 2-14). The median dosing interval was 6 months (range: 1.7-13.7 months). Sixty-seven symptomatic infections (SIs) were observed in 26 of 48 (54%) patients, including 13 severe infections in 9 (19%). Urinary and lower respiratory tract infections were the most frequent, representing 42% and 21% of SI. At RTX onset, the immunoglobulin G (IgG) level was abnormal in 3 of 48 (6%) patients. After RTX, 15 (31%), 11 (23%), 3 (6%), and 0 of 48 patients showed sustained IgG level <7, <6, <4, and <2 g/L, respectively. On multivariate Cox proportional hazards analysis, the main variables explaining the risk of SI were the presence of urinary tract dysfunction (hazard ratio [HR] = 34, 95% CI 4-262, < 0.001), the dosing intervals (HR = 0.98, 95% CI 0.97-0.99, < 0.001), and the interaction between IgG level and urinary tract dysfunction (HR = 0.67, 95% CI 0.53-0.85, < 0.005). IgG level <6 g/L during RTX was associated with male sex (HR = 4, 95% CI 1.4-11.4, < 0.01) and previous immunosuppression (HR = 3.4, 95% CI 1.2-10, < 0.05).
RTX used as maintenance therapy in CNS inflammatory diseases is frequently associated with reduced IgG level and increases the infection risk of the most vulnerable patients.
确定中枢神经系统炎症性疾病患者的感染与利妥昔单抗（RTX）诱导的低丙种球蛋白血症之间的潜在关联。
我们纳入了一项前瞻性观察性研究中的所有连续接受水通道蛋白 4（AQP4）或髓鞘少突胶质细胞糖蛋白（MOG）抗体阳性障碍治疗的成人患者，并接受 RTX 治疗。剂量方案根据记忆 B 细胞的测量进行调整。
我们纳入了 48 名患者（平均年龄 47 [SD：14] 岁；77%为女性；31 名 AQP4 阳性，17 名 MOG 阳性）。中位随访时间为 3.6 年（范围：0.9-8.1 年）。中位数 RTX 输注次数为 8 次（范围：2-14 次）。中位数给药间隔为 6 个月（范围：1.7-13.7 个月）。在 48 名患者中的 26 名（54%）患者中观察到 67 次有症状感染（SI），包括 9 名（19%）患者的 13 次严重感染。尿和下呼吸道感染最常见，分别占 SI 的 42%和 21%。在 RTX 开始时，48 名患者中有 3 名（6%）患者的免疫球蛋白 G（IgG）水平异常。在 RTX 后，分别有 15 名（31%）、11 名（23%）、3 名（6%）和 0 名患者的 IgG 水平持续低于 7、6、4 和 2 g/L。在多变量 Cox 比例风险分析中，解释 SI 风险的主要变量是尿路功能障碍的存在（风险比 [HR] = 34，95%CI 4-262，<0.001）、给药间隔（HR = 0.98，95%CI 0.97-0.99，<0.001）和 IgG 水平与尿路功能障碍之间的相互作用（HR = 0.67，95%CI 0.53-0.85，<0.005）。RTX 期间 IgG 水平<6 g/L 与男性（HR = 4，95%CI 1.4-11.4，<0.01）和先前的免疫抑制（HR = 3.4，95%CI 1.2-10，<0.05）有关。
RTX 作为中枢神经系统炎症性疾病的维持治疗，常与 IgG 水平降低有关，并增加了最脆弱患者的感染风险。
