From the Aix Marseille University (M.P., A.M., A.R., C.B., S.D., P.D., J.P., B.A.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie; Aix Marseille University (J.-P.S.), APHM, Hôpital de la Timone, Département de Neuroradiologie; Aix Marseille University (A.M., J.-P.S., A.R., C.B., S.D., P.D., J.P., B.A.), CRMBM UMR 7339, CNRS, Marseille, France.
Neurol Neuroimmunol Neuroinflamm. 2021 Nov 23;9(1). doi: 10.1212/NXI.0000000000001115. Print 2022 Jan.
To determine the frequency of hypogammaglobulinemia and infections in patients with multiple sclerosis (PwMS) receiving rituximab (RTX).
This prospective observational study included all consecutive PwMS receiving RTX at the university hospital of Marseille, France, between 2015 and 2020. Patient visits occurred at least every 6 months.
We included 188 patients (151 with relapsing-remitting MS; the mean age was 43.4 years [SD 12.9], median disease duration 10 years [range 0-36], median Expanded Disability Status Scale 5 [range 0-8], median follow-up 3.5 years [range 1-5.8], and median number of RTX infusions 5 [range 1-9]). Overall, 317 symptomatic infections and 13 severe infections occurred in 133 of 188 (70.7%) and 11 of 188 (5.9%) patients, respectively. After 4 years, 24.4% of patients (95% CI 18.0-33.1) were free of any infection and 92.0% (95% CI 87.1-97.1) had not experienced a severe infection. At RTX onset, the immunoglobulin G (IgG) level was abnormal in 32 of 188 (17%) patients. After RTX, IgG level was <7, <6, <4 and <2 g/L for 83 (44%), 44 (23.4%), 8 (4.2%) and 1 (0.53%) patients, respectively. The risk of infection was associated with reduced IgG levels (multivariate Cox proportional hazards hazard ratio [HR] = 0.86, 95% CI 0.75-0.98, = 0.03). The risk of reduced IgG level <6 g/L increased with age (HR = 1.36, 95% CI 1.05-1.75, = 0.01).
In PwMS receiving RTX, reduced IgG level was frequent and interacted with the risk of infection.
评估接受利妥昔单抗（RTX）治疗的多发性硬化症（MS）患者发生低丙种球蛋白血症和感染的频率。
本前瞻性观察性研究纳入了 2015 年至 2020 年期间在法国马赛大学医院接受 RTX 治疗的所有连续 MS 患者。患者每 6 个月至少就诊一次。
我们纳入了 188 例患者（151 例为复发缓解型 MS；平均年龄 43.4 岁[标准差 12.9]，中位疾病病程 10 年[范围 0-36]，中位扩展残疾状况量表评分为 5 分[范围 0-8]，中位随访时间 3.5 年[范围 1-5.8]，中位 RTX 输注次数为 5 次[范围 1-9]）。188 例患者中有 133 例（70.7%）发生了 317 次有症状感染，11 例（5.9%）发生了 13 次严重感染。4 年后，24.4%（95%置信区间为 18.0-33.1）的患者无任何感染，92.0%（95%置信区间为 87.1-97.1）的患者未发生严重感染。RTX 起始时，188 例患者中有 32 例（17%）免疫球蛋白 G（IgG）水平异常。RTX 后，83 例（44%）、44 例（23.4%）、8 例（4.2%）和 1 例（0.53%）患者的 IgG 水平分别<7、<6、<4 和<2 g/L。感染风险与 IgG 水平降低相关（多变量 Cox 比例风险比例[HR] = 0.86，95%置信区间为 0.75-0.98， = 0.03）。年龄越大，IgG 水平<6 g/L 的风险越高（HR = 1.36，95%置信区间为 1.05-1.75， = 0.01）。
接受 RTX 治疗的 MS 患者中，低 IgG 水平较为常见，与感染风险相关。
