From the Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
Neurol Neuroimmunol Neuroinflamm. 2022 Jul 19;9(5). doi: 10.1212/NXI.0000000000001179. Print 2022 Sep.
To investigate the frequency and predictors of hypogammaglobulinemia during long-term rituximab (RTX) treatment in patients with neuromyelitis optica spectrum disorder (NMOSD) and its association with infections.
We retrospectively reviewed the data of patients with NMOSD who received RTX through the maintenance regimen based on memory B-cell detection for at least 1 year from 2006 to 2021 at an institutional referral center for NMOSD.
A total of 169 patients received a median of 10 courses (range 1-27) of RTX reinfusion after induction over a median of 8 (range, 1-15) years. Their mean serum immunoglobulin (Ig)G level began to decline significantly after 2 years of treatment, steadily declined at a rate of 2%-8% per year for the following 8 years, and then plateaued after 10 years. The proportion of patients with hypo-IgG (<6 g/L) increased from 1.2% after 1 year of treatment to 41% after 14 years of treatment. While being treated with RTX, 58 (34%) patients had 114 infections, of whom 14 (8%) patients had 15 severe infections. Multivariable logistic regression analyses identified duration of RTX treatment in years (odds ratio [OR] 1.234, 95% confidence interval [CI] 1.015-1.502), mean annual RTX dose (OR 0.063, 95% CI 0.009-0.434), history of mitoxantrone (OR 3.318, 95% CI 1.109-9.93), hypo-IgG at baseline (OR 40.552, 95% CI 3.024-543.786), and body mass index >25 kg/m (OR 4.798, 95% CI 1.468-15.678) as independent predictors of hypo-IgG. The risk of infection during RTX treatment was independently associated with high Expanded Disability Status Scale scores (OR 1.427, 95% CI 1.2-1.697) and relapses during RTX treatment (OR 1.665, 95% CI 1.112-2.492), but not with hypogammaglobulinemia.
Over 14 years of long-term RTX treatment, IgG levels gradually decreased, and the frequency of hypo-IgG increased to 41% of the patients. Patients with prolonged memory B-cell depletion after RTX, previous mitoxantrone history, hypo-IgG at baseline, or obesity were at risk of developing RTX-induced hypogammaglobulinemia. Nevertheless, infection rates remained low during treatment, and reduced immunoglobulin levels were not associated with an increased incidence of infections.
研究长期接受利妥昔单抗（RTX）治疗的视神经脊髓炎谱系疾病（NMOSD）患者发生低丙种球蛋白血症的频率和预测因素，及其与感染的关系。
我们回顾性分析了 2006 年至 2021 年在一家 NMOSD 机构转诊中心，根据记忆 B 细胞检测结果接受至少 1 年 RTX 维持治疗的 NMOSD 患者的数据。
共有 169 例患者在中位 8 年（范围 1-15 年）期间接受了中位数为 10 个疗程（范围 1-27 个）的诱导后 RTX 再输注。他们的平均血清免疫球蛋白（Ig）G 水平在治疗 2 年后开始显著下降，在随后的 8 年内以每年 2%-8%的速度稳定下降，然后在 10 年后趋于稳定。低 IgG（<6 g/L）患者的比例从治疗 1 年后的 1.2%增加到 14 年后的 41%。在接受 RTX 治疗期间，58 例（34%）患者发生了 114 次感染，其中 14 例（8%）患者发生了 15 次严重感染。多变量逻辑回归分析确定了 RTX 治疗持续时间（年）（比值比[OR] 1.234，95%置信区间[CI] 1.015-1.502）、平均每年 RTX 剂量（OR 0.063，95%CI 0.009-0.434）、米托蒽醌史（OR 3.318，95%CI 1.109-9.93）、基线时低 IgG（OR 40.552，95%CI 3.024-543.786）和体重指数（BMI）>25 kg/m（OR 4.798，95%CI 1.468-15.678）是低 IgG 的独立预测因子。RTX 治疗期间感染的风险与高扩展残疾状况量表评分（OR 1.427，95%CI 1.2-1.697）和 RTX 治疗期间复发（OR 1.665，95%CI 1.112-2.492）独立相关，但与低丙种球蛋白血症无关。
在长达 14 年的长期 RTX 治疗中，IgG 水平逐渐下降，低 IgG 血症的发生率增加到 41%。RTX 后记忆 B 细胞耗竭时间延长、既往米托蒽醌史、基线时低 IgG 或肥胖的患者存在发生 RTX 诱导性低丙种球蛋白血症的风险。然而，治疗期间的感染率仍然较低，且免疫球蛋白水平降低与感染发生率增加无关。
