Derfuss Tobias, Bermel Robert, Lin Chien-Ju, Hauser Stephen L, Kappos Ludwig, Vollmer Timothy, Comi Giancarlo, Giovannoni Gavin, Hartung Hans-Peter, Weber Martin S, Wang Jianmei, Jessop Nikki, Chognot Cathy, Craveiro Licinio, Bar-Or Amit
Department of Neurology, University Hospital Basel, University of Basel, Hebelstrasse 20, Basel 4031, Switzerland.
Mellen Center for MS, Cleveland Clinic, Cleveland, OH, USA.
Ther Adv Neurol Disord. 2024 Oct 8;17:17562864241277736. doi: 10.1177/17562864241277736. eCollection 2024.
Patients with multiple sclerosis (PwMS) have an increased risk of infections.
To characterize incidence, clinical characteristics, outcomes and risk factors of infections, and serious infections (SIs) in ocrelizumab (OCR)-treated PwMS.
analysis of pooled data from 6155 patients in 13 clinical trials.
Descriptive analyses of clinical characteristics and outcomes were reported over ⩽14 years. A Poisson Generalized Estimating Equation model was constructed to examine risk factors in a subgroup of patients with longer exposure to OCR ( = 2092).
Over a median (max) treatment period of 3.7 (13.9) years, 420/6155 patients (6.8%) experienced 583 SIs, excluding coronavirus disease 2019. Incidence rates in relapsing multiple sclerosis (RMS; 1.50 per 100 patient years [95% confidence interval (CI): 1.34-1.68]) and progressive multiple sclerosis (PMS; 3.70 [95% CI: 3.27-4.17]) remained stable over this period. Lower respiratory tract, urinary tract, abdominal and gastrointestinal, and skin infections were the most commonly reported SIs. Most SIs (~90%) resolved, and treatment with OCR was continued in >80% of cases. The presence of 1 or ⩾2 comorbidities (rate ratio = 1.66, 2.73, respectively), recent relapse activity (2.06), and Expanded Disability Status Scale (EDSS) score ⩾6.0 (2.02) were significant risk factors for SIs in patients with RMS treated over a median (max) period of 8.3 (11.2) years. In patients with primary PMS treated over a median (max) period of 7.1 (11.8) years, an EDSS score ⩾6.0 was associated with the greatest risk of SIs, a 4-fold increase (rate ratio, 4.31), followed by abnormal immunoglobulin (Ig)M levels (1.89), the presence of ⩾2 comorbidities (1.80), and having overweight/obesity (1.46). Time on OCR and abnormal IgG levels were not significantly associated with an increased SI risk.
Continuous long-term treatment with OCR is associated with a manageable infection risk profile. Optimal disease control and addressing modifiable risk factors may reduce the risk of infections.
多发性硬化症患者（PwMS）感染风险增加。
描述接受奥瑞珠单抗（OCR）治疗的PwMS患者感染及严重感染（SI）的发生率、临床特征、结局和危险因素。
对13项临床试验中6155例患者的汇总数据进行分析。
报告了⩽14年期间临床特征和结局的描述性分析。构建泊松广义估计方程模型，以检查OCR暴露时间较长的患者亚组（n = 2092）中的危险因素。
在中位（最长）治疗期3.7（13.9）年期间，420/6155例患者（6.8%）发生了583次SI，不包括2019冠状病毒病。复发型多发性硬化症（RMS；每100患者年1.50次[95%置信区间（CI）：1.34 - 1.68]）和进展型多发性硬化症（PMS；3.70 [95% CI：3.27 - 4.17]）的发生率在此期间保持稳定。下呼吸道、泌尿道、腹部和胃肠道以及皮肤感染是最常报告的SI。大多数SI（~90%）得到缓解，超过80%的病例继续使用OCR治疗。在中位（最长）8.3（11.2）年期间接受治疗的RMS患者中，存在1种或⩾2种合并症（发生率比分别为1.66、2.73）、近期复发活动（2.06）以及扩展残疾状态量表（EDSS）评分⩾6.0（2.02）是SI的显著危险因素。在中位（最长）7.1（11.8）年期间接受治疗的原发性PMS患者中，EDSS评分⩾6.0与SI风险最高相关，增加了4倍（发生率比，4.31），其次是免疫球蛋白（Ig）M水平异常（1.89）、存在⩾2种合并症（1.80）以及超重/肥胖（1.46）。使用OCR的时间和IgG水平异常与SI风险增加无显著关联。
持续长期使用OCR与可控的感染风险特征相关。优化疾病控制并解决可改变的危险因素可能会降低感染风险。
