Davies Laura, Shehadeh Rasheed, Watkins W John, Jolles Stephen, Robertson Neil P, Tallantyre Emma C
Helen Durham Neuro-Inflammatory Unit, University Hospital of Wales, Cardiff, CF14 4XW, UK.
School of Medicine, Cardiff University, Cardiff, UK.
J Neurol. 2025 May 22;272(6):415. doi: 10.1007/s00415-025-13133-w.
Anti-CD20 monoclonal antibodies are now a common first-line treatment for multiple sclerosis (MS). Rituximab, ocrelizumab and ofatumumab have all been associated with a dose-dependent risk of hypogammaglobulinaemia, but its relevance in clinical practice remains uncertain.
To study infection rates over time in a real-world cohort of people treated with ocrelizumab for MS, and their relationship to serum immunoglobulin.
Observational study of 152 people receiving ocrelizumab for MS followed for up to 5.6 years (mean 2.7 years).
Mean (SD) annualized changes in immunoglobulins during ocrelizumab treatment were IgM - 0.22 g/L/year (0.4), IgG - 0.38 g/L/year (0.9), IgA - 0.03 g/L/year. Rates of self-reported infection increased significantly during the first 4 years of treatment. Infection rates were not only associated with total immunoglobulin levels but also independently associated with age, comorbidity and female sex. We demonstrated for the first time that 29 out of 34 (87%) people on ocrelizumab with IgG in the lower normal range had sub-protective antibody responses to pneumococcus / haemophilus influenzae.
Real-world observational studies complement open label extensions of clinical trials, often by having a more representative cohort and more complete follow-up. Our data suggest that while serious infections are rare in people on ocrelizumab, non-serious infections become increasingly burdensome. We offer practical suggestions on mitigating the risk of infection on ocrelizumab and other anti-CD20 medications.
抗CD20单克隆抗体现已成为多发性硬化症（MS）常见的一线治疗药物。利妥昔单抗、奥瑞珠单抗和奥法木单抗均与剂量依赖性低丙种球蛋白血症风险相关，但其在临床实践中的相关性仍不确定。
研究在接受奥瑞珠单抗治疗MS的真实世界队列中随时间推移的感染率，以及它们与血清免疫球蛋白的关系。
对152例接受奥瑞珠单抗治疗MS的患者进行观察性研究，随访长达5.6年（平均2.7年）。
奥瑞珠单抗治疗期间免疫球蛋白的平均（标准差）年化变化为：IgM - 0.22g/L/年（0.4），IgG - 0.38g/L/年（0.9），IgA - 0.03g/L/年。在治疗的前4年中，自我报告的感染率显著增加。感染率不仅与总免疫球蛋白水平相关，还与年龄、合并症和女性性别独立相关。我们首次证明，34例接受奥瑞珠单抗治疗且IgG处于正常范围下限的患者中，有29例（87%）对肺炎球菌/流感嗜血杆菌的抗体反应不足。
真实世界观察性研究补充了临床试验的开放标签扩展研究，通常具有更具代表性的队列和更完整的随访。我们的数据表明，虽然接受奥瑞珠单抗治疗的患者中严重感染很少见，但非严重感染的负担越来越重。我们针对降低使用奥瑞珠单抗和其他抗CD20药物时的感染风险提供了实用建议。
