Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå.
Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, University Hospital Solna, Stockholm.
Eur J Neurol. 2019 Aug;26(8):1060-1067. doi: 10.1111/ene.13936. Epub 2019 Mar 12.
Breakthrough disease on first-line injectables in relapsing-remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS.
Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder-adjusted Cox proportional hazard models.
A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2-5.6) for RTX and 3.4 (95% CI, 1.3-9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01-0.38) for RTX and 1.0 (95% CI, 0.6-1.7) for FGL vs. NTZ.
In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.
在复发缓解型多发性硬化症（RRMS）中，一线注射剂突破性疾病是一种常见的临床情况，缺乏不同升级治疗方案的比较研究。本研究旨在比较那他珠单抗（NTZ）、利妥昔单抗（RTX）和芬戈莫德（FGL）作为 RRMS 升级治疗的疗效、安全性和药物维持率。
通过在四家大型多发性硬化症（MS）中心的瑞典 MS 注册处，对因突破性疾病而从干扰素或聚乙二醇干扰素转为 NTZ、RTX 或 FGL 的患者进行回顾性观察研究。数据来自 MS 注册处和病历。使用多变量混杂因素调整后的 Cox 比例风险模型计算复发、不良事件和药物停药的风险比（HR）及其 95%置信区间（CI）。
共纳入 241 例患者。NTZ、RTX 和 FGL 的年复发率分别为 0.02、0.03 和 0.07。与 NTZ 相比，RTX 的调整后 HR 为 1.0（95%CI，0.2-5.6），FGL 为 3.4（95%CI，1.3-9.2）。NTZ、RTX 和 FGL 的年药物停药率分别为 0.15、0.01 和 0.15。RTX 的调整后 HR 为 0.05（95%CI，0.01-0.38），FGL 为 1.0（95%CI，0.6-1.7），均优于 NTZ。
在干扰素/聚乙二醇干扰素治疗的 RRMS 患者中，出现突破性疾病时，转为 NTZ 或 RTX 与 FGL 相比疾病活动度较低。与 NTZ 和 FGL 相比，RTX 显示出更好的药物维持率。
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