Rød Brit Ellen, Høgestøl Einar A, Torkildsen Øivind, Bjørnevik Kjetil, Gran Jon Michael, Øverås Mathias H, König Marton, Myhr Kjell-Morten, Wergeland Stig, Nygaard Gro O
Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Mult Scler. 2025 Jul;31(8):975-984. doi: 10.1177/13524585251342727. Epub 2025 May 26.
Head-to-head comparisons of high-efficacy therapies for relapsing-remitting multiple sclerosis (RRMS) are lacking. We conducted a target trial emulation to compare the long-term effectiveness of rituximab and cladribine.
We estimated the effect of initiating treatment with rituximab versus cladribine using observational data from the Norwegian MS Registry and Biobank at two university hospitals with different treatment strategies. Cumulative incidence and risk differences (RDs) were estimated using weighted Kaplan-Meier estimators, adjusting for baseline covariates. The primary outcome was magnetic resonance imaging (MRI) disease activity, with secondary outcomes including relapses and safety.
The study included 285 patients, 159 receiving rituximab and 126 cladribine, with a median follow-up of 4.5 years (interquartile range (IQR): 4.2-4.7). The 4-year risk of new MRI disease activity was 17% (95% confidence interval (CI): 11-23) for rituximab-treated patients and 57% (95% CI: 44-66) for cladribine-treated patients, yielding an RD of 40 percentage-points (95% CI: 28-50). The 4-year RD for relapse was 12 percentage-points (95% CI: 4-19). The incidence of hospitalizations related to potential adverse events was 6.0 per 100 person-years for rituximab and 4 per 100 person-years for cladribine.
These findings suggest that rituximab has superior effectiveness compared to cladribine during a median follow-up of 4.5 years.
缺乏针对复发缓解型多发性硬化症（RRMS）的高效疗法的直接对比研究。我们进行了一项目标试验模拟，以比较利妥昔单抗和克拉屈滨的长期疗效。
我们利用挪威多发性硬化症登记处和生物样本库在两家采用不同治疗策略的大学医院的观察性数据，估算了起始使用利妥昔单抗与克拉屈滨治疗的效果。使用加权Kaplan-Meier估计量估计累积发病率和风险差异（RDs），并对基线协变量进行调整。主要结局是磁共振成像（MRI）疾病活动，次要结局包括复发和安全性。
该研究纳入了285例患者，159例接受利妥昔单抗治疗，126例接受克拉屈滨治疗，中位随访时间为4.5年（四分位间距（IQR）：4.2 - 4.7）。接受利妥昔单抗治疗的患者4年出现新的MRI疾病活动的风险为17%（95%置信区间（CI）：11 - 23），接受克拉屈滨治疗的患者为57%（95% CI：44 - 66），风险差异为40个百分点（95% CI：28 - 50）。4年复发的风险差异为12个百分点（95% CI：4 - 19）。与潜在不良事件相关的住院发生率，利妥昔单抗为每100人年6.0次，克拉屈滨为每100人年4次。
这些发现表明，在4.5年的中位随访期内，利妥昔单抗的疗效优于克拉屈滨。
