CORe, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
J Neurol Neurosurg Psychiatry. 2019 Apr;90(4):458-468. doi: 10.1136/jnnp-2018-319831. Epub 2019 Jan 13.
Oral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.
We identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).
The eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).
The effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.
口服免疫疗法已成为复发性多发性硬化症的标准治疗方法。需要直接比较它们对复发和残疾的影响。
我们在全球 MSBase 队列研究中确定了所有接受特立氟胺、二甲基富马酸酯或芬戈莫德治疗的复发性多发性硬化症患者,这些患者至少有 3 个月的治疗持续时间和残疾随访。使用倾向评分对患者进行匹配。通过负二项式模型和加权条件生存模型(带有成对 censoring)进行了三项两两分析,比较了年复发率和残疾累积、残疾改善和治疗中断的风险。
合格队列包括 614 例(特立氟胺)、782 例(二甲基富马酸酯)或 2332 例(芬戈莫德)患者,中位随访时间为 2.5 年。与特立氟胺(0.18 比 0.24;p=0.05)和二甲基富马酸酯(0.20 比 0.26;p=0.01)相比,芬戈莫德的年复发率较低,而特立氟胺和二甲基富马酸酯的年复发率相似(0.19 比 0.22;p=0.55)。在残疾累积(p≥0.59)或改善(p≥0.14)方面,三种治疗方法之间没有差异。在≥3 个月治疗持续时间的患者中,与特立氟胺和二甲基富马酸酯相比,芬戈莫德随后停药的可能性较小(p<0.001)。特立氟胺和二甲基富马酸酯的停药率相似(p=0.68)。
与特立氟胺和二甲基富马酸酯相比,芬戈莫德对复发频率的影响更优。在最初 2.5 年的治疗期间,三种口服疗法对残疾结局的影响相似。与两种对照药物相比,芬戈莫德的持久性更优。