Shimazaki Sho, Fukasawa Toshiki, Kondo Takayuki, Takeuchi Masato, Okura Takayuki, Takahashi Ryosuke, Kawakami Koji
Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.
Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan; Department of Digital Health and Epidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.
Mult Scler Relat Disord. 2025 Feb;94:106306. doi: 10.1016/j.msard.2025.106306. Epub 2025 Jan 30.
Several oral disease-modifying drugs (DMDs) for multiple sclerosis (MS) are available but only two - dimethyl fumarate (DMF) and fingolimod (FTY) - are approved for relapsing-remitting MS in Japan. Although the efficacy of DMDs might be affected by differences in genetic and environmental factors, no study has compared the effectiveness, treatment persistence, and adherence of DMF and FTY in Asians. Here, we assessed relapse rates, persistence, and adherence of DMF and FTY in a Japanese real-world setting.
A cohort study was conducted using a large Japanese claims database. We included MS patients aged ≥18 years who initiated DMF or FTY between February 22, 2017 (the launch of DMF in Japan), and February 29, 2020. The primary effectiveness outcome was MS relapse, defined as treatment with intravenous methylprednisolone at a dosage of ≥250 mg/day for at least 3 consecutive days. Annualized relapse rates (ARRs) and ARR ratios for DMF and FTY groups were estimated using a Poisson regression model. Secondary outcomes included persistence and adherence. Persistence was evaluated using Kaplan-Meier survival analysis and a Cox proportional hazards model. Adherence was assessed by the proportion of days covered (PDC) at 30, 60, 90, 180, and 365 days. Propensity score overlap weighting was used to adjust for baseline covariates between groups.
143 patients in the DMF group (mean age 41.45 years, 59 males, mean number of MS relapses at baseline: 0.54) and 36 in the FTY group (mean age 39.89 years, 18 males, mean number of MS relapses at baseline: 0.56) met the eligibility criteria. After overlap weighting, covariates were well balanced. The ARR was 0.05 (95 % confidence interval, 0.02-0.16) in the DMF group and 0.15 (0.05-0.45) in the FTY group, with a ratio of 0.34 (0.07-1.63). The 1-year persistence was 0.84 (0.74-0.95) for the DMF group and 0.53 (0.37-0.78) for the FTY group, resulting in a hazard ratio of 0.28 (0.11-0.70). Median PDC for the DMF group was 0.90 (interquartile range, 0.77-1.00) at 30 days, which improved over time as treatment duration increased to reach 0.98 (0.94-0.98) at 365 days. In contrast, median PDC for the FTY group remained constant at 0.98-1.00 across all time points.
The effectiveness, as measured by ARRs, was comparable between the DMF and FTY groups, although a small but clinically significant difference may not have been detected in this study. Persistence was higher in the DMF group than in the FTY group. Adherence was high for both drugs, but some patients treated with DMF had low adherence early in treatment.
有几种用于治疗多发性硬化症（MS）的口服疾病修正药物（DMDs）可供使用，但在日本，只有两种药物——富马酸二甲酯（DMF）和芬戈莫德（FTY）——被批准用于复发缓解型MS。尽管DMDs的疗效可能会受到遗传和环境因素差异的影响，但尚无研究比较DMF和FTY在亚洲人中的有效性、治疗持续性和依从性。在此，我们在日本的真实世界环境中评估了DMF和FTY的复发率、持续性和依从性。
使用一个大型日本索赔数据库进行了一项队列研究。我们纳入了2017年2月22日（DMF在日本上市）至2020年2月29日期间开始使用DMF或FTY的年龄≥18岁的MS患者。主要有效性结局为MS复发，定义为连续至少3天接受剂量≥250mg/天的静脉注射甲泼尼龙治疗。使用泊松回归模型估计DMF组和FTY组的年化复发率（ARRs）和ARR比值。次要结局包括持续性和依从性。使用Kaplan-Meier生存分析和Cox比例风险模型评估持续性。通过30、60、90、180和365天时的覆盖天数比例（PDC）评估依从性。使用倾向得分重叠加权法调整组间的基线协变量。
DMF组有143例患者（平均年龄41.45岁，59例男性，基线时MS复发的平均次数：0.54），FTY组有36例患者（平均年龄39.89岁，18例男性，基线时MS复发 的平均次数：0.56）符合纳入标准。重叠加权后，协变量得到了很好的平衡。DMF组的ARR为0.05（95%置信区间，0.02 - 0.16），FTY组为0.15（0.05 - 0.45），比值为0.34（0.07 - 1.63）。DMF组的1年持续性为0.84（0.74 - 0.95），FTY组为0.53（0.37 - 0.78），风险比为0.28（0.11 - 0.70）。DMF组在30天时的PDC中位数为0.90（四分位间距，0.77 - 1.00），随着治疗时间的延长而改善，在365天时达到0.98（0.94 - 0.98）。相比之下，FTY组在所有时间点的PDC中位数均保持在0.98 - 1.00。
以ARRs衡量的有效性在DMF组和FTY组之间具有可比性，尽管在本研究中可能未检测到虽小但具有临床意义的差异。DMF组的持续性高于FTY组。两种药物 的依从性都很高，但一些接受DMF治疗的患者在治疗早期依从性较低。
