Comparative effectiveness, persistence, and adherence of dimethyl fumarate and fingolimod in patients with multiple sclerosis in Japan: A cohort study

Background: 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. Methods: 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. Results: 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. Conclusion: 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.