When Is the Optimal Time to Start Treatment in Patients With Relapsing-Remitting MS?
Real-world data identify when therapy initiation has the best chance of reducing long-term disability.
Neurology Reviews. 2018 November;26(11)
BERLIN—Data from the Big Multiple Sclerosis Data (BMSD) Network indicate that the optimal time to start disease-modifying therapy in patients with multiple sclerosis (MS) to prevent the long-term accumulation of disability is within six months of disease onset. This finding was presented by Pietro Iaffaldano, MD, and colleagues at ECTRIMS 2018. Dr. Iaffaldano is Assistant Professor of Neurology at the University of Bari, Italy.
Pietro Iaffaldano, MD
Many randomized clinical trials support the early start of disease-modifying therapies in MS. However, there is still an ongoing discussion on the optimal timing of treatment. For insight into this and other questions, the Danish, Italian, and Swedish national MS registries, MSBase, and the OFSEP of France pooled data for specific research projects in the BMSD Network. One question they sought to answer with this large, real-world data set was the optimal time to start disease-modifying therapy to prevent long-term disability accumulation in MS.
A cohort of patients with relapsing-remitting MS who had 10 or more years of follow-up, three or more years of cumulative disease-modifying therapy exposure, and three or more Expanded Disability Status Scale (EDSS) score evaluations was selected from the pooled cohort of the BMSD Network. The researchers conducted a set of pairwise (1:1) propensity score matching analyses with 10 different cut-offs for early versus delayed treatment (> 0.5 year up to > 5.0 years, using 0.5-year intervals) to allow an unbiased comparison between groups. The logistic model to predict propensity score included the following covariates: age at onset of the disease, sex, baseline EDSS, number of relapses in the two years before disease-modifying therapy start, number of EDSS evaluations, decade of birth, and registry source. To estimate the risk of reaching 12 months-confirmed EDSS progression (EDSSpr), a set of Cox models, adjusted for disease duration and relapses after disease-modifying therapy start as time-dependent covariates, was calculated.
A cohort of 11,871 patients with relapsing-remitting MS (71.0% female) was retrieved from the pooled BMSD Network database. The median (interquartile range) age at onset was 27.7 (22.3–34.6), median follow-up was 13.2 (11.4–15.4) years, and median time to the first disease-modifying therapy start was 3.8 (1.5–8.5) years. During the follow-up, an EDSSpr was reached by 4,138 (34.9%) patients. The lowest hazard ratio (HR) with relative 95% confidence interval (CI) for the propensity score matched models was obtained by a cutoff of treatment start within six months from disease onset (n = 873 per group). Early treatment significantly reduced the risk of reaching an EDSSpr (HR, 0.72 ). All subsequent comparisons between early and delayed treatment were not statistically significant.
This project was supported by Biogen International (Zug, Switzerland) on the basis of a sponsored research agreement with the BMSD Network.