Early versus Later Treatment Start in Multiple Sclerosis - A Register Based Cohort Study (S8.007)

Objective: To assess long-term effects of disease-modifying therapy (DMT) initiated early in the disease course compared with later treatment start.

Background: The timing of DMT in patients with multiple sclerosis is assumed to be important for the time to reach confirmed disease worsening and the time to reach death. Observational studies based on nationwide registries are ideal to investigate treatment effectiveness in a real world population.

Design/Methods: We retrieved data on all Danish MS patients (n=3,795) treated with DMT from two nationwide population based MS registries. The cohort consisted of early treated patients, defined as treatment start within two years after the first MS symptom (n=2,316) and later treated patients, defined as treatment start between two and eight years from clinical onset (n=1,479). We compared time to progression to Expanded Disability Status Scale (EDSS) 6 and mortality between cohorts as hazard ratio (HR) using a Cox proportional hazards model with adjustment for inverse probability of treatment weights. Several sensitivity analyses were conducted.

Results: Median follow-up time was 10 years for both the EDSS 6 outcome (range 1–20) and mortality. Patients with later treatment start showed 28% increased hazard of reaching EDSS 6 compared with the early treated patients (HR 1.28; 95% CI 1.12–1.45). When stratified by sex the increased hazard among later treated women persisted (HR 1.39; 95% CI 1.19–1.63), while the HR decreased in men (1.09; 95% CI 0.89–1.35). Regarding mortality HR did not differ between early and later treatment start (HR 1.02; 95% CI 0.71–1.47).

Conclusions: Patients who started treatment with DMT late had shorter time to reaching EDSS 6 compared with patients who started early, but the delay did not influence mortality. Our results support the scheme of early treatment.

Study Supported by: This study was supported by The Danish Multiple Sclerosis Society; Foundation for Research in Neurology; Gangstefonden; Ejnar Jonassons called Johnsen and wife’s memorial fund.

Disclosure: Dr. Chalmer has received research support from received support for congress participation from Roche (ECTRIMS 2016) and Merck (ECTRIMS 2017). Dr. Magyari has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Sanofi, Teva, Roche, Novartis, Merck. Dr. Magyari has received research support from received support for congress participation from Biogen, Genzyme, Teva, Roche. Dr. Baggesen has nothing to disclose. Dr. Nørgaard has nothing to disclose. Dr. Koch-Henriksen has received research support from Travel expenses, accommodation, and congressional fees from Merck for participation to the 2017 ECTRIMS congress. Dr. Sorensen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Merck, Novartis, TEVA, GlaxoSmithKline, medDay Pharmaceuticals, Celgene, Genzyme, Novartis and Forward.