T A Chalmer1,2, L M Baggesen3, M Nørgaard3, N Koch-Henriksen2,3, M Magyari1,2, P S Sorensen1,2. 1. Department of Neurology, Danish Multiple Sclerosis Center, Rigshospitalet, University of Copenhagen, Copenhagen. 2. Department of Neurology, The Danish Multiple Sclerosis Registry, Rigshospitalet, University of Copenhagen, Copenhagen. 3. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
Abstract
BACKGROUND AND PURPOSE: To assess long-term treatment effectiveness of disease-modifying therapy (DMT) initiated early in disease course versus later treatment start. METHODS: We included all Danish patients with multiple sclerosis (MS) treated with DMT through two nationwide population-based MS registries. Patients were categorized as early treated if treatment started within 2 years after the first MS symptom (n = 2316) and later treated if treatment started between 2 and 8 years after clinical onset (n = 1479). We compared time from treatment start to progression to an Expanded Disability Status Scale (EDSS) score of 6 and mortality between cohorts as hazard ratio (HR) using a Cox proportional hazards model with adjustment for stabilized inverse probability of treatment weights. Several sensitivity analyses were conducted. RESULTS: The median follow-up time of 3795 patients was 7.0 (range 0.6-19.5) years for the EDSS score of 6 outcome and 10.4 (range 1.2-20.1) years for the mortality outcome. Patients with later treatment start showed a 42% increased hazard rate of reaching an EDSS score of 6 compared with the early-treated patients [HR, 1.42; 95% confidence interval (CI), 1.18-1.70; P < 0.001]. When stratified by sex, the increased hazard among later-treated women persisted (HR, 1.53; 95% CI, 1.22-1.93; P < 0.001), whereas the HR was lower in men (1.25; 95% CI, 0.93-1.69; P = 0.15). Mortality was increased by 38% in later starters (HR, 1.38; 95% CI, 0.96-1.99; P = 0.08). CONCLUSIONS: Patients who started treatment with DMT later reached an EDSS score of 6 more quickly compared with patients who started early and the delay showed a tendency to shorten time to death. Our results support the use of early treatment.
BACKGROUND AND PURPOSE: To assess long-term treatment effectiveness of disease-modifying therapy (DMT) initiated early in disease course versus later treatment start. METHODS: We included all Danish patients with multiple sclerosis (MS) treated with DMT through two nationwide population-based MS registries. Patients were categorized as early treated if treatment started within 2 years after the first MS symptom (n = 2316) and later treated if treatment started between 2 and 8 years after clinical onset (n = 1479). We compared time from treatment start to progression to an Expanded Disability Status Scale (EDSS) score of 6 and mortality between cohorts as hazard ratio (HR) using a Cox proportional hazards model with adjustment for stabilized inverse probability of treatment weights. Several sensitivity analyses were conducted. RESULTS: The median follow-up time of 3795 patients was 7.0 (range 0.6-19.5) years for the EDSS score of 6 outcome and 10.4 (range 1.2-20.1) years for the mortality outcome. Patients with later treatment start showed a 42% increased hazard rate of reaching an EDSS score of 6 compared with the early-treated patients [HR, 1.42; 95% confidence interval (CI), 1.18-1.70; P < 0.001]. When stratified by sex, the increased hazard among later-treated women persisted (HR, 1.53; 95% CI, 1.22-1.93; P < 0.001), whereas the HR was lower in men (1.25; 95% CI, 0.93-1.69; P = 0.15). Mortality was increased by 38% in later starters (HR, 1.38; 95% CI, 0.96-1.99; P = 0.08). CONCLUSIONS:Patients who started treatment with DMT later reached an EDSS score of 6 more quickly compared with patients who started early and the delay showed a tendency to shorten time to death. Our results support the use of early treatment.
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