1. In this prospective cohort study of patients with multiple sclerosis, upfront use of highly-efficacious disease modifying therapies (DMTs) compared with moderate intensity with escalation therapy was linked with a smaller change in disability score after 5-years.
2. Use of early intensive therapy was also demonstrated to have a longer time to sustained accumulation of disability.
Evidence Rating Level: 2 (Good)
Study Rundown: In the modern-era treatment of Multiple Sclerosis (MS) consists mainly of anti-inflammatory disease modifying therapies (DMTs). Currently the most efficacious DMTs are reserved for patients with high-risk features at diagnosis due to concerns of more associated adverse effects. The upfront use of the most efficacious DMTs (Early Intensive Therapy, EIT) has been suggested to manage the disease in its early, inflammatory phase to prevent long-term disability. The current study used data from a prospective MS cohort in order to evaluate whether a EIT strategy was more effective at slowing progression of disease-related disability than the traditional escalation therapy beginning with moderately efficacious DMTs. The study found that EIT was linked with less disability at 5 years and a longer time to sustained accumulated disability.
The main strength of the study includes its modern cohort, with prospectively collected data during a time period with modern therapy. The major limitations of the study include the moderate sample size and missing data.
In-Depth [prospective cohort]: This study used data from a population-based cohort of patients with MS living in southeast Wales, United Kingdom. Data was collected in a prospective fashion from 1998 to 2017. Patients in the cohort who were prescribed a DMT for MS were included in the study, while those participating in a clinical trial, treated at private clinics, or had insufficient data acquisition were excluded from the study. Highly efficacious DMTs included alemtuzumab and natalizumab, while moderately efficacious DMTs included interferons, glatiramer acetate, dimethyl fumarate, fingolimod, and teriflunomide. The primary outcome was change in 5-year in Expanded Disability Status Scale (EDSS) score and the secondary outcome was time to Sustained Accumulation of Disability (SAD) based off of sustained increased EDSS scores.
The study included 592 patients, of whom 104 received early intensive therapy. The EIT group had smaller change in EDSS at 5-years (0.3 [1.5] vs 1.2 [1.5], P=0.002), and longer median time to SAD: 6.0 (3.17-9.16) years for EIT and 3.14 (2.77-4.00) years for escalation therapy (P = 0.05).
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