Authors: Lara Mohammed Aljohani , Dimah Jalal Alsarrawi , Raghad Mohammed Zayed , Shahd Abdullah Almutairi , Ruof Saadallah Alzahrani , Shaden Sultan Almutiri , Ola Obeid Taha , Sama Abdullah Alanazi , Waqar Ali

Abstract

Background: Relapsing-remitting multiple sclerosis is a chronic immune-mediated disorder of the central nervous system associated with recurrent inflammatory activity and long-term disability accumulation. Although escalation therapy has traditionally been used, early initiation of high-efficacy disease-modifying therapies may provide stronger inflammatory control and improve long-term outcomes.

Objective: This systematic review and meta-analysis aimed to compare early initiation of high-efficacy disease-modifying therapies with escalation or delayed treatment strategies in adults with relapsing-remitting multiple sclerosis.

Methods: PubMed, Scopus, and Web of Science were systematically searched. Eligible studies included adults with relapsing-remitting multiple sclerosis treated with either early high-efficacy disease-modifying therapies or escalation/delayed strategies. Outcomes included annualized relapse rate, Expanded Disability Status Scale change, and delta-Expanded Disability Status Scale. Study quality was assessed using the Newcastle-Ottawa Scale, and pooled analyses were performed using random-effects models.

Results: Ten observational cohort studies were included. Early initiation of high-efficacy treatment was associated with lower annualized relapse rate than escalation therapy. Disability findings remained uncertain. The pooled EDSS-change analysis was not statistically significant and showed considerable heterogeneity. Only one eligible study reported an adjusted delta-EDSS comparison; therefore, this outcome was reported narratively and was not meta-analyzed. Nonrandom treatment allocation and potential confounding by indication limit causal interpretation.

Conclusion: Early initiation of high-efficacy disease-modifying therapy was associated with lower relapse activity in observational RRMS cohorts. The available disability evidence does not establish a causal advantage of either treatment strategy and requires cautious interpretation.

Keywords: Relapsing-remitting multiple sclerosis, high-efficacy disease-modifying therapy, early intensive treatment, escalation therapy, meta-analysis.