Comparative Effectiveness of Disease-Modifying Therapies in Relapsing-Remitting Multiple Sclerosis

Relapsing-remitting multiple sclerosis (RRMS) is characterised by episodes of neurological dysfunction followed by periods of partial or complete recovery. Over the past two decades, the introduction of disease-modifying therapies (DMTs) has shifted treatment goals from simply reducing relapse frequency to achieving sustained remission of inflammatory activity. High-efficacy agents such as monoclonal antibodies, including natalizumab and ocrelizumab, compete with oral immunomodulators such as fingolimod and teriflunomide. Clinicians now weigh individual risk–benefit profiles, considering not only annualised relapse rates and disability progression but also safety, tolerability and cost. Comparative effectiveness studies—ranging from head-to-head observational cohorts to network meta-analyses—have elucidated that monoclonal antibodies often deliver superior relapse suppression and higher proportions of patients attaining no evidence of disease activity (NEDA-3) over two to four years. However, oral agents retain advantages in convenience and safety monitoring, and emerging precision-medicine approaches aim to predict optimal responders. The global challenge remains to integrate real-world data with randomised trial outcomes, adapt to regional healthcare infrastructures and tailor therapy to minimise both clinical and radiological disease activity while preserving long-term neurological function.

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Comparative Effectiveness of Disease-Modifying Therapies in Relapsing-Remitting Multiple Sclerosis publication trend

The graph below shows the total number of articles in comparative effectiveness of disease-modifying therapies in relapsing-remitting multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

Disease-modifying therapies (DMTs): Treatments intended to alter the underlying pathological course of multiple sclerosis, reducing relapse frequency and slowing disability progression.

Relapsing-remitting multiple sclerosis (RRMS): A form of MS marked by episodes of neurological dysfunction (relapses) followed by periods of recovery (remissions).

Annualised relapse rate (ARR): The average number of clinical relapses experienced by a patient per year of follow-up.

Expanded Disability Status Scale (EDSS): A scale ranging from 0 to 10 that quantifies neurological impairment and disability in MS.

No evidence of disease activity (NEDA-3): A composite outcome defined by absence of relapses, no sustained EDSS progression and no new or enlarging lesions on magnetic resonance imaging.

References

1. A two-years real-word study with fingolimod: early predictors of efficacy and an association between EBNA-1 IgG titers and multiple sclerosis progression. Frontiers in Immunology (2024).
2. Long-term comparative analysis of no evidence of disease activity (NEDA-3) status between multiple sclerosis patients treated with natalizumab and fingolimod for up to 4 years. Neurological Sciences (2021).
3. The Efficacy of Natalizumab versus Fingolimod for Patients with Relapsing-Remitting Multiple Sclerosis: A Systematic Review, Indirect Evidence from Randomized Placebo-Controlled Trials and Meta-Analysis of Observational Head-to-Head Trials. PLOS ONE (2016).