Predictors of initiating high-efficacy vs. platform therapies as first-line disease-modifying treatment in multiple...

The therapeutic landscape of multiple sclerosis (MS) is rapidly evolving, with increasing emphasis on early initiation of high-efficacy disease-modifying therapies (heDMTs). However, real-world data on predictors of first-line heDMT use and its outcomes remain scarce in the Middle East.

To identify demographic and clinical factors influencing the choice of first-line heDMT vs. platform therapy in relapsing-remitting MS (RRMS) and to evaluate whether initial treatment class impacts disability outcomes and treatment persistence.

We conducted a retrospective cohort study of 826 RRMS patients treated at a tertiary center in Saudi Arabia between 2016 and 2024. Predictors of initiating heDMT were identified using multivariable logistic regression. Disability status (EDSS category) was analyzed using ordinal logistic regression. Treatment persistence and causes of discontinuation were examined using Kaplan-Meier survival analysis, Cox proportional hazards modeling, and Fine-Gray competing-risks regression.

Of 826 patients, 330 (40%) received heDMTs as first-line therapy. Initiation in the later treatment era (2019-2024) strongly predicted heDMT use compared with the early treatment era (2008-2013; OR = 48.8; p < 0.001), as did cerebellar symptom onset (OR = 2.51; p = 0.025). Age, sex, and comorbidities were not significant predictors. Starting on a heDMT did not translate into higher or lower disability levels compared with platform therapies (OR = 1.08; p = 0.767). However, patients initiating heDMTs demonstrated superior treatment persistence (12-month persistence: 91.7 vs. 83.4%; p < 0.0001) and a markedly lower risk of discontinuation (HR = 0.41; p < 0.001). Competing-risks analysis showed that heDMT users were significantly less likely to discontinue due to inefficacy or adverse events, but more likely to stop for other reasons, such as pregnancy, preference, or supply issues.

First-line use of heDMTs in Saudi Arabia has increased substantially over recent years, particularly among patients with cerebellar onset. While disability outcomes were similar between treatment groups, initiating heDMTs conferred clear advantages in persistence and tolerability. These findings reinforce the paradigm shift toward early intensive MS management and highlight the need for broader access and guideline-driven implementation of heDMTs in the region.