From options to decisions: an innovative model for treatment sequencing in relapsing-remitting multiple sclerosis

With the expanding range of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS), clinicians face increasing complexity in defining optimal treatment sequences and timing of therapy switches. In this study, we adapted an earlier computer-assisted model to optimize therapeutic decisions and identify preferred treatment pathways, based on expert opinion and observations from clinical practice in Spain.

The original model was updated to integrate magnetic resonance imaging (MRI) activity data and define reaching an Expanded Disability Status Scale (EDSS) score of 3 - indicating moderate disability without ambulation impairment - as a criterion for switching treatment. Matrices were designed to model options when switching DMTs, triggered by either a lack of effectiveness or safety concerns. Change in DMT was based on a set of composite criteria (encompassing contributions from relapses, disability worsening, MRI activity, costs, and quality of life) according to the disease activity level. A maximum of three DMTs could be administered within the 8-year time horizon evaluated.

The revised model identified high efficacy treatment, in particular cladribine tablets as the preferred initial DMT for patients with RRMS with mild or moderate disease activity. Of these patients with mild and moderate disease activity, most were switched to ofatumumab (79.4%) and ocrelizumab (75.9%), respectively, when disease progression occurred. Patients with high disease activity mostly received natalizumab if they were John Cunningham virus (JCV)-negative, or ocrelizumab if they were JCV-positive.

The model is informed by a Spain-based healthcare expert panel and has been evaluated using a simulated cohort of 10,000 patients with RRMS.

This computational model helps to inform clinicians towards making optimal treatment decisions for RRMS, and identified high-efficacy DMTs as the preferred model-based option for all levels of disease activity, supporting early and effective control of disease activity in real-world clinical practice.