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

Clinical Snapshot

Key Findings

• P Value: Not applicable — decision-analytic modelling study; no inferential statistics reported

• Effect Size: Cladribine tablets identified as preferred initial DMT for mild and moderate disease activity; natalizumab preferred for JCV-negative high disease activity; ocrelizumab preferred for JCV-positive high disease activity

• Primary Outcome: Identification of preferred DMT sequences by disease activity level over an 8-year horizon in a simulated RRMS cohort of 10,000 patients

• Nnt Or Sensitivity: Not reported; no NNT, hazard ratios, or sensitivity/specificity metrics provided. Switch proportions reported: 79.4% of mild disease activity patients switched to ofatumumab; 75.9% of moderate disease activity patients switched to ocrelizumab on disease progression

• Confidence Interval: Not reported — no uncertainty quantification provided for model outputs

Clinical Application

The model concept is feasible as a clinical decision-support tool, but its current form lacks the transparency, validation, and uncertainty quantification required for direct clinical implementation. Adaptation to local formularies, patient populations, and healthcare system constraints would be necessary before use in practice Direct application to Australian practice is not appropriate without substantial recalibration. Key differences include: (1) PBS listing and authority prescription requirements for cladribine (Mavenclad), ocrelizumab (Ocrevus), ofatumumab (Kesimpta), and natalizumab (Tysabri) differ from Spanish formulary access; (2) TGA-approved indications and MSAC cost-effectiveness thresholds impose different access criteria; (3) MS Australia and MSAC have evaluated these agents under Australian-specific epidemiological and economic assumptions; (4) RACGP and the MS Research Australia guidelines emphasise shared decision-making and patient-centred care frameworks not explicitly incorporated in this model; (5) JCV testing and natalizumab risk stratification practices are consistent with Australian neurology practice, representing one transferable element Adults with RRMS across mild, moderate, and high disease activity strata, particularly those being considered for initial DMT selection or therapy switch due to inadequate response or safety concerns

Abstract

AIMS: 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. MATERIALS AND METHODS: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSION: 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.

References

1. 1.Oreja-Guevara, C., Landete, L., Rodriguez Sagrado, M. Á., Moya, I., Alcala Revilla, B., DelosSantos Real, H., Bernat Pinto, M. L., Harty, G., Fenwick, E., Sigworth, E., & Brieva Ruiz, L. (2026). From options to decisions: an innovative model for treatment sequencing in relapsing-remitting multiple sclerosis. Journal of Medical Economics. Advance online publication. https://doi.org/10.1080/13696998.2026.2688699