Economic evaluations of disease-modifying therapies for spinal muscular atrophy: a systematic literature review

TL;DR

This paper reviews studies on the cost-effectiveness of new spinal muscular atrophy treatments, highlighting challenges due to high costs and limited long-term data.

Contribution

The study provides a systematic review of economic evaluations for SMA therapies, identifying methodological gaps and suggesting improvements for future research.

Findings

21 studies were included, all using Markov models with varying assumptions about treatment benefits and survival.

Treatment costs and health-state utility values were key drivers of cost-effectiveness, but data sources and methods were inconsistent.

Short-term clinical data and lack of transparency in modeling limited the robustness of findings across studies.

Abstract

Spinal muscular atrophy (SMA) is a rare, life-limiting neuromuscular disorder characterised by progressive motor neuron degeneration. The recent emergence of disease-modifying therapies (DMTs), nusinersen, onasemnogene abeparvovec, and risdiplam, has revolutionised SMA care but presents economic challenges due to high treatment costs and limited long-term evidence.

To review and critically appraise economic evaluations that assessed the cost-effectiveness of DMTs in people living with SMA.

A systematic literature review was conducted following Cochrane and PRISMA guidelines. Initial searches were conducted in January 2024 and updated in February 2025. Searches were carried out in key biomedical and economic databases, as well as grey literature. Two reviewers independently screened the titles and abstracts of all identified records, as well as the full texts of potentially relevant studies. Data extraction and quality appraisal employed established tools, including the CHEERS and Philips checklists. The conduct and findings of included studies were summarised and discussed narratively.

Of 1,984 records, 21 studies met the inclusion criteria. All studies used Markov modelling approaches, varying by SMA type, time horizon (often lifetime), and assumptions around sustained treatment benefits. Key drivers of cost-effectiveness included treatment costs, health-state utility values (frequently based on expert opinion), and survival modelling. Heterogeneity was noted in health technology definitions, utility measurement, and data sources. Limitations across studies included reliance on short-term clinical data, inconsistent assumptions, and limited of transparency in modelling practices. Sensitivity analyses were inconsistently applied, limiting robustness of the findings reported in each study.

The economic evaluation landscape for SMA treatments is evolving. However, challenges remain due to data gaps and methodological variability across studies. Future research should prioritise the integration of long-term real-world data into economic evaluations, consider the development of patient- and caregiver-derived utility values, and the use of transparent, standardised modelling approaches. These improvements will enhance the robustness, comparability, and policy relevance of economic evaluations in rare disease treatment funding.

The online version contains supplementary material available at 10.1186/s13023-025-04150-z.

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