OBJECTIVES: Fabry disease (FD) is a rare, chronic, slowly progressing multisystem disorder. Prevention of renal, cardiovascular, and cerebrovascular events (ie, Fabry clinical events; FCEs) is the main treatment goal. Because such events are challenging to track given the limited timeframes of clinical studies, a holistic measurement tool covering all three domains of interest and providing long-term outcome prediction would be valuable. The Mainz Severity Score Index (MSSI) constitutes a promising endpoint in FD because it considers general, neurological, cardiovascular, and renal signs and symptoms and score changes are seen shortly after starting treatment. Currently, its predictive value for FCEs in FD is not well established. The present study was aimed at investigating MSSI-to-FCE relationship in FD.

METHODS: A targeted literature review was conducted, and any available relationships between MSSI and FCEs were extracted. The data were analyzed to determine the availability of predictive tools.

RESULTS: Ten studies met the inclusion criteria. All studies used observational data including some cohort data. The maximum follow-up time was 15 years. The relationship of MSSI with cardiac, renal, and cerebral events was investigated in 70% (7/10), 50% (5/10), and 20% (2/10) of studies, respectively. One study established a MSSI score ≥18 as a cut-off to predict a poor renal prognosis. Predictive models using multivariate regression analyses were presented in four studies including other treatment effect modifiers like age and sex, in addition to MSSI.

CONCLUSIONS: To our knowledge, this is the first literature review of studies that investigated MSSI-to-FCE relationships in FD. Currently, evidence supporting MSSI as a surrogate endpoint is insufficient, given the paucity of studies, existing study design, small sample sizes, and heterogeneity in the events explored. Additional studies would be required to explore the correlation further and offer a predictive tool useful for health economic modeling in FD.