OBJECTIVES: Fabry disease (FD) is a rare genetic disorder with approved treatments, including enzyme replacement therapies (agalsidase beta, agalsidase alfa, and pegunigalsidase alfa) or chaperone therapy (migalastat). Previously, comparative studies were conducted with agalsidase alfa or agalsidase beta; however, an NMA summarising all evidence has not been attempted. This study assessed the feasibility of conducting an NMA between agalsidase beta and other available treatments.

METHODS: A systematic literature review (SLR) was conducted to identify clinical evidence from January 2000–August 2022 on patients with FD. Seventeen outcomes of interest were explored, including composite endpoint, all-cause mortality, any renal/cardiac/cerebrovascular events, globotriaosylsphingosine level, e-GFR, left ventricular (LV) mass index (LVMI), LV posterior wall thickness, LV hypertrophy, interventricular septal thickness, Mainz Severity Score Index, brief pain inventory, EuroQol 5D, SF-36 survey, adverse events and discontinuations.

RESULTS: Among the 326 identified publications, 145 were included based on pre-defined inclusion criteria. Only randomised control trials (RCTs; n=14) and comparative non-RCTs (n=29) of any duration identified from the SLR were evaluated against the NMA feasibility assessment criteria. Further, only approved doses and studies reporting at least one outcome were considered. In total, 13 studies formed the best-case evidence network. LVMI was the only outcome that resulted in a connected network enabling comparisons across agalsidase beta, agalsidase alfa, and migalastat but with strong assumptions, including variations in the follow-up period (6 vs. 12 months) and LVMI measurement methods (MRI vs. echocardiogram) across studies. Thus, this analysis would have to assume a constant LVMI relative treatment effect and similarity between measurement methods.

CONCLUSIONS: Based on current evidence, an NMA comparing available treatment options for FD is not feasible due to heterogeneity among studies, especially on the outcomes included and/or their definition and/or time points evaluated. NMA may be feasible in the future if consistent evidence becomes available to construct a connected network.