OBJECTIVES: Patients with Fabry disease (FD), a rare metabolic disorder, present high heterogeneity in disease characteristics. With no interventional studies directly comparing treatments, it is important for indirect treatment comparisons (ITCs) to consider potential effect modifiers (EMs). We conducted a systematic literature review (SLR) of real-world evidence (RWE) in FD to identify patient characteristics which may impact clinical outcomes

METHODS: An SLR was conducted using PRISMA guidelines by searching EMBASE, MEDLINE, and Cochrane databases (1946 through the search date of 1 August 2022) for full-text articles reporting clinical outcomes of RWE studies of pharmacological therapies for the treatment of FD.

RESULTS: A total of 940 publications were identified. Of these, 92 original studies fulfilled the PICOS criteria. Several potential EMs in FD were identified: gender, age, early/delayed treatment, left ventricular hypertrophy (LVH), estimated glomerular filtration rate (eGFR), proteinuria, baseline presence of anti-drug-antibodies (ADAs), and prior enzyme replacement therapy (ERT). In two studies of ERT-treated patients, males presented worse renal outcomes than females. Four studies found both younger patients and those who received initial ERT before age 25 years experienced greater reductions in plasma-lysoGb3 and more favorable renal, cardiac, and biochemical outcomes. Three studies reported associations between LVH and reduced eGFR at baseline, and increased risk of cardiovascular, renal, and neurological events. Reduced eGFR and proteinuria were linked to faster annual eGFR decline despite ERT in two studies each; high baseline proteinuria was a significant indicator of renal disease progression. Baseline ADAs were associated with reduced treatment impact on plasma/urine-lysoGb3. Migalastat was effective in treatment-naïve patients whereas deteriorations in mean lysoGb3, eGFR, and left ventricular mass were observed in the prior-ERT group.

CONCLUSIONS: This SLR identified several patient characteristics that impact the effectiveness of treatments in FD. Adjustments for these characteristics should be considered during ITCs to ensure un-biased outcomes