REAL-WORLD EVIDENCE REGARDING RENAL EFFECT OF MIGALASTAT

Migalastat effect on long-term renal outcomes in FD is not well defined. In 2021, a posthoc analysis of phase-3-clinical trials (FACETS/ATTRACT) and open-label extension (OLE) studies concluded that FD patients with “amenable” GLA variants receiving long-term Migalastat treatment maintained renal function irrespective of treatment status, gender or phenotype. Trials included "amenable" FD patients [enzyme replacement therapy (ERT)–naive and ERTexperience] receiving migalastat during >2years. In 2023, a posthoc analysis evaluated incidence of renal, cardiac and cerebrovascular events in FD adults and “amenable” GLA variants included in phase-III-clinical trials. Concluded that FD clinical events incidence in Migalastat-treated patients were low overall, comparable versus previous ERT trials. Aim: to review real-world publications regarding Migalastat renal effect in FD

Literature search in PubMed, EMBASE, SCOPUS and Cochrane data-bases. Term used: [Fabry disease and Migalastat and (renal or kidney)]. Prospective studies in which i)renal outcomes were the dependent variable or criterion, ii)FD patients receiving Migalastat during >6 months, were included. 2 researchers carried out the bibliographic search independently and another researcher carried out the final analysis to eliminate overlapping

PubMed (Inclusion Criteria: n=3), EMBASE (n=0), Scopus (n=0), Cochrane (n=0). Table 1 summarizes the manuscripts found. Müntze et al. analyzed a population with a mean age of 51.7±14.9 years, median glomerular filtration rate (GFR) of 85 mL/min/1.73m2 at baseline (T0). Males: GFR: 85(75–95) and 76(71–96)mL/min/1.73m2 at T0 and 12-moths respectively (p=0.042). Females: 110(76–90) and 106(70–89) mL/min/1.73m2 at T0 and 12-moths respectively (p=0.223). Reported difference between subgroup with previous ERT 95.5(84.3–108), 95(88.8–103.3)mL/min/1.73m2 at T0 and 12-moths respectively(p=0.607) and subgroup of therapy-naive 76(69–95), 72(65–78) mL/min/1.73m2 at T0 and 12-moths respectively (p=0.006). Subgroup with mutation N215S: 83.5 (75.3–89.3), 74.5 (71.3–90) mL/min/1.73m2 at T0 and 12-moths respectively (p=0.107). Riccio et al. reported that GFR It was stable (99.85±41.11and 98.28±40.46 mL/min/1.73m2 at T0 and 12-moths respectively) and proteinuria improve significantly (135.00±177.69 and 78.57±128.63 mg/24Hs. at T0 and 12-moths respectively) among FD males after switch from ERT. Renal adverse clinical events (end-points in this study) were not observed during follow-up. Lenders et al. reported results from a FD population (mean age 45±15 years), 61.1% previously treated with ERT and 57.4% suffered from arterial hypertension at T0. Females: GFR: 98.6±15.2 vs.90.4±14.7mL/min/1.73 m2(p=0.0317); males: GFR: 99.8±22.6 vs.92.4±24.0mL/min/1.73 m2(p=0.0028) at T0 and 24-months respectively. Albuminuria was stable during follow-up. Additional analysis showed that patients with cardiovascular risk factors and those receiving RAAS inhibitors drugs had a more prominent GFR drop

there is robust evidence from clinical trials and OLE regarding Migalastat renal benefits. In “real world data” the same trend is observed, although similar to that reported in patients treated with ERT: i) males or ii) with cardiovascular risk or iii) with low GFR at baseline or iv) simultaneously receiving RAASi may present more pronounced GFR drop