Analysis of the Italian cohort of late-onset Pompe disease (LOPD) patients after 10 and 15 years of therapy with alglucosidase alfa.

Abstract

Background and objectives: Late-onset Pompe disease (LOPD) is the first genetic neuromuscular disease treated with enzyme replacement therapy (ERT) in 2006, with variable results over time. This study aimed to assess therapeutic efficacy and safety in a large national cohort of patients after 10 and 15 years of treatment with alglucosidase alfa, all of them regularly evaluated in expert Centers.

Methods: This retrospective study analyzed data from 15 Italian Centers, examining clinical-genetic features and motor and respiratory outcomes at baseline, 10 years (T10, n = 85), and 15 years (T15, n = 42) after ERT initiation. Patients were categorized by baseline 6-min walk test (6MWT: 1: < 150 m, 2: 150-299 m, 3: 300-449 m, 4: ≥ 450 m) or forced vital capacity (FVC: 0: < 80%, 1: ≥ 80%) to assess outcome differences based on initial functional status.

Results: All patients were ambulant at baseline. Motor performance, assessed by 6MWT, declined across all functional groups, but even the lowest-performing patients at baseline (Groups 1-2) were mostly ambulant by T15 (50% and 71% respectively). In the best performing patients at baseline (Group 4), subjects maintained quite high performance values also at T15, with a statistically significant decrement observed at T10, and a stabilization at T15; none of them lost ambulation at T15. Despite an overall FVC% reduction, 21/42 patients (50%) remained ventilator-free at T15. No ERT discontinuations or significant adverse events were reported.

Conclusion: Alglucosidase alfa therapy showed variable results in a long-term perspective, confirming a reduction in mortality in all functional groups, and stabilization in several patients, without relevant safety concerns. Motor and respiratory function responses varied by functional groups and in single patients, underscoring the need for additional outcome measures. These long-term results will be useful for comparing the possible prolonged efficacy of the new therapies for Pompe disease.