AUTOPHAGIC MYOPATHIES / MYOFIBRILLAR MYOPATHIES / DISTAL MYOPATHIES / POMPE DISEASE: P.06 Long-term effects of enzyme replacement therapy in an elderly cohort of late-onset Pompe disease patients

Abstract

First longitudinal studies showed that enzyme replacement therapy (ERT) effects in late-onset Pompe disease (LOPD) seem to peak at 2-3 y often followed by a secondary decline. We aimed to examine long-term ERT effects in an elderly cohort of LOPD. Main inclusion criteria were age at diagnosis and onset of ERT > 50 y and ERT duration > 7 y. Outcome parameters included MRC sum-score (% of max.), 6-minute walk test 6MWT (% predicted), Quick Motor Function Test QMFT (% of max.), forced vital capacity FVC sitting and supine (% predicted), CK levels, and IgG antibody titers against alglucidase alfa. Six patients (3 f/3 m) qualified for the study, all were ambulatory at time of diagnosis. The median age at onset was 49 y (range 40-64), age at diagnosis and start of ERT 63 y (52-69), and age at last outcome 72.5 y (59-80). The median ERT duration was 8 y (7-12). Two patients became wheelchair-dependent. Two females were still able to walk unassisted and did not need noninvasive ventilation at the end of follow-up. There was no association between clinical outcome and genetic data, skeletal muscle histology, residual enzyme activity, and antibody titers. Peak antibody titers ranged from 0 to high with highest titers in best responders. Patients with lower ERT dosages had higher antibody titers. At least 50% of patients initially benefited from ERT. All patients showed a decline in FVC sitting during long-term follow-up, whereas 33% had a stabilization or improvement of FVC supine. 33% showed a stabilization or improvement of muscle strength. In contrast, QMFT deteriorated in 83% over time. However, 6MWT improved in 67% during a median ERT period of 8 y. CK levels continuously decreased in all patients. Best long-term results were seen in 6MWT, FVC supine and MRC sum-scores. Better ERT effects on FVC supine vs. sitting might hint to a preferential long-term effect on diaphragm muscles. In conclusion, ERT effects were heterogeneous but in general beneficial in elderly LOPD patients.