The impact of interrupting enzyme replacement therapy in late‑onset Pompe disease

J Neurol. 2021 Feb 24;1-8. doi: 10.1007/s00415-021-10475-z. Online ahead of print.

PMID: 33625582

Stephan Wenninger · Kristina Gutschmidt · Corinna Wirner · Krisztina Einvag · Federica Montagnese · Benedikt Schoser

Summary: This study aimed to analyse the impact of ERT interruption on clinical outcome of LOPD patients. As a result, interruption of ERT was associated with a worsening of the objective outcome measures. Therefore, an interruption of ERT in LOPD should be kept as short as possible.

Abstract

Objective: Late-onset Pompe disease (LOPD) causes progressive weakness of locomotor and respiratory muscles. Enzyme replacement therapy (ERT), administered biweekly, slows down disease progression and stabilize pulmonary function. Due to the COVID-19 pandemic, ERT was interrupted at one centre in Germany for 29 days. This study aimed to analyse the impact of ERT interruption on clinical outcome of LOPD patients.

Methods: This was a prospective cohort study. 12 LOPD patients were included to the study. Clinical evaluations were carried out after the ERT was stopped and after the next three consecutive infusions. Motor function is assessed by muscle strength testing, a 6-minute-walk-test, pulmonary function tests, and adverse events. Based on the individual yearly decrease, an estimated baseline was determined for statistical analysis.

Results: The mean time of ERT interruption was 49.42 days (SD ± 12.54). Seven patients reported 14 adverse events, two of which were severe, during the ERT interruption. Common adverse events were reduced muscle endurance/increased muscle fatigability and shortness of breath/worsening of breathing impairment. MIP%pred (maximal inspiratory pressure), MRC%pred (Medical Research Council grading scale used to determine the skeletal muscle strength), FVC%pred (forced vital capacity) and 6MWT%pred (6-minute-walk-test), all showed significant deterioration after ERT interruption. (Values are presented as % of predicted.)

Conclusion: Interruption of ERT was associated with a worsening of the objective outcome measures and an increased rate of adverse events. Therefore, an interruption of ERT in LOPD should be avoided or kept as short as possible.