Break in ERT Treatment Linked to Worse Outcomes in Late-Onset Pompe Patients, Study Reports

Long-term interruption of enzyme replacement therapy (ERT) can lead to negative outcomes for late-onset Pompe disease patients, affecting their lung and exercise capacity as well as quality of life, a Swiss retrospective study shows.

However, for most patients, resuming ERT can help restore the key clinical parameters that deteriorated during the pause in treatment.

The study, “36-Months follow-up assessment after cessation and resuming of enzyme replacement therapy in late onset Pompe disease: data from the Swiss Pompe Registry,” was published in the Journal of Neurology.

Lack of human alpha-glucosidase (GAA) is the underlying cause of Pompe disease. ERT using a recombinant (lab-made) GAA stabilizes patients’ respiratory function, improves their exercise tolerance, and increases their overall survival.

ERT, however, is not curative, meaning that patients may require long-term treatment, which is linked to high costs. In Switzerland, eligibility for ERT and reimbursement for therapy costs rfollow strict criteria.

Due to a Swiss Federal Supreme Court decision on ERT reimbursement, a specific group of patients remained without access to ERT for a time period that varied between 3.1 and 59.3 months.

A team of researchers studied this group of patients to assess the long-term clinical effects of stopping and restarting treatment with ERT.

In total, the study included seven female patients with genetically and enzymatically confirmed late-onset Pompe disease.

Patients had received treatment with Myozyme (alglucosidase alfa) at a dose of 20 mg per kilogram of body weight every other week, for a mean period between 3.1 to 61.3 months, before the court decision. After resuming treatment, they were followed for 36 months.

After resuming ERT, they underwent frequent testing, every six months, for pulmonary function, muscle strength, exercise capacity in walking tests, and patient-reported questionnaires and daily living activities.

Researchers compared the patients’ performance on the different tests between the time they stopped ERT and after resuming ERT, as well as 36 months later.

Results showed that patients’ pulmonary function, measured by the forced vital capacity (FVC) test, and exercise capacity, assessed with the six-minute walk test (6MWT), significantly increased until the end of the 36-month follow-up. The 6MWT measures the maximum distance an individual is able to walk over six minutes on a hard, flat surface.

Patients eventually reached FVC values similar to those before they stopped ERT, but the 6MWT values remained lower than they were before therapy interruption. Self-reported fatigue of patients showed a significant decline at 36 months after resuming ERT.

Other parameters of pulmonary function (the maximum inspiratory test and the sniff nasal inspiratory pressure), walking ability (the 10-minute walk test), muscle strength, and other patient-reported outcomes showed no significant changes.

“Our data suggests that long-term interruption of ERT in LOPD [late-onset Pompe disease] may lead to deterioration of clinical meaningful parameters and quality of life. In addition, a clinical restoration after ERT cessation is possible for most of the LOPD,” the authors concluded.