Background: Pompe disease is a rare metabolic myopathy. In adult patients, progressive weakness of limb-girdle and respiratory muscles often leads to wheelchair and respirator dependency. Clinical studies have shown enzyme replacement therapy (ERT) to positively affect motor and respiratory outcomes. Here we investigate whether ERT reduces patients' risk of needing a wheelchair or respirator. Methods: Data were collected as part of a prospective international survey, the IPA/Erasmus MC Pompe survey, which was conducted annually between 2002 and 2016. We excluded patients who were already using a wheelchair or respirator, those under 18 at survey entry, and those who had missing information. Time-dependent Cox proportional hazard models were used. Results: The inclusion criteria for analyzing the risk of wheelchair use were met by 189 patients (median age 47 years; range 18-75). During follow-up, 126 (67%) started ERT. Over 1120 person-years of follow-up (median 5 years), 46 became wheelchair dependent, 16 of whom used ERT. After adjustment for disease duration, sex and country, ERT reduced the risk for wheelchair use (HR 0.36; 95% CI 0.17-0.75). For analyses of respirator use, 177 patients met the inclusion criteria (median age 46 years; range 18-73). Over 1190 person-years of follow-up (median 6 years), 125 patients (71%) were treated and 48 started respiratory support, 28 of whom received ERT. We found no association between ERT and the risk for respirator use (HR 1.23; 95% CI 0.61-2.47). Conclusions: Our study found that ERT reduced the risk for wheelchair dependency. We could not demonstrate an effect on respiratory support.

Enzyme replacement therapy, ERT, Hazard ratio, Pompe disease, Respiratory support, Wheelchair,
Orphanet journal of rare diseases
Department of Clinical Genetics

van der Meijden, J.C, Kruijshaar, M.E, Rizopoulos, D, van Doorn, P.A, van der Beek, N.A.M.E, & van der Ploeg, A.T. (2018). Enzyme replacement therapy reduces the risk for wheelchair dependency in adult Pompe patients. Orphanet journal of rare diseases, 13(1). doi:10.1186/s13023-018-0824-4