P.70Discontinuation of enzyme replacement therapy in adults with Pompe disease: evaluating motives and clinical course

Abstract

At Erasmus MC, a multidisciplinary expert committee decides on starting and stopping of enzyme replacement therapy (ERT) in patients with Pompe disease. In adults with Pompe disease who discontinued ERT, we evaluate motives and subsequent clinical course, aiming to add to the use and optimization of the European Pompe Consortium (EPOC) treatment guidelines. We analyzed data of patients participating in an ongoing, prospective cohort study, who discontinued ERT for any reason during the study period. We found that from 111 ERT treated patients, 24 patients discontinued ERT. In 10/24 patients discontinuation was due to medical or personal reasons. Reasons for discontinuation included: infusion associated reactions (n=4), high antibodies counteracting the effect of ERT (n=1), the patient's wish to stop (n=2), non-compliance to the treatment protocol (n=1), severe comorbidity (n=1) and deterioration of clinical condition despite ERT (n=1). In 3 patients with sufficient follow up data after treatment cessation (follow up 1.3 – 8.0 years), disease course after discontinuation was similar to estimated natural disease progression. In 14/24 patients ERT ended at decease, in 10/14 patients the cause of death was related to Pompe disease. Although all 10 patients were severely affected at start of ERT, ERT had been effective in the majority (n=8). We conclude that, although the EPOC consensus considers restart of ERT if patients deteriorate faster after discontinuation than during ERT, this more rapid decline was not observed in our study. No specific EPOC criteria advises on evaluation of the effects of ERT after the first two years of treatment, we advocate regular evaluation of efficacy (every 2-3 years) during long-term treatment, particularly in advanced disease stage. We suggest to evaluate ERT in a multidisciplinary expert team, to ensure careful consideration of all relevant aspects of the disease and its treatment.