Safety of Home-Based Infusion of Alglucosidase Alfa in Adults With Late-Onset Pompe Disease

ABSTRACT

Background: Biweekly infusions with alglucosidase alfa (recombinant human alpha-glucosidase), are the cornerstone of treatment in late onset Pompe disease. Home infusion therapy may improve quality of life. In many countries providing enzyme replacement therapy (ERT) at home is not possible due to safety concerns related to the risk of infusion associated reactions (IARs) or logistical constraints. The COVID-19 pandemic has prompted the need to provide ERT for Pompe patients at home. In the Netherlands, currently over 80% of infusions are given at home. Here we present data on the safety of homebased infusions in adult patients with late-onset Pompe disease (LOPD). Methods: Data on patient descriptives, infusion characteristics and IARs from patients starting ERT between 1999 and 2018 were collected and analyzed. The Dutch infusion schedule for adult lateonset patients differs from the schedule recommended by the pharmaceutical company and is as follows 0.2, 0.8, 3.5, 10 mg/kg/hour with steps of 30 minutes for the first three steps and 10 mg/kg/ hour for the remainder of the infusion. IARs were graded by the healthcare provider. If no classification was available infusions were retrospectively classified using the Common Terminology Criteria for Adverse Events (CTCAE) classification. Descriptive analyses were performed tabulating patient and infusion characteristics as well as types of IARs and actions needed to resolve these. Results: Data on 18380 infusions with alglucosidase alfa in 121 adult LOPD patients were analysed. 4961 infusions (27.0 %) were given in hospital and 13419 (73.0 %) at home. The majority of infusions (88.4%) was administered using a standard infusion schedule. In 144 (2.9%) of hospital infusions and 113 (0.8%) of home infusions an IAR occurred. Mild IARs occurred in 115 hospital infusions and in 104 infusions at home. Twenty-five moderate IARs were reported in hospital and 8 at home. Very few severe IARs occurred (4 in hospital, 1 at home). The most prevalent symptoms in hospital were itching and chills;at home chills and trembling were most prevalent. The most common most severe interventions taken in hospital in response to an IAR were giving medication (antihistamines), or pausing the infusion and restarting it later. This was also the most common intervention at home. Sixteen infu-sions (11.1%) in hospital and 6 infusions (5.3%) at home were stopped completely after the IAR occurred. Only one IAR in the home situation required immediate clinical evaluation in hospital. The consecutive infusion after an IAR occurred in hospital, patients most commonly received premedication or the infusion scheme was adapted, whereas at home after the majority of IARs no action was taken. The most common premedication in hospital were an antihistamine and a corticosteroid and at home an antipyretic and antihistamine were most common. Conclusion: Our data demonstrate that very few IARs occur during alglucosidase alfa infusions in adult patients with LOPD. Very few severe IARs occurred. The majority of IARs at home were mild and did not require additional medical intervention. This demonstrates that alglucosidase alfa can be safely administered in the home situation, provided the appropriate infrastructure is present.