Hypersensitivity infusion-associated reactions induced by enzyme replacement therapy in a cohort of patients with late-onset Pompe disease: An experience from the French Pompe Registry

• Published in: Molecular genetics and metabolism Vol. 139; no. 3; p. 107611
• Main Authors: Lessard, Lola E.R., Tard, Céline, Salort-Campana, Emmanuelle, Sacconi, Sabrina, Béhin, Anthony, Bassez, Guillaume, Orlikowski, David, Merle, Philippe, Nollet, Sylvain, Gallay, Laure, Bérard, Frédéric, Robinson, Philip, Bouhour, Françoise, Laforêt, Pascal
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2023; Elsevier
• Subjects: Desensitization; Drug allergy; Drug hypersensitivity reaction; Enzyme-replacement therapy; Infusion-associated reaction; Late-onset Pompe disease; Life Sciences; CRP; N/A; FDA; PT; ERT; F; NSAID; DP; AntiHis; M; Late-onset Pompe disease; Drug allergy; DHR; Premed; SD; Drug hypersensitivity reaction; Infusion-associated reaction; LOPD; IDR; HBP; Desensitization; MR; GAA; SWORD; Enzyme-replacement therapy; IQR; ICU/EU; IV; ATB; CS; mAbs; IAR; NM
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2023.107611

Pompe disease is a rare hereditary glycogen storage disorder due to lysosomal acid alpha-glucosidase deficiency. Enzyme replacement therapy (ERT) is the only available treatment. Infusion-associated reactions (IAR) are challenging since there are no guidelines for ERT rechallenge after a drug hypersensitivity reaction (DHR) in Pompe disease. The objective of the present study was to describe IAR and their management in late-onset Pompe disease (LOPD) patients in France, and to discuss the various possibilities of ERT rechallenge. An exhaustive screening of LOPD patients receiving ERT between 2006 and 2020 from the 31-participating hospital-based or reference centers was performed. The patients who had presented at least one hypersensitivity IAR (=DHR) episode were included. Demographic characteristics of the patients, IAR onset and timing, were retrospectively collected from the French Pompe Registry. Fifteen patients among 115 treated LOPD patients in France presented at least 1 IAR; 80.0% were women. Twenty-nine IAR were reported; 18 (62.1%) IAR were Grade I reactions, 10 (34.5%) IAR were Grade II, and 1 (3.4%) IAR was Grade III. IgE-mediated hypersensitivity was found in 2/15 patients (13.3%). The median [IQR] time from ERT introduction to the first IAR was 15.0 months [11.0–24.0]. ERT was safely and effectively re-introduced either with premedication alone, or in combination with either modified regimen or desensitization protocol, in all 9 rechallenged patients; including in patients with IgE-mediated hypersensitivity, in the patient with the Grade III reaction, as well as in patients with very high anti-GAA titer. Based on the results herein and previous reports, we discuss premedication and modified regimen for Grade I reactions, and desensitization in Grade II and III reactions. In conclusion, ERT-induced IAR can be safely and effectively managed with a modified regimen or desensitization protocol in LOPD patients. •Most hypersensitivity reactions were Grade I and due to non-IgE hypersensitivity.•Most hypersensitivity reactions occurred in female LOPD patients.•Hypersensitivity reactions may occur after one year of well-tolerated ERT.•Modified regimen and desensitization were safe and effective to reintroduce ERT.