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.

Abstract

BACKGROUND AND OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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.

DISCUSSION:

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.

• Authors: Lola E R Lessard, Céline Tard, Emmanuelle Salort-Campana, Sabrina Sacconi, Anthony Béhin, Guillaume Bassez, David Orlikowski, Philippe Merle, Sylvain Nollet, Laure Gallay, Frédéric Bérard, Philip Robinson, Françoise Bouhour, Pascal Laforêt
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 139 Issue 3 Pg. 107611 (07 2023) ISSN: 1096-7206 [Electronic] United States
• PMID: 37285781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• alpha-Glucosidases

Topics

• Humans
• Female
• Male
• Glycogen Storage Disease Type II (therapy)
• Retrospective Studies
• Enzyme Replacement Therapy (adverse effects)
• Hypersensitivity
• Registries
• Hypersensitivity, Immediate (chemically induced, drug therapy)
• alpha-Glucosidases (adverse effects)