Long-Term Experience with Anaphylaxis and Desensitization to Alglucosidase Alfa in Pompe Disease

Abstract

<b><i>Background and Objective:</i></b> Pompe disease (PD) is an inherited lysosomal storage disease that progresses with glycogen accumulation in many tissues, due to the deficiency of the acid-alpha glucosidase enzyme. Recombinant alglucosidase alfa (rhGAA) is the only disease-specific treatment option, in the form of enzyme replacement therapy (ERT). Anaphylaxis can develop with rhGAA. There is no study evaluating anaphylaxis and its management in PD in the long term. We aimed to evaluate the development of anaphylaxis and rapid drug desensitization (RDD) with rhGAA in children with PD. <b><i>Materials and Methods:</i></b> All children diagnosed and followed up in our institution with PD over 12 years between January 2009 and September 2021 were evaluated for development of anaphylaxis and RDD with rhGAA from medical records. <b><i>Results:</i></b> Fourteen patients, 64% of whom were female and diagnosed with PD (1 juvenile, 13 infantile types) during the study period included in the study. The median age at diagnosis was 3.2 months (1–40 months). The median follow-up time of the patients was 20 months (1–129 months). Thirteen patients were given rhGAA, one died before ERT. Four (30.8%) patients developed moderate to severe anaphylaxis, and RDD was applied with rhGAA. A total of 390 RDDs have been performed so far without any serious breakthrough reactions during all RDDs. <b><i>Conclusions:</i></b> Anaphylaxis with rhGAA is not rare and RDD with rhGAA is safe and effective in the long term.

Advances for pediatricians in 2022: allergy, anesthesiology, cardiology, dermatology, endocrinology, gastroenterology, genetics, global health, infectious diseases, metabolism, neonatology, neurology, oncology, pulmonology

“…Main objectives of the analysis, supported by useful diagrams, are identification of two types of immune reactions against ERT, quantification of risk factors for immunogenicity, choose of prophylaxis protocols in relation to cross reactive immunological material status, importance of immune-tolerance induction protocols in patients who develop antibodies during ERT, recommendations on the test to be performed before starting immunomodulation and tips on managing the frequent (up to 50%) hypersensitivity reactions during ERT. The authors conclude that further studies are needed to improve actual management protocols [123].…”

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“…The development of next-generation ERTs and gene therapies for Pompe disease is crucial in order to address the limitations of current treatments and provide more effective options for patients [1,2,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. These advancements aim to overcome challenges such as poor distribution to muscles, reduced muscle uptake, interference from antibodies, and limited penetration of the blood-brain barrier.…”

What is the Clue to Cure Pompe Disease in Childhood?

“…The development of next-generation ERTs and gene therapies for Pompe disease is crucial in order to address the limitations of current treatments and provide more effective options for patients [1,2,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. These advancements aim to overcome challenges such as poor distribution to muscles, reduced muscle uptake, interference from antibodies, and limited penetration of the blood-brain barrier.…”