Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease

Harmke A van Kooten; Imke A M Ditters; Marianne Hoogeveen-Westerveld; Edwin H Jacobs; Johanna M P van den Hout; Pieter A van Doorn; W W M Pim Pijnappel; Ans T van der Ploeg; Nadine A M E van der Beek

doi:10.1186/s13023-022-02175-2

Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease

Orphanet J Rare Dis. 2022 Feb 2;17(1):31. doi: 10.1186/s13023-022-02175-2.

Authors

Harmke A van Kooten¹, Imke A M Ditters², Marianne Hoogeveen-Westerveld³, Edwin H Jacobs³, Johanna M P van den Hout², Pieter A van Doorn¹, W W M Pim Pijnappel³, Ans T van der Ploeg², Nadine A M E van der Beek^{4

5}

Affiliations

¹ Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
² Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC - Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
³ Department of Pediatrics, Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
⁴ Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. n.beek@erasmusmc.nl.
⁵ Department of Neurology, Erasmus University Medical Center, Mailbox 2040, 3000 CA, Rotterdam, the Netherlands. n.beek@erasmusmc.nl.

Abstract

Background: Enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA, alglucosidase alfa) has improved survival, motor outcomes, daily life activity and quality of life in Pompe patients. However, ERT in Pompe disease often induces formation of antibodies, which may reduce the efficacy of treatment and can lead to adverse events. In this study antibody formation and their effect on clinical outcome in patients with childhood onset Pompe disease treated with enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) are analyzed.

Methods: Enzyme-linked immunosorbent assay (ELISA) was used to determine anti-rhGAA antibody titers at predefined time points. The effect of antibodies on rhGAA activity (neutralizing effects) was measured in vitro. Clinical effects were evaluated by assessing muscle strength (MRC score) and function (QMFT-score), pulmonary function and infusion associated reactions (IARs).

Results: Twenty-two patients were included (age at start ERT 1.1-16.4 years, median treatment duration 12.4 years). Peak antibody titers were low (< 1:1250) in 9%, intermediate (1:1250-1:31,250) in 68% and high (≥ 1:31250) in 23% of patients; three patients (14%) had more than one titer of ≥ 1:31,250. Four patients (18%) experienced IARs; two patients from the high titer group had 86% of all IARs. Inhibition of intracellular GAA activity (58%) in vitro was found in one sample. The clinical course did not appear to be influenced by antibody titers.

Conclusions: Ninety-one percent of childhood onset Pompe patients developed anti-rhGAA antibodies (above background level), a minority of whom had high antibody titers at repeated time points, which do not seem to interfere with clinical outcome. High antibody titers may be associated with the occurrence of IARs. Although the majority of patients does not develop high titers; antibody titers should be determined in case of clinical deterioration.

Keywords: Antibodies; Enzyme replacement therapy; Pompe disease; Recombinant human alpha-glucosidase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies / therapeutic use
Enzyme Replacement Therapy / adverse effects
Glycogen Storage Disease Type II* / drug therapy
Humans
Quality of Life
alpha-Glucosidases / therapeutic use

Substances

Antibodies
alpha-Glucosidases