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.
| Original language | English |
|---|---|
| Article number | 31 |
| Journal | Orphanet Journal of Rare Diseases |
| Volume | 17 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2 Feb 2022 |
Bibliographical note
Funding Information:Several of the authors of this publication are members of the European Reference Networks for Hereditary Metabolic Disorders (Metab-ERN) and Rare Neuromuscular Diseases (EURO-NMD) and/or of the Netherlands Neuromuscular Center (NL-NMD).
Funding Information:
This study was funded by ZonMw—the Netherlands Organization for Health Research and Development [Grant No. 09150161910230 (Veni to NvdB)];Sophia Children’s Hospital Foundation (SSWO) [Project No. S17-32]; Metakids [Project No. 2016-063]; Ministry of Economic Affairs under TKI-Allowance under the TKI-program Life Sciences & Health [Project No. LSHM16008]. This study was also supported in part by Sanofi-Genzyme. Sanofi-Genzyme did not have any influence on the content or design of the study and the drafting and content of the manuscript nor did Sanofi-Genzyme cover the costs of the study drug. NvdB received a post-doctoral fellowship from the Prinses Beatrix Spierfonds (W.F16-03). The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.
Publisher Copyright:
© 2022, The Author(s).
