{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:40:28Z","timestamp":1789123228010,"version":"build-2803163510"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/501100004243","name":"Prinses Beatrix Spierfonds","doi-asserted-by":"publisher","award":["W.OR16-07"],"award-info":[{"award-number":["W.OR16-07"]}],"id":[{"id":"10.13039\/501100004243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004243","name":"Prinses Beatrix Spierfonds","doi-asserted-by":"publisher","award":["W.TR 19-0"],"award-info":[{"award-number":["W.TR 19-0"]}],"id":[{"id":"10.13039\/501100004243","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Holland TKI subsidy","award":["EMCLSHPC24044"],"award-info":[{"award-number":["EMCLSHPC24044"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BioDrugs"],"DOI":"10.1007\/s40259-026-00802-z","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T09:55:10Z","timestamp":1789120510000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Anti-drug Antibodies on the Bioavailability of Alglucosidase Alfa in Classic Infantile Pompe Disease"],"prefix":"10.1007","author":[{"given":"Martha Caterina","family":"Faraguna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00ebl A. M.","family":"Lambregts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Barzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin H.","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Hoogeveen-Westerveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine A. M. E.","family":"van der Beek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. W. M. Pim","family":"Pijnappel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Gasperini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Preijers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8091-263X","authenticated-orcid":false,"given":"Johanna M. P.","family":"van den Hout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ans T.","family":"van der Ploeg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"802_CR1","doi-asserted-by":"publisher","unstructured":"van der Ploeg AT, Reuser AJJ. Pompe\u2019s disease. Lancet. 2008. https:\/\/doi.org\/10.1016\/s0140-6736(08)61555-x.","DOI":"10.1016\/s0140-6736(08)61555-x"},{"key":"802_CR2","doi-asserted-by":"publisher","unstructured":"Poelman E, van den Dorpel JJA, Hoogeveen-Westerveld M, van den Hout JMP, van der Giessen LJ, van der Beek NAME, et al. Effects of higher and more frequent dosing of alglucosidase alfa and immunomodulation on long-term clinical outcome of classic infantile Pompe patients. J Inherit Metab Dis. 2020. https:\/\/doi.org\/10.1002\/jimd.12268.","DOI":"10.1002\/jimd.12268"},{"key":"802_CR3","doi-asserted-by":"publisher","unstructured":"van Gelder CM, Poelman E, Plug I, Hoogeveen-Westerveld M, van der Beek NAME, Reuser AJJ, et al. Effects of a higher dose of alglucosidase alfa on ventilator-free survival and motor outcome in classic infantile Pompe disease: an open-label single-center study. J Inherit Metab Dis. 2016. https:\/\/doi.org\/10.1007\/s10545-015-9912-y.","DOI":"10.1007\/s10545-015-9912-y"},{"key":"802_CR4","doi-asserted-by":"publisher","unstructured":"Spada M, Pagliardini V, Ricci F, Biamino E, Mongini T, Porta F. Early higher dosage of alglucosidase alpha in classic Pompe disease. J Pediatr Endocrinol Metab. 2018. https:\/\/doi.org\/10.1515\/jpem-2018-0336.","DOI":"10.1515\/jpem-2018-0336"},{"key":"802_CR5","doi-asserted-by":"publisher","unstructured":"Ditters IAM, Huidekoper HH, Kruijshaar ME, Rizopoulos D, Hahn A, Mongini TE, et al. Effect of alglucosidase alfa dosage on survival and walking ability in patients with classic infantile Pompe disease: a multicentre observational cohort study from the European Pompe Consortium. Lancet Child Adolesc Health. 2022. https:\/\/doi.org\/10.1016\/s2352-4642(21)00308-4.","DOI":"10.1016\/s2352-4642(21)00308-4"},{"key":"802_CR6","doi-asserted-by":"publisher","unstructured":"Kishnani PS, Kronn D, Suwazono S, Broomfield A, Llerena J, Al-Hassnan ZN, et al. Higher dose alglucosidase alfa is associated with improved overall survival in infantile-onset Pompe disease (IOPD): data from the Pompe registry. Orphanet J Rare Dis. 2023. https:\/\/doi.org\/10.1186\/s13023-023-02981-2.","DOI":"10.1186\/s13023-023-02981-2"},{"key":"802_CR7","doi-asserted-by":"publisher","unstructured":"Chien YH, van der Ploeg A, Jones S, Byrne B, Vellodi A, Leslie N, et al. Survival and developmental milestones among Pompe registry patients with classic infantile-onset Pompe disease with different timing of initiation of treatment with enzyme replacement therapy. J Neuromuscul Dis. 2015. https:\/\/doi.org\/10.3233\/JND-159053.","DOI":"10.3233\/JND-159053"},{"key":"802_CR8","doi-asserted-by":"publisher","unstructured":"van Gelder CM, Hoogeveen-Westerveld M, Kroos MA, Plug I, van der Ploeg AT, Reuser AJJ. Enzyme therapy and immune response in relation to CRIM status: the Dutch experience in classic infantile Pompe disease. J Inherit Metab Dis. 2015. https:\/\/doi.org\/10.1007\/s10545-014-9707-6.","DOI":"10.1007\/s10545-014-9707-6"},{"key":"802_CR9","doi-asserted-by":"publisher","unstructured":"Banugaria SG, Patel TT, Kishnani PS. Immune modulation in Pompe disease treated with enzyme replacement therapy. Expert Rev Clin Immunol. 2012. https:\/\/doi.org\/10.1586\/eci.12.40.","DOI":"10.1586\/eci.12.40"},{"key":"802_CR10","doi-asserted-by":"publisher","unstructured":"Desai AK, Li C, Rosenberg AS, Kishnani PS. Immunological challenges and approaches to immunomodulation in Pompe disease: a literature review. Ann Transl Med. 2019. https:\/\/doi.org\/10.21037\/atm.2019.05.27.","DOI":"10.21037\/atm.2019.05.27"},{"key":"802_CR11","doi-asserted-by":"publisher","unstructured":"Desai AK, Shrivastava G, Grant CL, Wang RY, Burt TD, Kishnani PS. An updated management approach of Pompe disease patients with high-sustained anti-rhGAA IgG antibody titers: experience with bortezomib-based immunomodulation. Front Immunol. 2024. https:\/\/doi.org\/10.3389\/fimmu.2024.1360369.","DOI":"10.3389\/fimmu.2024.1360369"},{"key":"802_CR12","doi-asserted-by":"publisher","unstructured":"Desai AK, Kazi ZB, Bali DS, Kishnani PS. Characterization of immune response in Cross-Reactive Immunological Material (CRIM)-positive infantile Pompe disease patients treated with enzyme replacement therapy. Mol Genet Metab Rep. 2019. https:\/\/doi.org\/10.1016\/j.ymgmr.2019.100475.","DOI":"10.1016\/j.ymgmr.2019.100475"},{"key":"802_CR13","doi-asserted-by":"publisher","unstructured":"Banugaria SG, Prater SN, Ng YK, Kobori JA, Finkel RS, Ladda RL, et al. The impact of antibodies on clinical outcomes in diseases treated with therapeutic protein: lessons learned from infantile Pompe disease. Genet Med. 2011. https:\/\/doi.org\/10.1097\/GIM.0b013e3182174703.","DOI":"10.1097\/GIM.0b013e3182174703"},{"key":"802_CR14","doi-asserted-by":"publisher","unstructured":"Faraguna MC, Crescitelli V, Bonanomi S, Kullmann GA, Boffi ML, Pretese R, et al. A comprehensive study on the effect of alglucosidase alpha and immunomodulation on survival, motor and cardiac outcome, creatine kinase and antibody titers in classic infantile Pompe disease: the Monza experience. Curr Opin Immunol. 2026. https:\/\/doi.org\/10.1016\/j.coi.2026.102725.","DOI":"10.1016\/j.coi.2026.102725"},{"key":"802_CR15","doi-asserted-by":"publisher","unstructured":"de Vries JM, van der Beek NAME, Kroos MA, \u00d6zkan L, van Doorn PA, Richards SM, et al. High antibody titer in an adult with Pompe disease affects treatment with alglucosidase alfa. Mol Genet Metab. 2010. https:\/\/doi.org\/10.1016\/j.ymgme.2010.08.009.","DOI":"10.1016\/j.ymgme.2010.08.009"},{"key":"802_CR16","doi-asserted-by":"publisher","unstructured":"Chen HA, Hsu RH, Fang CY, Desai AK, Lee NC, Hwu WL, et al. Optimizing treatment outcomes: immune tolerance induction in Pompe disease patients undergoing enzyme replacement therapy. Front Immunol. 2024. https:\/\/doi.org\/10.3389\/fimmu.2024.1336599.","DOI":"10.3389\/fimmu.2024.1336599"},{"key":"802_CR17","doi-asserted-by":"publisher","unstructured":"Poelman E, Hoogeveen-Westerveld M, Kroos-de Haan MA, van den Hout JMP, Bronsema KJ, van de Merbel NC, et al. High sustained antibody titers in patients with classic infantile Pompe disease following immunomodulation at start of enzyme replacement therapy. J Pediatr. 2018. https:\/\/doi.org\/10.1016\/j.jpeds.2017.11.046.","DOI":"10.1016\/j.jpeds.2017.11.046"},{"key":"802_CR18","doi-asserted-by":"publisher","unstructured":"Poelman E, Hoogeveen-Westerveld M, Van Den Hout JMP, Bredius RGM, Lankester AC, Driessen GJA, et al. Effects of immunomodulation in classic infantile Pompe patients with high antibody titers. Orphanet J Rare Dis. 2019. https:\/\/doi.org\/10.1186\/s13023-019-1039-z.","DOI":"10.1186\/s13023-019-1039-z"},{"key":"802_CR19","doi-asserted-by":"publisher","unstructured":"De Groot AS, Kazi ZB, Martin RF, Terry FE, Desai AK, Martin WD, et al. HLA- and genotype-based risk assessment model to identify infantile onset Pompe disease patients at high-risk of developing significant anti-drug antibodies (ADA). Clin Immunol. 2019. https:\/\/doi.org\/10.1016\/j.clim.2019.01.009.","DOI":"10.1016\/j.clim.2019.01.009"},{"key":"802_CR20","doi-asserted-by":"publisher","unstructured":"Elder ME, Nayak S, Collins SW, Lawson LA, Kelley JS, Herzog RW, et al. B-cell depletion and immunomodulation before initiation of enzyme replacement therapy blocks the immune response to acid alpha-glucosidase in infantile-onset Pompe disease. J Pediatr. 2013. https:\/\/doi.org\/10.1016\/j.jpeds.2013.03.002.","DOI":"10.1016\/j.jpeds.2013.03.002"},{"key":"802_CR21","doi-asserted-by":"publisher","unstructured":"de Faria DOS, t Groen S, Hoogeveen-Westerveld M, Nino MY, van der Ploeg AT, Bergsma AJ, et al. Update of the Pompe variant database for the prediction of clinical phenotypes: novel disease-associated variants, common sequence variants, and results from newborn screening. Hum Mutat. 2021. https:\/\/doi.org\/10.1002\/humu.24148.","DOI":"10.1002\/humu.24148"},{"key":"802_CR22","doi-asserted-by":"publisher","unstructured":"Nino MY, In \u2018t Groen SLM, Bergsma AJ, van der Beek N, Kroos M, Hoogeveen-Westerveld M, van der Ploeg AT, Pijnappel W. Extension of the Pompe mutation database by linking disease-associated variants to clinical severity. Hum Mutat. 2019;40(11):1954\u201367. https:\/\/doi.org\/10.1002\/humu.23854.","DOI":"10.1002\/humu.23854"},{"key":"802_CR23","doi-asserted-by":"publisher","unstructured":"Desai AK, Rosenberg AS, Kishnani PS. The potential impact of timing of IVIG administration on the efficacy of rituximab for immune tolerance induction for patients with Pompe disease. Clin Immunol. 2020. https:\/\/doi.org\/10.1016\/j.clim.2020.108541.","DOI":"10.1016\/j.clim.2020.108541"},{"key":"802_CR24","doi-asserted-by":"publisher","unstructured":"Ditters IAM, van der Beek N, Brusse E, van der Ploeg AT, van den Hout JMP, Huidekoper HH. Home-based enzyme replacement therapy in children and adults with Pompe disease; a prospective study. Orphanet J Rare Dis. 2023. https:\/\/doi.org\/10.1186\/s13023-023-02715-4.","DOI":"10.1186\/s13023-023-02715-4"},{"key":"802_CR25","doi-asserted-by":"publisher","unstructured":"de Vries JM, Kuperus E, Hoogeveen-Westerveld M, Kroos MA, Wens SC, Stok M, et al. Pompe disease in adulthood: effects of antibody formation on enzyme replacement therapy. Genet Med. 2017. https:\/\/doi.org\/10.1038\/gim.2016.70.","DOI":"10.1038\/gim.2016.70"},{"key":"802_CR26","doi-asserted-by":"publisher","unstructured":"Theunissen MTM, Ditters IAM, van Kooten HA, van Doorn PA, van den Hout JMP, Hoogeveen-Westerveld M, et al. Antibody formation and efficacy of enzyme replacement therapy in adults with Pompe disease: unlocking long-term insights. Genet Med. 2026. https:\/\/doi.org\/10.1016\/j.gim.2026.102578.","DOI":"10.1016\/j.gim.2026.102578"},{"key":"802_CR27","doi-asserted-by":"publisher","unstructured":"Denney WS, Duvvuri S, Buckeridge C. Simple, automatic noncompartmental analysis: the PKNCA R package. J Pharmacokinet Pharmacodyn. 2015;42:S65. https:\/\/doi.org\/10.1007\/s10928-015-9432-2.","DOI":"10.1007\/s10928-015-9432-2"},{"key":"802_CR28","doi-asserted-by":"publisher","unstructured":"Wang J, Lozier J, Johnson G, Kirshner S, Verthelyi D, Pariser A, et al. Neutralizing antibodies to therapeutic enzymes: considerations for testing, prevention and treatment. Nat Biotechnol. 2008. https:\/\/doi.org\/10.1038\/nbt.1484.","DOI":"10.1038\/nbt.1484"},{"key":"802_CR29","doi-asserted-by":"publisher","unstructured":"Desai AK, Walters CK, Cope HL, Kazi ZB, DeArmey SM, Kishnani PS. Enzyme replacement therapy with alglucosidase alfa in Pompe disease: clinical experience with rate escalation. Mol Genet Metab. 2018. https:\/\/doi.org\/10.1016\/j.ymgme.2017.12.435.","DOI":"10.1016\/j.ymgme.2017.12.435"},{"key":"802_CR30","unstructured":"European Medicines Agency. Myozyme 10 mg\/ml powder for concentrate for solution for infusion (alglucosidase alfa): Summary of Product Characteristics. Amsterdam: European Medicines Agency. 2024. https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/myozyme."},{"key":"802_CR31","doi-asserted-by":"publisher","unstructured":"Winkel LPF, Van Den Hout JMP, Kamphoven JHJ, Disseldorp JAM, Remmerswaal M, Arts WFM, et al. Enzyme replacement therapy in late-onset Pompe\u2019s disease: a three-year follow-up. Ann Neurol. 2004. https:\/\/doi.org\/10.1002\/ana.20019.","DOI":"10.1002\/ana.20019"},{"key":"802_CR32","doi-asserted-by":"publisher","unstructured":"Bronsema KJ, Bischoff R, Pijnappel WWMP, Van Der Ploeg AT, Van De Merbel NC. Absolute quantification of the total and antidrug antibody-bound concentrations of recombinant human \u03b1-glucosidase in human plasma using protein g extraction and LC-MS\/MS. Anal Chem. 2015. https:\/\/doi.org\/10.1021\/acs.analchem.5b00169.","DOI":"10.1021\/acs.analchem.5b00169"}],"container-title":["BioDrugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40259-026-00802-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40259-026-00802-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40259-026-00802-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T09:55:12Z","timestamp":1789120512000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40259-026-00802-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":32,"alternative-id":["802"],"URL":"https:\/\/doi.org\/10.1007\/s40259-026-00802-z","relation":{},"ISSN":["1173-8804","1179-190X"],"issn-type":[{"value":"1173-8804","type":"print"},{"value":"1179-190X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"assertion":[{"value":"26 July 2026","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2026","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A.T. v.d.P., J.M.P. v.d.H. and N.A.M.E v.d.B received funding for research, clinical trials, and\/or as advisor from various industries working on ERT and next-generation therapies in the field of Pompe disease under agreements with Erasmus MC University Medical Center. W.W.M.P. is co-founder and unpaid Chief Scientific Officer of LentiCure, a company developing gene therapy for lysosomal disorders including Pompe disease. E.H.J. and M.H.W. received funding for clinical trial and contract work from Spark Therapeutics and Amicus Therapeutics. M.C.F, T.P., I.B., D.L., and S.G. declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of Interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Patients with Pompe disease followed at the Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center in Rotterdam, the Netherlands are enrolled in the prospective protocol MEC-2007-103, approved by the Medical Ethical Committee of Erasmus Medical Center.","order":2,"name":"Ethics","label":"Ethical Approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All original data are present in the manuscript. Further enquiries can be addressed to the corresponding author.","order":3,"name":"Ethics","label":"Data Availability Statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Patients and\/or their parents or legal guardians provide written consent to participate in the study.","order":4,"name":"Ethics","label":"Patient Consent Statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"M.C.F participated in planning the project and design of experiments, collected data, analyzed and interpreted data and wrote the draft of the manuscript. A.T.P. and J.M.P.H. conceived the project, designed experiments, interpreted data, participated in discussions and edited several versions of this manuscript. I.B. and T.P. contributed to PK analysis, results interpretation, improvement of figure quality and reviewed several versions of the paper. D.L., S.G., W.W.M.P. and N.A.M.E. v.d.B. participated in data interpretation and reviewed several drafts of the manuscript. E.H.J and M.H.W. supervised enzyme activity measurement and ELISA assay, analyzed and interpreted data and contributed to the manuscript preparation.","order":5,"name":"Ethics","label":"Author Contributions","group":{"name":"EthicsHeading","label":"Declarations"}}]}}