Abstract
Evaluating the relationship between infusion-related reactions and anti-drug antibody status: Results from 111 patients with Fabry disease treated with pegunigalsidase alfa
Molecular genetics and metabolism, Vol.144(2), 108768
02/2025
DOI: 10.1016/j.ymgme.2024.108768
Abstract
PEGylation of biologics can reduce immunogenicity by masking epitopes and/or decreasing antidrug antibody (ADA) binding affinity. For enzyme replacement therapies (ERTs), this may lower infusion-related reactions (IRRs) incidence. The BALANCE study in Fabry disease showed lower IRR rates among patients who switched to PEGylated ERT, pegunigalsidase alfa (PA), than patients remaining on agalsidase beta, despite similar proportions of patients experiencing IRRs. Overall, patients with ADAs had higher risk of IRRs with both ERTs. To further understand the association between IRR occurrence (during and up to 2 h post-infusion) and ADAs, we analyzed ERT-naïve and ERT-switch patients receiving PA 1 mg/kg in trials. Patients were grouped as: no IRRs, 1 IRR at first infusion (1-IRR-first), 1 IRR at later infusions (1-IRR-later), or multiple IRRs. Of 111 patients (ERT-naïve = 17; ERT-switch = 94), 85 (77 %) experienced no IRRs, while 26 (23 %; ERT-naïve = 4, ERT-switch = 22) experienced 52 IRRs with PA (rate: 0.7/100 infusions); most IRRs (85 %) occurred during the first treatment year. Eighteen (69 %) patients experienced 1 IRR (1-IRR-first = 9; 1-IRR-later = 9), whereas 8 (31 %) experienced multiple IRRs; 4 patients withdrew after first (n = 3) or second infusion (n = 1). The proportion of males (81 % vs 58 %) and baseline IgG ADA-positive patients (38 % vs 20 %) was higher in those with IRRs versus no IRRs, respectively. All 1-IRR-first patients were baseline IgG ADA-negative; 7/9 (78 %) 1-IRR-later patients were baseline IgG ADA-positive; 6/9 (67 %) had medium-high (5600–14,000) or high (>14,000) ADA titers before IRR occurrence. 20 % (17/85) of patients without IRRs were baseline IgG ADA-positive; 28/85 had at least 1 ADA-positive test, 9 of whom had medium-high or high ADA titers. As reported with other ERTs, patients with ADAs were at higher risk of IRRs; nevertheless, 20 % of patients had no IRRs while having baseline ADAs, suggesting that specific ADA characteristics may play a role, among other factors, in risk of IRRs.
Details
- Title: Subtitle
- Evaluating the relationship between infusion-related reactions and anti-drug antibody status: Results from 111 patients with Fabry disease treated with pegunigalsidase alfa
- Creators
- Robert J. Hopkin - Cincinnati Children's Hospital Medical CenterDerralynn Hughes - University College LondonJohn A. Bernat - University of IowaAleš Linhart - General University Hospital in PragueNicola Longo - University of UtahCamilla Tøndel - Haukeland University HospitalBojan Vujkovac - Splošna Bolnišnica Slovenj GradecAntonio Pisani - University of Naples Federico IIJasmine Knoll - Phoenix Children's HospitalIrene Koulinska - ChiesiGiovanni Piotti - Chiesi USA, Boston, MA, USARaul Chertkoff - Protalix BioTherapeuticsSari Alon - Protalix BioTherapeuticsAnat Sakov - DataSights, Haifa, IsraelEric L. Wallace - University of Alabama at Birmingham
- Resource Type
- Abstract
- Publication Details
- Molecular genetics and metabolism, Vol.144(2), 108768
- DOI
- 10.1016/j.ymgme.2024.108768
- ISSN
- 1096-7192
- eISSN
- 1096-7206
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 02/2025
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984780238902771
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