Clinical outcomes among young patients with Fabry disease who initiated agalsidase beta treatment before 30 years of age: An analysis from the Fabry Registry.

BACKGROUND

Clinical manifestations of classic Fabry disease (α-galactosidase A deficiency) usually occur in childhood, while complications involving major organs typically develop in adulthood. Outcomes of Fabry-specific treatment among young patients have not been extensively reported. Our aim was to analyze clinical outcomes among patients aged 5-30 years at initiation of treatment with agalsidase beta using data from the Fabry Registry (NCT00196742, sponsor: Sanofi).

METHODS

Reported GLA variants were predicted to be associated with the classic phenotype or not classified in fabry-database.org. Linear mixed models were conducted to assess changes over ≥2-year follow-up in the estimated glomerular filtration rate (eGFR) stratified by low (LRI) and high (HRI) renal involvement (defined by proteinuria/albuminuria levels), and changes in interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) Z-scores stratified by median age at first treatment. Self-reports ('yes'/'no') of abdominal pain, diarrhea, chronic peripheral pain (denoting neuropathic pain), and acute pain crises at baseline were compared with reports after ≥0.5-year and ≥2.5-year follow-up using McNemar's test.

RESULTS

Male (n = 117) and female patients (n = 59) with LRI initiated treatment at a median age of 19.9 and 23.6 years, respectively, and were followed for a median of 6.3 and 5.0 years, respectively. The eGFR slopes were -1.18 (P

CONCLUSIONS

During sustained treatment with agalsidase beta in young Fabry patients with a predicted classic phenotype or with unclassified GLA variants with similar characteristics, the decline in eGFR was modest among male and female patients with LRI. The greater decline in eGFR among older, proteinuric (i.e., HRI) males may suggest a benefit of earlier treatment. Overall, echocardiographic variables remained stable, particularly among males and younger females. Significant reductions in symptom reports occurred primarily among males after longer follow-up and were less noticeable among females. These observed trends are suggestive of an overall improvement after treatment in young patients, but warrant larger longitudinal studies.

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest R.J.H. is a member of the Fabry Registry Advisory Board, consults with Amicus Therapeutics and Sanofi, and has been an investigator in clinical trials sponsored by Amicus Therapeutics, Idorsia Pharmaceuticals, Protalix Biotherapeutics, Sangamo Therapeutics, Sanofi, and Takeda. These activities have been monitored and found to be in compliance with the conflict-of-interest policies at Cincinnati Children's Hospital Medical Center. G.H.C. has consulting arrangements with and received speaking fees from Sanofi, and has received travel support from Sanofi and Takeda. J.L.J. has received Advisory Board honoraria from Sanofi. M.Y. is a former employee of Sanofi. E.P. is a full-time employee of Sanofi. Both may hold/have held stock and/or stock options in that company. E.B. has received Advisory Board honoraria from Amicus Therapeutics, Chiesi Pharmaceuticals, Greenovation Biotech, Sanofi, and Takeda, speaker honoraria and research grants from Amicus Therapeutics, Chiesi Pharmaceuticals, Sanofi, and Takeda, and travel support from Amicus Therapeutics. U.F.R. has received Advisory Board honoraria from Amicus Therapeutics, Freeline Therapeutics, Sanofi, and Takeda, speaker honoraria from Amicus Therapeutics, Sanofi, and Takeda, grant support from Sanofi and Takeda, and is a member of the European Advisory Board of the Fabry Registry. D.P.G. has received consulting honoraria from Idorsia Pharmaceuticals, Sanofi, and Takeda, and speaker honoraria and travel support from Amicus Therapeutics, Sanofi, and Takeda. N.G. has received travel support from Sanofi and Takeda. A.J. has received Advisory Board honoraria from Amicus Therapeutics, Sanofi, and Takeda, speaker honoraria from Amicus Therapeutics, BioMarin Pharmaceutical, and Sanofi, and travel support from Amicus Therapeutics and Sanofi. I.K. has received speaker honoraria and travel support from Sanofi and Takeda. A.K. has received research grants, reimbursement for travel, and consulting payments from Sanofi, Stealth BioTherapeutics, and Takeda, received research grants and reimbursement for travel from Protalix Biotherapeutics and Reata Pharmaceuticals, received research grants from Astellas Pharma, Cyclerion Therapeutics, Idorsia Pharmaceuticals, Mitobridge, and PTC Therapeutics, and received consulting payments from Akros Pharma, Alexion Pharmaceuticals, Astellas Pharma, Homology Medicines, Lumleian, Mitobridge, NeuroVive Pharmaceutical, Reneo Pharmaceuticals, and Zogenix. A.M.M. has received Advisory Board honoraria from BioMarin Pharmaceutical and Sanofi, and speaker honoraria and travel support from Alexion Pharmaceuticals, BioMarin Pharmaceutical, and Sanofi. C.T. is a member of the European Fabry Registry Board of Advisors, has received consultancy honoraria from Acelink Therapeutics, Amicus Therapeutics, Chiesi Pharmaceuticals, Freeline Therapeutics, and Sanofi, and is investigator in studies supported by Freeline Therapeutics, Idorsia Pharmaceuticals, Protalix Biotherapeutics, Sanofi, and Takeda. W.R.W. consults for Amicus Therapeutics, Sanofi, and Takeda, and is an investigator in clinical studies for Fabry disease sponsored by Amicus Therapeutics, Freeline Therapeutics, Idorsia Pharmaceuticals, 4D Molecular Therapeutics, Protalix Biotherapeutics, Sangamo Therapeutics, and Sanofi. These activities are monitored and are in compliance with the conflict-of-interest policies at Emory University School of Medicine. H.W.Y. has received honoraria from Sanofi. A.P.B. has received speaker honoraria and travel support from Amicus Therapeutics, Freeline Therapeutics, Sanofi, and Takeda, and is a member of the European Advisory Board of the Fabry Registry. M.M. is a member of the Fabry Registry Board, has an investigator-initiated research grant from Sanofi, performs laboratory work and is a consultant to Sanofi for clinical trial design, received speaker fees and travel support from Sanofi for non-promotional presentations (these interests have been reviewed and managed by the University of Minnesota in accordance with its conflict-of-interest policies), is a consultant and performs laboratory work for Amicus Therapeutics, and is a consultant to Acelink Therapeutics, Avrobio, Freeline Therapeutics, and Sangamo Therapeutics.