Article Text

Download PDFPDF
Original research
Treatment switch in Fabry disease- a matter of dose?
  1. Malte Lenders1,
  2. Peter Nordbeck2,
  3. Sima Canaan-Kühl3,
  4. Lukas Kreul2,
  5. Thomas Duning4,
  6. Lora Lorenz2,
  7. Christian Pogoda5,
  8. Stefan-Martin Brand6,
  9. Christoph Wanner2,
  10. Eva Brand1
  1. 1 Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology and Interdisciplinary Fabry Center Münster (IFAZ), University Hospital Münster, Münster, Germany
  2. 2 Department of Internal Medicine I, Divisions of Cardiology and Nephrology, Comprehensive Heart Failure Center, Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital and University of Würzburg, Würzburg, Germany
  3. 3 Department of Medicine, Division of Nephrology, Charité, Universitätsmedizin Campus Mitte, Berlin, Germany
  4. 4 Department of Neurology, and Interdisciplinary Fabry Center Münster (IFAZ), University Hospital Münster, Münster, Germany
  5. 5 Department of Cardiology I – Coronary and Peripheral Vascular Disease, Heart Failure, and Interdisciplinary Fabry Center Münster (IFAZ), University Hospital Münster, Münster, Germany
  6. 6 Institute of Sports Medicine, Molecular Genetics of Cardiovascular Disease, and Interdisciplinary Fabry Center Münster (IFAZ), University Hospital Münster, Münster, Germany
  1. Correspondence to Professor Eva Brand, Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology and Interdisciplinary Fabry Center Münster (IFAZ), University Hospital Münster, Münster, Germany; Eva.Brand{at}ukmuenster.de

Abstract

Background Patients with Fabry disease (FD) on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in chronic kidney disease epidemiology collaboration-based estimated glomerular filtration rate (eGFR) and a worsened plasma lyso-Gb3 decrease. Hence, the most effective dose is still a matter of debate.

Methods In this prospective observational study, we assessed end-organ damage and clinical symptoms in 78 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, which were assigned to continue this treatment (agalsidase-beta, regular-dose group, n=17); received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n=22); or were re-switched to agalsidase-beta after receiving agalsidase-alfa for 12 months (re-switch group, n=39) with a follow-up of 88±25 months.

Results No differences for clinical events were observed for all groups. Patients within the re-switch group started with the worst eGFR values at baseline (p=0.0217). Overall, eGFR values remained stable in the regular-dose group (p=0.1052) and decreased significantly in the re-switch and switch groups (p<0.0001 and p=0.0052, respectively). However, in all groups males presented with an annual loss of eGFR by –2.9, –2.5 and −3.9 mL/min/1.73 m² (regular-dose, re-switch, switch groups, all p<0.05). In females, eGFR decreased significantly only in the re-switch group by −2.9 mL/min/1.73 m² per year (p<0.01). Lyso-Gb3 decreased in the re-switch group after a change back to agalsidase-beta (p<0.05).

Conclusions Our data suggest that a re-switch to high dosage of agalsidase results in a better biochemical response, but not in a significant renal amelioration especially in classical males.

  • genetics
  • renal medicine

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

Statistics from Altmetric.com

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

View Full Text

Footnotes

  • Contributors Research idea and study design: all authors; data acquisition: ML, SC-K, PN, LL, LK, TD, SR, CP, CW, EB; data analysis/interpretation: all authors; statistical analysis: ML; manuscript writing: ML, EB. Each author contributed important intellectual content during manuscript drafting and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. EB takes responsibility that this study has been reported honestly, accurately and transparently; that no important aspects of the study have been omitted and that any discrepancies from the study as planned have been explained.

  • Funding This study was funded by Genzyme Europe. The researchers were independent of the funding agency. Grants were used for research meetings and support in collection of the data.

  • Competing interests ML and TD received speaker honoraria from Amicus Theraputics, Sanofi Genzyme and Shire/Takeda. S-MB has received speaker honoraria from Shire/Takeda. CW, SC-K and EB received speaker and advisory board honoraria from Amicus Therapeutics, Greenovation, Sanofi Genzyme and Shire/Takeda. PN received speaker and advisory board honoraria from Amicus Therapeutics, Greenovation, Idorsia, Sanofi Genzyme and Shire/Takeda. CW is a member of the Fabry Registry European Board of Advisors and received travel assistance and speaker honoraria. Research grants were given to the institutions (Würzburg and Münster) by Amicus Therapeutics, Sanofi Genzyme and Shire/Takeda.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.