Improvement of Fabry Disease-Related Gastrointestinal Symptoms in a Significant Proportion of Female Patients Treated with Agalsidase Beta: Data from the Fabry Registry

Abstract

Fabry disease, an X-linked inherited lysosomal storage disorder, is caused by mutations in the gene encoding α-galactosidase, GLA. In patients with Fabry disease, glycosphingolipids accumulate in various cell types, triggering a range of cellular and tissue responses that result in a wide spectrum of organ involvement. Although variable, gastrointestinal symptoms are among the most common and significant early clinical manifestations; they tend to persist into adulthood if left untreated. To further understand the effects of sustained enzyme replacement therapy (ERT) with agalsidase beta on gastrointestinal symptoms in heterozygotes, a data analysis of female patients enrolled in the Fabry Registry was conducted. To be included, females of any age must have received agalsidase beta (average dose 1.0 mg/kg every 2 weeks) for at least 2.5 years. Measured outcomes were self-reported gastrointestinal symptoms (abdominal pain, diarrhea). Outcomes at baseline and last follow-up, and their change from baseline to last follow-up, were assessed. Relevant data were available for 168 female patients. Mean age at the start of ERT was 43 years and mean treatment duration 5.7 years. Baseline pre-treatment abdominal pain was reported by 45% of females and diarrhea by 39%. At last follow-up, 31% reported abdominal pain (p < 0.01) and 27% diarrhea (p < 0.01). The results of this Fabry Registry analysis suggest that while on sustained treatment with agalsidase beta (1.0 mg/kg every 2 weeks), both abdominal pain and diarrhea improved in many female patients with Fabry disease.

Synopsis

Enzyme replacement therapy with agalsidase beta alleviates both abdominal pain and diarrhea in a significant proportion of female patients with Fabry disease.

Compliance with Ethics Guidelines

Conflict of Interest

See the financial activities section below.

This research was funded by Sanofi Genzyme, the sponsor of the Fabry Registry.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committees on human experimentation (institutional and national) and with the Helsinki Declaration of 1975 (revised in 2000). Each independent Fabry Registry site is responsible for obtaining a patient’s informed written consent to submit their health information to the Registry, and to use and disclose this information in subsequent aggregate analyses.

Author Contributions

William R. Wilcox, Ulla Feldt-Rasmussen, Alberto Ortiz, Dominique P. Germain, Frank Weidemann, and Robert J. Hopkin contributed to the concept/design of the manuscript, data acquisition, data analysis/interpretation, drafting the manuscript, and critically revising it.

Ana Maria Martins, Ana Jovanovic, Carmen Varas, and Katherine Nicholls contributed to the data acquisition, data analysis/interpretation, drafting the manuscript, and critically revising it.

Roberta M. Lemay contributed to the concept/design of the manuscript, data analysis/interpretation, drafting the manuscript, and critically revising it.

Financial Relationships for the Work Under Consideration for Publication

The authors received medical writing/editing support in the preparation of this manuscript from Alessia Piazza and Tom Rouwette of Excerpta Medica, funded by Sanofi Genzyme. The authors also thank Hans Ebels for providing medical writing/editing services and Badari Gudivada for providing programming support on behalf of Sanofi Genzyme. A. Ortiz was supported by ISCIII intensificación de la actividad investigadora. This research was funded by Sanofi Genzyme, the sponsor of the Fabry Registry.

Relevant Financial Activities Outside the Submitted Work

• William R. Wilcox consults for Sanofi Genzyme and is an investigator in clinical studies and trials sponsored by Sanofi Genzyme, Shire HGT, Amicus Therapeutics, and Protalix Corporation. These activities are monitored and are in compliance with the conflict of interest policies at Emory University School of Medicine.

• Ulla Feldt-Rasmussen has received honoraria for lectures and participation in advisory boards from Sanofi Genzyme, Shire HGT, and Amicus Therapeutics, and has received research funds from Sanofi Genzyme and Shire HGT.

• Ana Maria Martins is a member of the Fabry Registry Board of Advisors and has received research funds, travel support, and speaking fees from Sanofi Genzyme.

• Alberto Ortiz is a consultant for Sanofi Genzyme and has received speaker fees from Shire HGT.

• Roberta M. Lemay is an employee of Sanofi Genzyme.

• Ana Jovanovic is a member of the Fabry Registry Board of Advisors and has received advisory board fees and honoraria for lectures from Sanofi Genzyme, Shire HGT, and Amicus Therapeutics.

• Dominique P. Germain is a consultant for Sanofi Genzyme and Shire HGT and has received honoraria for lectures from Sanofi Genzyme, Shire HGT, and Amicus Therapeutics.

• Carmen Varas is a member of the Fabry Registry Board of Advisors.

• Katherine Nicholls has received research support and travel grants from Sanofi Genzyme, Amicus Therapeutics, and Shire HGT, and speaker honoraria from Sanofi Genzyme and Shire HGT.

• Frank Weidemann has received speaker honoraria from Sanofi Genzyme and Shire HGT, is a member of the Fabry Registry European Board of Advisors, and has received travel assistance and speaker honoraria. Research grants were given to his institution by Sanofi Genzyme and Shire HGT.

• Robert J. Hopkin consults with Sanofi Genzyme and Shire HGT and has been an investigator in clinical trials sponsored by Sanofi Genzyme, Shire HGT, and Amicus Therapeutics. These activities have been monitored and found to be in compliance with the conflict of interest policies at Cincinnati Children’s Hospital Medical Center.