Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme.

Abstract

PURPOSE:

To determine if enzyme replacement therapy, involving intravenous infusions of recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme), could be safely continued in patients with Fabry disease who had been withdrawn from a previous clinical trial as a precautionary, protocol-specified measure due to detection of serum IgE antibodies or skin-test reactivity to agalsidase beta.

METHODS:

The rechallenge infusion protocol specified strict patient monitoring conditions and graded dosing and infusion-rate schemes that were adjusted according to each patient's tolerance to the infusion. Six males (age: 26-66 years) were enrolled.

RESULTS:

During rechallenge, five patients received between 4 and 27 infusions; one patient voluntarily withdrew after one infusion because of recurrence of infusion-associated reactions. No anaphylactic reactions occurred. All adverse events, including four serious adverse events, were mild or moderate in intensity. Most treatment-related adverse events occurred during infusions (most commonly urticaria, vomiting, nausea, chills, pruritus, hypertension) and were resolved by infusion rate reductions and/or medication. After participation in the study, all patients, including the one who withdrew after one infusion, transitioned to commercial drug.

CONCLUSIONS:

Agalsidase beta therapy can be successfully reinstated in patients with Fabry disease who have developed IgE antibodies or skin test reactivity to the recombinant enzyme.

• Authors: David Bodensteiner, C Ronald Scott, Katherine B Sims, Gillian M Shepherd, Rebecca D Cintron, Dominique P Germain
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 10 Issue 5 Pg. 353-8 (May 2008) ISSN: 1530-0366 [Electronic] United States
• PMID: 18496035 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• Recombinant Proteins
• Immunoglobulin E
• alpha-Galactosidase
• agalsidase beta

Topics

• Adult
• Aged
• Fabry Disease (drug therapy)
• Humans
• Immunoglobulin E (blood)
• Infusions, Intravenous
• Isoenzymes (adverse effects, immunology, therapeutic use)
• Male
• Middle Aged
• Patient Selection
• Recombinant Proteins (adverse effects, immunology, therapeutic use)
• Skin Tests
• Treatment Outcome
• alpha-Galactosidase (adverse effects, immunology, therapeutic use)