Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme.
OBJECTIVE
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A (agalsidase beta; Fabrazyme), could be safely continued in patients with Fabry disease who had been withdrawn from a previous clinical trial as a precautionary, protocol-specified measure due to detection of serum IgE antibodies or skin-test reactivity to agalsidase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.
Bodensteiner
David
D
Division of Hematology/Oncology, University of Kansas Medical Center, Kansas City, Kansas 66205, USA. dominique.germain@rpc.aphp.fr
Scott
C Ronald
CR
Sims
Katherine B
KB
Shepherd
Gillian M
GM
Cintron
Rebecca D
RD
Germain
Dominique P
DP
D000328:Adult; D000368:Aged; D000795:Fabry Disease / Q000188:drug therapy*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007262:Infusions, Intravenous; D007527:Isoenzymes / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011994:Recombinant Proteins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D012882:Skin Tests; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use
D007527:Isoenzymes; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D000519:alpha-Galactosidase; C459420:agalsidase beta