Antibody Monitoring

Antibody Monitoring
The primary objective of antibody monitoring is to better understand the formation of antibodies within the Fabry patient population receiving enzyme replacement therapy (ERT). Antibody testing for patients receiving Fabrazyme® (agalsidase beta) s provided by Genzyme. As part of the Recommended Schedule of Assessments, physicians participating in the Fabry Registry are encouraged to include antibody monitoring for their patients receiving Fabrazyme.

IgG Antibodies
Patients receiving Fabrazyme may develop IgG antibody reactivity to agalsidase beta, the active ingredient in Fabrazyme. Clinical trial data have shown that seroconversion has occurred in 73% of the Fabry patients being treated. The formation of IgG antibodies is not uncommon with intravenous protein products. Antibody development does not preclude continued treatment with Fabrazyme.

Genzyme encourages treating physicians to collect serum samples for IgG antibody testing prior to the first Fabrazyme infusion and routinely thereafter; see Recommended IgG Antibody Monitoring Schedule section below.

Recommended IgG Antibody Monitoring Schedule
Antibody monitoring is recommended for all patients receiving Fabrazyme therapy according to the following schedule:

• Prior to the first Fabrazyme infusion,
• Every 3 months for the first 18 months of treatment, then
• Every 6 months until a negative result is confirmed, and
• Annually thereafter.

Download Antibody (IgG) Testing Instructions and Requisition Form

IgE Antibodies
Some patients may experience adverse events during or shortly after a Fabrazyme infusion that are suspected to be IgE-mediated. Genzyme encourages immediate immune testing in circumstances in which the treating physician suspects the symptoms or complex of symptoms to be mediated by the formation of IgE antibodies to Fabrazyme.

If a pre-infusion serum sample is available (drawn for the purposes of routine IgG antibody monitoring), submit that serum sample immediately. It will be used for both IgG and IgE testing. If no pre-infusion serum sample is available, the patient should return no sooner than 3 days after the reactions for a serum sample to be drawn and sent for IgE antibody analysis.

A serum sample should also be drawn one to four hours after the reaction for Serum Tryptase testing as a confirmatory test to the IgE result.

These assays must be coordinated through Genzyme Pharmacovigilance. Clinical Immunology will not initiate sample testing for IgE or any other additional immunogenicity testing outside of routine IgG monitoring until medical review is received from a Genzyme Safety Officer.

Download Antibody (IgE), Serum Tryptase and Complement Instructions and Requisition Form

Monitoring for Immune Complex Mediated Syndromes
Since IgG antibody formation is very common with Fabrazyme therapy, it is recommended that there be surveillance for immune complex-mediated syndromes such as systemic lupus erythematosis, mixed cryoglobulinemias, and glomerulonephritis. Such signs and symptoms may include hematuria, proteinuria, rash, arthritis, serositis, central nervous system (CNS) complications, and hemolytic anemia, among others. It should be noted that hematuria and proteinuria are not reliable markers of immune complex disease in Fabry patients, because these patients may have these manifestations as part of their underlying disease. If patients develop signs or symptoms suggestive of immune complex disease, appropriate laboratory assessments for circulating immune complexes, such as Raji and C1q binding methods will be undertaken after consultation with a Genzyme Safety Officer.