Biologies Time Course of Immunogenicity

This highlights how the combination of formulation constituents can result in immunogenicity to the protein, and how this manifests a major concern in the 

Example Reference(s) Objective Study design/Duration Assay Outcome 

Insulin 15 Immuno-genicity of rh-insulin relative to porcine insulin 100 subjects receiving rh-insulin vs. 121 receiving porcine insulin over 12 months Species- specific binding assay -44% rh-insulin patients developed antibodies (Abs) reaching a plateau at 6 months. 60% patients receiving porcine insulin developed Abs in 12 months 

Growth hormone 16 Evaluate Abs in children treated with rh-GH and met-GH 46 GH-deficient children treated for at least 12 months (20 naive and 26 previous treatment with pituitary extracted GH) RIA Abs generated in 75% of treatment naive group within 1 year 12% of the pretreated group (only in the second year). Abs remained through duration of treatment with met-GH, but decreased and eventually become undetectable in subjects receiving rh-GH. Abs did not affect clinical efficacy 

Anti-TNF 19 Immunogenicity Review Abs generated and detected in 3-16% of patients receiving Etanercept (infliximab) within 12 months of treatment 

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