Abstract
Subcutaneous (SC) administration of therapeutic proteins is perceived to pose higher risk of immunogenicity when compared with intravenous (IV) route of administration (RoA). However, systematic evaluations of clinical data to support this claim are lacking. This meta-analysis was conducted to compare the immunogenicity of the same therapeutic protein by IV and SC RoA. Anti-drug antibody (ADA) data and controlling variables for 7 therapeutic proteins administered by both IV and SC routes across 48 treatment groups were analyzed. RoA was the primary independent variable of interest while therapeutic protein, patient population, adjusted dose, and number of ADA samples were controlling variables. Analysis of variance was used to compare the ADA incidence between IV and SC RoA, while accounting for controlling variables and potential interactions. Subsequently, 10 additional therapeutic proteins with ADA data published for both IV and SC administration were added to the above 7 therapeutic proteins and were evaluated for ADA incidence. RoA had no statistically significant effect on ADA incidence for the initial dataset of 7 therapeutic proteins (p = 0.55). The only variable with a significant effect on ADA incidence was the therapeutic protein. None of the other controlling variables, including their interactions with RoA, was significant. When all data from the 17 therapeutic proteins were pooled, there was no statistically significant effect of RoA on ADA incidence (p = 0.81). In conclusion, there is no significant difference in ADA incidence between the IV and SC RoA, based on analysis of clinical ADA data from 17 therapeutic proteins.
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Acknowledgements
Yazdi K. Pithavala, Pfizer, also contributed suggestions for the analyses. David Potter, Pfizer, advised on the optimal statistical analysis method and aided in explanation of statistical results.
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This work was sponsored by Pfizer Inc. and funded by a grant from the University of California, San Diego Skaggs School of Pharmacy Summer Research Program.
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J.F. and Y.C. wrote the manuscript. J.F. collected and analyzed the data. L.R., M.D.V.A, D.M., and Y.C. provided the basis for the project, contributions to the analyses, as well as revisions to the manuscript.
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J.F. is a student at the University of California, San Diego Skaggs School of Pharmacy and was a summer intern at Pfizer when this work was conducted who declared no competing interests for this work. M.D.V.A., D.M., and Y.C. are employees of Pfizer Inc. and own stock in Pfizer.
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Felderman, J., Ramaiah, L., Vazquez-Abad, MD. et al. Anti-Drug Antibody Incidence Comparison of Therapeutic Proteins Administered Via Subcutaneous vs. Intravenous Route. AAPS J 26, 60 (2024). https://doi.org/10.1208/s12248-024-00930-w
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DOI: https://doi.org/10.1208/s12248-024-00930-w