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Immunoassay Methods Used In Clinical Studies For The Detection Of Anti-drug Antibodies To Adalimumab And Infliximab


B. Gorovits, D. J. Baltrukonis, I. Bhattacharya, M. A. Birchler, D. Finco, D. Sikkema, M. S. Vincent, S. Lula, L. Marshall, T. P. Hickl
The Journal of Translational Immunology
DOI: 10.1111/cei.13112



To examine the assay formats used to detect anti-drug antibodies (ADA) in clinical studies of the anti-TNF monoclonal antibodies adalimumab and infliximab in chronic inflammatory disease and their potential impact on pharmacokinetic and clinical outcomes.


Using findings of a recent systematic literature review of the immunogenicity of 11 biologic/biosimilar agents, we conducted an ancillary qualitative review of a subset of randomized controlled trials and observational studies of the monoclonal antibodies against anti-tumor necrosis factor adalimumab and infliximab.


Among studies of adalimumab and infliximab, the immunoassay method used to detect antibodies was reported in 91/111 (82%) and 154/206 (75%) adalimumab and infliximab studies, respectively. In most adalimumab and infliximab studies, an enzyme-linked immunosorbent assay or radioimmunoassay was used [85/91 (93%) and 134/154 (87%), respectively]. ADA incidence varied widely across assays and inflammatory diseases (adalimumab, 0–87%; infliximab, 0–79%). Pharmacokinetic and clinical outcomes were only reported for ADA-positive patients in 38/91 (42%) and 61/154 (40%) of adalimumab and infliximab studies, respectively. Regardless of assay format or biologic used, ADA formation was associated with lower serum concentrations, reduced efficacy, and elevated rates of infusion-related reactions.


Consistent with previous recommendations to improve interpretation of immunogenicity data for biologics, greater consistency in reporting of assay methods and clinical consequences of ADA formation may prove useful. Additional standardization in immunogenicity testing and reporting, application of modern, robust assays that satisfy current regulatory expectations, and implementation of international standards for marketed products may help improve our understanding of the impact of immunogenicity to biologics. This article is protected by copyright. All rights reserved.