Immunogenicity in Clinical Practice and Drug Development: When is it Significant?

• Published in: Clinical and translational science Vol. 13; no. 2; pp. 219 - 223
• Main Authors: Shakhnovich, Valentina, Meibohm, Bernd, Rosenberg, Amy, Kierzek, Andrzej M., Hasenkamp, Rachel, Funk, Ryan S., Thalhauser, Craig J., Graaf, Piet H., Wang, Yow‐Ming C., Hamuro, Lora
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2020; John Wiley and Sons Inc; Wiley
• Subjects: Amino acid sequence; Antigens; Bioinformatics; Biological products; Clinical medicine; Drug development; Drug dosages; Epitopes; FDA approval; Homology; Immune response; Immunoassay; Immunogenicity; Inflammatory bowel disease; Patients; Pharmacokinetics; Pharmacology; Product development; Protein engineering; Proteins; Rheumatoid arthritis; Risk assessment; Risk factors; Statistical analysis
• ISSN: 1752-8054; 1752-8062
• DOI: 10.1111/cts.12717

Statistically, up to 65% of these patients will develop ADAs during the course of IBD treatment. [...]many providers prefer proactive ADA monitoring, at least annually; however, limited insurance coverage of testing for ADAs frequently precludes this judicious practice and/or necessitates the use of different ADA assays, creating added challenges for assay interpretation. [...]with regard to incidence rates or intensity of response, the results of these assays cannot be compared between different therapeutic proteins or for the same therapeutic protein when different assays are utilized. Protein engineering is a longer‐term strategy that may be used to remove immunogenic epitopes of a protein therapeutic or in designing a therapeutic with the essential activity of an endogenous protein, but lacking in sequence homology. Because risk is a function not only of consequences, but also of probability of generating an immune response, it is important to consider the patient and protocol‐specific risk factors, as well as the critical product quality attributes that may facilitate or diminish the likelihood of ADA generation. [...]bioinformatics does not predict the impact of ADAs on pharmacokinetics (PKs) and is, therefore, not applicable to informing changes to dosing regimens and co‐therapy in the management of immunogenicity in patients.