title: Monoclonal antibodies: longitudinal prescribing information analysis of hypersensitivity reactions.
abstract: Monoclonal antibodies (mAbs) are known to cause hypersensitivity reactions (HSRs). The reactions pose a significant challenge to investigators, regulators, and health providers. Because HSRs cannot be predicted through the pharmacological basis of a therapy, clinical data are often relied upon to detect the reactions. Unfortunately, clinical studies are often unable to adequately characterize HSRs especially in therapies for orphan diseases. HSRs can go undetected until post-marketing safety surveillance when a large number of patients have been exposed to the therapy. The presented data demonstrates how hypersensitivity reaction warnings have changed over time in the prescribing information (PI), i.e., the drug package insert, through August 1, 2011 for 28 US-marketed mAbs. Tracking all PI revisions for each mAb over time revealed that hypersensitivity warning statements were expanded to include more severe manifestations. Over the course of a mAb therapy's life cycle, the hypersensitivity warning is twice more likely to be upgraded than downgraded in priority. Approximately 85% of hypersensitivity-associated fatality warnings were added in PI revisions as a result of post-marketing experience. Over 60% (20/33) of revisions to hypersensitivity warnings occurred within 3-4 y of product approval. While HSRs are generally recognized and described in the initial PI of mAbs, fatal HSRs are most commonly observed in post-marketing surveillance. Results of this study suggest that initial product labeling information may not describe rare but clinically significant occurrences of severe or fatal HSRs, but subsequent label revisions include rare events observed during post-marketed product use.
authors.affiliation: School of Pharmacy, University of Georgia, Athens, GA, USA.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kleyman
authors.forename: Debra S
authors.initials: DS
authors.lastname: Weintraub
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D017277:Drug Approval; D004342:Drug Hypersensitivity / Q000209:etiology / Q000517:prevention & control*; D004348:Drug Labeling / Q000592:standards; D019981:Health Care Sector; D006801:Humans; D008137:Longitudinal Studies; D010818:Practice Patterns, Physicians'; D011358:Product Surveillance, Postmarketing; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal