A comparison of post-authorization adverse events of biopharmaceuticals and small molecules within the same anatomical therapeutic chemical class

Background: The nature of adverse events (AEs) observed post authorization for biopharmaceuticals differs from chemically synthesized, small molecules. It remains unclear if this observed difference can be attributed to differences in authorized indications between the groups. Objectives: To investigate if the nature of AEs identified post-authorization for biopharmaceuticals differs from AEs of small molecules within the same Anatomical Therapeutic Chemical (ATC) class. Methods: All biopharmaceutical and small molecule products centrally approved in the European Union classified in the ATC class of “antineoplastic and immunomodulating agents” (“L”) were included. Generics and biosimilars were excluded. All safety related changes to the Summary of Product Characteristics during 2004- 2011 were analyzed; individual AEs were identified and coded according to MedDRA 14.1. Proportions of AEs within therapeutic subgroups were compared and tested using two-sided Fisher's exact tests. Results: A total of 747 AEs were identified; 361 for biopharmaceuticals and 386 for small molecules. For biopharmaceuticals, 171 (47.4%) AEs were reported for immunosuppressants, 128 (35.5%) for immunostimulants and 62 (17.2%) for antineoplastic agents. For small molecules the most AEs, 288 (74.6%), were reported for antineoplastic agents, 92 (23.8%) for immunosuppressants and 6 (1.6%) for endocrine therapies. Within the ATC subgroup of immunosuppressants, neoplasms, 20% vs. 2% (p <0.01) and infections and infestations, 22% vs. 9% (p <0.01) occurred significantly more frequent for biopharmaceuticals. AEs of small molecules were more often renal and urinary disorders, 7% vs. 0% (p <0.01), blood and lymphatic system disorders, 10% vs. 3% (p = 0.04) and vascular disorders, 7% vs. 1% (p = 0.02). In the sub group of antineoplastics, immune system disorders occurred more frequently for biopharmaceuticals, 6%vs. 1% (p = 0.04). Conclusions: The distribution of AEs identified post authorization differs for biopharmaceuticals and small molecules, even in products from the same therapeutic subgroup. This may warrant a targeted pharmacovigilance approach for biopharmaceuticals.