TY - JOUR
T1 - Regulatory safety learning driven by the mechanism of action
T2 - the case of TNF-α inhibitors
AU - Minnema, Lotte A
AU - Giezen, Thijs J
AU - Hoekman, Jarno
AU - Egberts, Toine C G
AU - Leufkens, Hubert G M
AU - Gardarsdottir, Helga
N1 - Funding Information:
This research was funded with an unrestricted grant from the Dutch Medicines Evaluation Board (MEB), as part of the regulatory science collaboration between the MEB and Utrecht University.
Publisher Copyright:
© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
PY - 2021/7
Y1 - 2021/7
N2 - The summary of product characteristics (SmPCs) is an important information source that includes the adverse drug reactions (ADRs) associated with the drug. Drugs with the same mechanism of action are expected to have a similar ADR profile and thus a substantial overlap of the described ADRs in the SmPC. The objective of this study is to assess this overlap. We extracted all ADRs (excluding hypersensitivity and administration site reactions) that were described in the first and all subsequent versions of the SmPCs of all approved TNF-α inhibitors in the European Union. The Medical Dictionary for Regulatory Activities was used to characterize the ADRs. At the end of follow-up, 293 unique ADRs (at high level term level) were described in the SmPCs of the 5 TNF-α inhibitors. There was substantial variation in the number of ADRs described in the SmPC among the TNF-α inhibitors. Of the 293 ADRs, 133 (45%) were described in the SmPC of one TNF-α inhibitor and 39 (13%) in the SmPCs of all 5 TNF-α inhibitors. Serious ADRs and ADRs classified as important risks were described approximately four times more often in a second SmPC than ADRs not classified as such. In conclusion, the ADRs described in the SmPCs of the TNF-α inhibitors differ considerably in number and type. In order to adequately inform prescribers and patients, acquired knowledge of the safety profile of drugs with the same mechanism of action should increasingly be taken into account in the assessment of all drugs within the class.
AB - The summary of product characteristics (SmPCs) is an important information source that includes the adverse drug reactions (ADRs) associated with the drug. Drugs with the same mechanism of action are expected to have a similar ADR profile and thus a substantial overlap of the described ADRs in the SmPC. The objective of this study is to assess this overlap. We extracted all ADRs (excluding hypersensitivity and administration site reactions) that were described in the first and all subsequent versions of the SmPCs of all approved TNF-α inhibitors in the European Union. The Medical Dictionary for Regulatory Activities was used to characterize the ADRs. At the end of follow-up, 293 unique ADRs (at high level term level) were described in the SmPCs of the 5 TNF-α inhibitors. There was substantial variation in the number of ADRs described in the SmPC among the TNF-α inhibitors. Of the 293 ADRs, 133 (45%) were described in the SmPC of one TNF-α inhibitor and 39 (13%) in the SmPCs of all 5 TNF-α inhibitors. Serious ADRs and ADRs classified as important risks were described approximately four times more often in a second SmPC than ADRs not classified as such. In conclusion, the ADRs described in the SmPCs of the TNF-α inhibitors differ considerably in number and type. In order to adequately inform prescribers and patients, acquired knowledge of the safety profile of drugs with the same mechanism of action should increasingly be taken into account in the assessment of all drugs within the class.
UR - http://www.scopus.com/inward/record.url?scp=85098189170&partnerID=8YFLogxK
U2 - 10.1002/cpt.2127
DO - 10.1002/cpt.2127
M3 - Article
C2 - 33278830
SN - 0009-9236
VL - 110
SP - 123
EP - 131
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 1
ER -