Premium
A systematic review on disease‐drug‐drug interactions with immunomodulating drugs: A critical appraisal of risk assessment and drug labelling
Author(s) -
Jong Laura M.,
Klomp Sylvia D.,
Treijtel Nicoline,
Rissmann Robert,
Swen Jesse J.,
Manson Martijn L.
Publication year - 2022
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.15372
Subject(s) - medicine , drug , pharmacology , approved drug , disease , risk assessment , summary of product characteristics , systematic review , intensive care medicine , medline , biology , computer security , computer science , biochemistry
Aim Use of immunomodulating therapeutics for immune‐mediated inflammatory diseases may cause disease‐drug‐drug interactions (DDDIs) by reversing inflammation‐driven alterations in the metabolic capacity of cytochrome P450 enzymes. European Medicine Agency (EMA) and US Food and Drug Administration (FDA) guidelines from 2007 recommend that the DDDI potential of therapeutic proteins should be assessed. This systematic analysis aimed to characterize the available DDDI trials with immunomodulatory drugs, experimental evidence for a DDDI risk and reported DDDI risk information in FDA/EMA approved drug labelling. Method For this systematic review, the EMA list of European Public Assessment Reports of human medicine was used to select immunomodulating monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) marketed after 2007 at risk for a DDDI. Selected drugs were included in PubMed and Embase searches to extract reported interaction studies. The Summary of Product Characteristics (SPCs) and the United States Prescribing Information (USPIs) were subsequently used for analysis of DDDI risk descriptions. Results Clinical interaction studies to evaluate DDDI risks were performed for 12 of the 24 mAbs (50%) and for none of the TKIs. Four studies identified a DDDI risk, of which three were studies with interleukin‐6 (IL‐6) neutralizing mAbs. Based on (non)clinical data, a DDDI risk was reported in 32% of the SPCs and in 60% of the USPIs. The EMA/FDA documentation aligned with the DDDI risk potential in 35% of the 20 cases. Conclusion This systematic review reinforces that the risk for DDDI by immunomodulating drugs is target‐ and disease‐specific. Drug labelling information designates the greatest DDDI risk to mAbs that neutralize the effects of IL‐6, Tumor Necrosis Factor alfa (TNF‐α) and interleukin‐1 bèta (IL‐1β) in diseases with systemic inflammation.