Article
What is the influence of metabolic profiles on drug safety in routine care in Germany? – Findings from the EMPAR study
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Authors
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Steffen Heß
- BfArM, Bonn, Germany
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Michael Steffens
- BfArM, Bonn, Germany
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Jochen Fracowiak
- BfArM, Bonn, Germany
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Tatjana Hübner
- BfArM, Bonn, Germany
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Daria Langner
- Techniker Krankenkasse, Hamburg, Germany
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Marco Garling
- Techniker Krankenkasse, Hamburg, Germany
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Felix Falkenberg
- Techniker Krankenkasse, Hamburg, Germany
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Christoph Röthlein
- DZNE, Bonn, Germany
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Willy Gomm
- DZNE e.V., Bonn, Germany
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Roland Linder
- Techniker Krankenkasse, Hamburg, Germany
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Julia Stingl
- RWTH, Aachen, Germany
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Britta Hänisch
- BfArM, Bonn, Germany; DZNE, Bonn, Germany; University of Bonn, Bonn, Germany
| Published: | February 26, 2021 |
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Outline
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Background: The occurrence of adverse drug reactions (ADRs) and the individual response to drug treatment can be affected by genetic variability in metabolic profiles. The magnitude of this effect is largely unknown within a real world setting and needs to be determined in order to assess the clinical utility of pharmacogenetic testing in routine care. The EMPAR project observes the effect of metabolic profiles on drug safety directly in routine care in Germany.
Methods: To this end EMPAR is designed as a cohort study, focusing on drugs whose metabolisation is influenced by pharmacogenetic variants. Study participants are recruited from insurants of the Techniker Krankenkasse who have at least one prescriptions of a pharmacogenetically relevant drug and provide DNA samples for the analyses of metabolic profiles. The study comprises three patient groups: users of anticoagulants, statins, as well as patients who received an ICD-10 Y57.9! diagnosis of ADRs. The main objective of EMPAR is to study the influence of individual metabolic profiles on the risk of ADRs after use of a pharmacogenetically relevant drug. The enzymes of interest comprise e.g. cytochrome p450 enzymes, such as the enzymes CYP2C9, CYP2C19 and CYP3A4/5 whose genetic variants are determined from DNA samples. The occurrence of ADRs in routine care data is compared between groups of varying metabolic profiles. In further pharmacoepidemiological analyses, we identify parameters which correlate with ADRs, health care utilization, and economic outcomes.
Results: The metabolic profiles are linked it with clinically relevant information from routine care data for 7.668 users of pharmacogenetically relevant drugs. Hence, we are able to show differences in the occurrence of severe ADRs, such as bleeding and thromboembolic events for anticoagulants, depending on the combination of the type of drug and individual metabolic profiles.
Conclusion: The EMPAR study is the first to examine the effect of metabolic profiles on drug safety with German routine care data and yields insights into the clinical utility of pharmacogenetic testing in routine care.
This work was supported by the Innovation Fund of the Federal Joint Committee (grant number: 01VSF16047). The funding body reviewed and approved the design of the study. The funder is not involved in data collection, analysis or interpretation.
The authors declare that they have no competing interests.
The authors declare that a positive ethics committee vote has been obtained.
