Genotype-Guided Treatment and Adverse Drug Reactions

Adverse reactions to drugs refer to unexpected or harmful effects that occur as a result of taking medications. These reactions can range from mild discomfort to severe and life-threatening conditions. Common adverse reactions include allergic reactions, such as skin rashes or hives, gastrointestinal disturbances, dizziness, headaches, and changes in blood pressure.

Severe adverse reactions may involve organ damage, blood disorders, or anaphylaxis. Factors contributing to adverse reactions include individual susceptibility, drug interactions, improper dosage, or underlying medical conditions. Prompt identification and reporting of adverse reactions are crucial for ensuring patient safety and optimizing healthcare interventions. Healthcare professionals play a vital role in monitoring and managing adverse reactions to drugs.

Clinical Trial

Pharmacogenetic testing involves analyzing a person's genetics to determine their response to certain drugs and has proven beneficial for specific gene-drug combinations. However, the effectiveness of using a comprehensive pharmacogenetic panel as a pre-emptive genotyping strategy has yet to be thoroughly evaluated.

A trial was conducted across multiple European countries, including Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK. The study involved 18 hospitals, nine community health centers, and 28 pharmacies. Eligible participants were 18 or older and received their first prescription for a drug recommended by the Dutch Pharmacogenetics Working Group.

Patients with prior genetic testing for genes relevant to the prescribed medication, those with a treatment duration of less than seven consecutive days, and individuals with severe renal or liver insufficiency were excluded. Written informed consent was obtained from all participants.

The trial focused on genotyping patients for 50 variants in 12 genes. If an actionable variant was detected, meaning a drug-gene interaction that required a change in standard drug treatment according to the Dutch Pharmacogenetics Working Group's recommendations, the patients received treatment accordingly. The control group received standard treatment. Clinicians were educated on pre-emptive pharmacogenetic testing, and educational materials were available.

 

The primary outcome measured was the occurrence of clinically relevant adverse drug reactions over a 12-week follow-up period. Analyses were conducted regardless of patient adherence to the guidelines. The primary analysis compared outcomes between individuals with actionable drug-gene interactions in the study and control groups. A comprehensive analysis including all patients was performed if a statistically significant difference was found. The safety analysis included all participants who received at least one dose of the study drug.

Results

Among patients with actionable test results, clinically relevant adverse drug reactions occurred in 21.0% of the study group (152 out of 725 patients) compared to 27.7% of the control group (231 out of 833 patients). For all patients, the incidence was 21.5% (628 out of 2,923 patients) in the study group and 28.6% (934 out of 3,270 patients) in the control group.

Conclusion

Using a 12-gene pharmacogenetic panel to guide treatment significantly reduced the occurrence of clinically relevant adverse drug reactions. Moreover, this strategy was feasible across diverse European healthcare systems and settings. The findings suggest that large-scale pharmacogenetic testing implementation could enhance drug therapy safety.
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