Clinical use of pre-emptive pharmacogenetic programmes
The clinical implementation of pharmacogenetics (the study of how genetics influence individual variations
in drug response) is a key factor in the development of programmes to prevent adverse drug reactions. Yet
pharmacogenetics testing in clinics is still infrequent and is mainly reactive and focused on analysing a single drug–gene interaction. Evaluation of the implementation of pharmacogenetics in the real world is necessary. Only very few pilot studies have used a pharmacogenetics panel strategy to guide drug therapy, and mostly in patients aged over 65 years in specialised care settings in the USA. The results of these pilot studies appear promising, as decreases in hospitalisations, emergency department visits, and health-care costs were observed.
Jesse J Swen and colleagues did an open, multicentre, controlled, cluster-randomised, crossover
implementation study of a 12-gene pharmacogenetics panel covering 42 drugs (following the Dutch
Pharmacogenomics Working Group [DPWG] guidelines) deployed across seven European health-care systems
to address the potential clinical effect of using pharmacogenetics for the prevention of shortterm adverse drug reactions in real-world settings. 6944 adult patients (51·4% female, 48·6% male; median age 58·0 years, 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity, with a mean 7·88 [SD 6·6] co-medications) being treated with a drug with a clinical recommendation in the DPWG guidelines were enrolled. Participants received either genotype-guided doses (3342 [51·9%]) or standard care (3602 [48·1%]); however adherence to the DPWG recommendation was not mandatory and was left to the discretion of the treating physicians and pharmacists, but monitored). The study compared patients with an actionable drug–gene interaction test result (ie, a result for which the DPWG recommended a change to standard care drug treatment) in the intervention group (n=725) and in the control group (n=833) and reported that the risk of severe adverse drug reactions was reduced by 30% in the intervention group compared with in the control group (odds ratio [OR] 0·70; 95% CI 0·54–0·91; p=0·0075). Interestingly, when comparing all patients (n=2923 in the intervention group vs n=3270 in the control group), including those with actionable and non-actionable drug–gene interaction test results, the risk of an adverse drug reaction was also reduced by 30% (OR 0·70; 95% CI 0·61–0·79; p<0·0001). The study also highlighted that the covariant, number of concomitant medications, was associated with a significant increase in adverse drug reactions.