Use of Pharmacogenetic Drugs by the Dutch Population

Abstract

Introduction The Dutch Pharmacogenetics Working Group (DPWG) indicated a list of actionable genotypes that affect patients’ response to more 50 drugs; these drugs which show variable effects based on patients’ genetic traits were named as pharmacogenetics (PGX) drugs. Preemptive genetic testing before using these drugs may protect certain patients from serious adverse reactions and could help in avoiding treatment failures. The objectives of this study include identifying the rate of PGX drug usage among Dutch population, estimating the level of users who carry the actionable genotypes and determining the main genes involved in drug’s effect variability. Methods Usage of PGX drugs over 2011–2017 by the insured population (an average of 11.4 million) in outpatient clinics in Netherlands was obtained from the publically available GIP databank. The data of 45 drugs were analyzed and their interactions with selected pharmacogenes were estimated. Frequency of actionable genotypes of 249 Dutch parents was obtained from the public database: Genome of Netherlands (GoNL), to identify the pattern of genetic characteristics of Dutch population. Results Over a 7 year period, 51.3 million exposures of patients to PGX drugs were reported with an average of 5.3 exposures per each drug user. One quarterof the exposures (12.4 million) are predicted to be experienced by individuals with actionable genotypes (risky exposures). Up to 60% of the risky exposures (around 7.5 million) were related to drugs metabolized by CYP2D6. SLCO1B1, and CYP2C19 were also identified among the top genes affecting response of drugs users (involved in about 22 and 12.4% of the risky exposures, respectively). Cardiovascular medications were the top prescribed PGX drug class (43%), followed by gastroenterology (29%) and psychiatry/neurology medications (15%). Women use more PGX drugs than men (55.8 vs. 44.2%, respectively) with the majority (84%) of users in both sexes are above 45 years. Conclusion PGX drugs are commonly used in Netherlands. Preemptive panel testing for CYP2D6, SLCO1B1, and CYP2C19 only could be useful to predict 95% of vulnerable patients’ exposures to PGX drugs. Future studies to assess the economic impact of preemptive panel testing on patients of older age are suggested.

Polypharmacy, potentially inappropriate medication and pharmacogenomics drug exposure in the Rhineland Study

“…This is in accordance with reports from the Netherlands, were 24% of the total drugs used between 2011-2017 were PGX drugs [25]. Within that Dutch population, genotyping SLCO1B1, CYP2C19 and CYP2D6 would cover all possible drug-gene interactions for 95% of the drugs used in the Netherlands [29]. Drugs that are influenced by SLCO1B1, CYP2C19 and CYP2D6 polymorphisms also caused the high prevalence of PGX drug use in our study.…”

“…We selected drugs (Appendix I), for which pharmacogenomic testing is recommended, for the following genes: CYP2C9, CYP2C19, CYP2D6, SLCO1B1 and VKORC1. We selected these genes, because polymorphisms of them are highly prevalent, and because they influence metabolism of drugs commonly taken in primary care [29,30]. Analyses were done for regularly used drugs only, and for regularly and as needed used drugs combined.…”

Implementation of Pharmacogenetics in Primary Care: A Multi-Stakeholder Perspective

“…Twenty-six of these drugs for which pharmacogenetic guidelines are available are prescribed in the primary health care setting to relatively large groups of patients (see Supplementary Table 1) (Houwink et al, 2015). It is therefore expected that many patients would benefit from PGx-based prescription policy (Alshabeeb et al, 2019).…”

Outcomes and Clinical Relevance of a 16-Gene Pharmacogenetic Panel Test for Medication Management - A Cohort Study in 135 Patients

“…1 No data on eGFR was available for x patients, calculated by using CKD-EPI creatinine formula 2 One patient with indication of tamoxifen did not take any drugs at the time of PGx testing 3 Patients with at least one inhibitor, List of considered CYP2C19 inhibitors according to mediQ provided in TableS4…”

“…n.a. = not applicable (no triggering drugs in screening patients)1 Variant = "non-normal" phenotype according to PharmGKB, phenotypes in bold = clinically relevant for triggering drug(s)2 Based on PGx results, concerned drug-gene pairs reported in TableS2…”