Retrospective Review of Pharmacogenetic Testing at an Academic Children’s Hospital

Abstract

There is limited evidence to support pharmacogenetic (PGx) testing in children. We conducted a retrospective review of PGx testing among 452 patients at an academic children's hospital to determine the potential utility of PGx in diseases of childhood and to identify targets for future pediatric pharmacogenetic research. An actionable gene-drug pair associated with the 28 genes tested (Clinical Pharmacogenetics Implementation Consortium (CPIC) level A or B, Pharmacogenomics Knowledge Base (PharmGKB) level 1A or B, or US Food and Drug Administration (FDA) recommendation and a PharmGKB level) was present in 98.7% of patients. We identified 203 actionable gene-drug-diagnosis groups based on the indications for each actionable drug listed in Lexicomp. Among patients with an actionable gene-drug-diagnosis group, 49.3% had a diagnosis where the drug was a therapeutic option and PGx could be used to guide treatment selection. Among patients with an associated diagnosis, 30.9% had a prescription for the actionable drug allowing PGx guided dosing. Three genes (CYP2C19, CYP2D6, and CYP3A5) accounted for all the gene-drug-diagnosis groups with matching diagnoses and prescriptions. The most common gene-drug-diagnosis groups with matching diagnoses and prescriptions were CYP2C19-citalopram-escitalopram-depression 3.3% of patients tested; CYP2C19-dexlansoprazole-gastritis-esophagitis 3.1%; CYP2C19-omeprazole-gastritis-esophagitis 2.4%; CYP2D6-atomoxetine-attention deficit hyperactivity disorder 2.2%; and CYP2C19-citalopram-escitalopram-obsessivecompulsive disorder 1.5%. PGx could be used to guide selection of current treatment options or medication dosing in almost half (48.7%) of pediatric patients tested. Mood disorders and gastritis/esophagitis are promising targets for future study of PGx testing because of the high prevalence of these diagnoses and associated actionable gene-drug pairs in the pediatric population. Pharmacogenetic (PGx) testing, specifically the inquiry into genetic variants in pharmacokinetic or pharmacodynamic pathways involved in medication metabolism or response, is commercially available and being promoted to improve patient outcomes. 1 The level of evidence supporting the clinical utility of testing for variants in individual genes differs, and translation of the test results into clinical practice is complicated. Several organizations, including the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Royal Dutch Association for the Advancement of Pharmacy-Pharmacogenetics Working Group (DPWG), have created detailed, evidence-based, gene-drug clinical

How paediatric drug development and use could benefit from OMICs: A c4c expert group white paper

“…In 15.0% of cases the PGx results could be used for dose adjustment of at least one currently prescribed drug. The two most common gene‐drug diagnosis groups with matching clinical diagnosis and prescription were mood disorders and gastritis/esophagitis, and these are therefore considered promising targets for future studies in the area of PGx testing in children and adolescents 134 …”

Pharmacogenomics for Drug Dosing in Children: Current Use, Knowledge, and Gaps

“…The National Institutes of Health–sponsored All of Us research program plans to enroll children and return pharmacogenomic results to participants 17 . Drugs with actionable pharmacogenomic dosing recommendations are frequently used in children 11,18 . Ramsey et al found that 7987‐10629 per 100 000 pediatric patients were exposed to at least 1 drug that the Clinical Pharmacogenetics Implementation Consortium (CPIC) strongly or moderately recommends a change in prescribing 11 .…”

Pharmacogenomics and health disparities, are we helping?

“…About 50% of these drugs, either the whole class or individual drugs within these classes, have not been studied in children or have limited evidence of safety in pediatric populations. Extending these recommendations to the pediatric populations and adolescents remains controversial ( Neyro et al, 2018 ; Roberts et al, 2021 ; CPIC, 2022 ). Fortunately, efforts to better understand the potential utility for PGx implementation among the pediatric population are ongoing ( Namerow et al, 2020 ; Ramsey et al, 2021 ; Roberts et al, 2021 ).…”

“…Extending these recommendations to the pediatric populations and adolescents remains controversial ( Neyro et al, 2018 ; Roberts et al, 2021 ; CPIC, 2022 ). Fortunately, efforts to better understand the potential utility for PGx implementation among the pediatric population are ongoing ( Namerow et al, 2020 ; Ramsey et al, 2021 ; Roberts et al, 2021 ). Various models have been adopted by different institutes, from single gene to panels tested either preemptively or reactively while offering point of care electronic clinical decision support (eCDS) to clinicians ( Johnson et al, 2013 ; Haidar et al, 2019 ).…”