816 - Pharmacogenetics in Pediatric Patients with Cystic Fibrosis

Publication Number: 816.6108

Caroline Thompson, Oklahoma University- Tulsa Health Sciences Center Pediatric Residency, Tulsa, OK, United States; Michelle Condren, University of Oklahoma School of Community Medicine, Tulsa, OK, United States; Samie Sabet, University of Oklahoma College of Medicine, Tulsa, OK, United States; Amy D. Hendrix-Dicken, OU-TU School of Community Medicine, Tulsa, OK, United States; Joseph Walter, The Children's Hospital at Saint Francis, Tulsa, OK, United States; Jeffrey R. Frerking, The University of Oklahoma Health Scienc, Glenpool, OK, United States

Background: Clinical pharmacogenetics (PGx) aims to reduce variability in pharmacotherapy outcomes. However, its clinical use in pediatric care has been limited by several barriers, including unfamiliarity and lack of established protocols. People with cystic fibrosis (CF) face a higher risk of adverse drug effects due to the complex regimens they often require. Preemptive PGx testing and education at an early age could enhance the outcome of future pharmacotherapy regimens for these patients.

Objective: This research aimed to study the clinical utility of PGx testing for non-CFTR pharmacotherapy in children with CF by evaluating current and potential gene-drug interactions in the cohort.

Design/Methods: A prospective study of children 0 through 18 years with CF was conducted in a pediatric CF center. PGx testing was performed by Dynamic DNA Laboratories, Springfield, MO using a multi-gene panel, while current medications were obtained from electronic medical records. Guidelines and drug labels were used to identify actionable recommendations. Parents were educated on findings and were provided a satisfaction survey. Current and potential gene-drug interactions were grouped by drug class. Descriptive statistics were then conducted to determine frequencies and percentages of actionable genotypes as well as current/potential gene-drug interactions by drug class.

Results: A total of 40 participants were recruited. Individuals were predominantly female (n=21, 52.5%), White, non-Hispanic (n=22, 55.0%), and homozygous ΔF508 (n=23, 59.0%). Thirty percent of individuals (n=12) had 5 actionable genotypes followed by 27.5% (n=11) with 6 (Figure 1). The most common actionable genotypes observed are depicted in Figure 2. When assessing current and potential gene-drug interactions by drug class, all individuals (n=40) had genotypic variations interacting with proton pump inhibitors followed by antidepressants (n=34, 85%), and antivirals (n=34, 85%, figure 3). Of the total 1,327 total potential gene-drug interactions, only nine (0.68%) involved current medications. In these 9 instances participants were advised to discuss the findings with the prescriber.

Conclusion(s): While current gene-drug interactions were limited, numerous potential gene-drug interactions were revealed in a significant portion of the cohort particularly involving CYP2C19 and CYP2D6 pharmacogenes. This implies the value of PGx testing and education in enhancing future pharmacotherapy outcomes for medications people with CF often need in their lifetime.

Figure 1. Number of Actionable Genotypes per Person


Figure 2. Percent of Participants with Actionable Genes


Figure 3. Drug Classes with Participants Having a Current or Potential Safety and/or Efficacy Concern


Figure 1. Number of Actionable Genotypes per Person


Figure 2. Percent of Participants with Actionable Genes


Figure 3. Drug Classes with Participants Having a Current or Potential Safety and/or Efficacy Concern