CPIC Guideline Update: Carbamazepine, Oxcarbazepine and HLA genotype

The CPIC Guideline for carbamazepine, oxcarbazepine and HLA genotype is now published in Clinical Pharmacology and Therapeutics. The accepted article can be viewed on the PharmGKB pages for carbamazepine and oxcarbazepine and on the CPIC website. 

Carbamazepine and oxcarbazepine are anticonvulsants which have been approved for treatment for epilepsy and, in the case of carbamazepine, trigeminal neuralgia. Patients with the HLA-A*31:01 and/or the HLA-B*15:02 allele have a significantly increased risk of carbamazepine-induced cutaneous adverse reactions, while patients with the HLA-B*15:02 allele have a significantly increased risk of oxcarbazepine-induced cutaneous adverse reactions.

The CPIC guideline and supplement summarize evidence from the literature and provide therapeutic recommendations for carbamazepine and oxcarbazepine based on HLA genotype. This guideline is and update of the 2013 guideline for carbamazepine and HLA-B genotype and now includes prescribing information for oxcarbazepine and HLA-B and new prescribing information for carbamazepine and HLA-A genotype.

For further details see the guidelines and supplement on CPIC, or on the pages for carbamazepine and oxcarbazepine on PharmGKB.

Promote the study of Pharmacogenomics in the All of Us cohort

The NIH is collecting suggestions for what to study in a new large cohort of one million or more people living in the United States. The All of Us research program is part of the Precision Medicine Initiative and will recruit volunteers across the USA to share their data with researchers to look at big questions. NIH is seeking input from the public on what questions to address with the All of Us data and asks people to vote on the ideas they value the most.


PharmGKB has submitted some questions related to PGx that need your vote!

Idea # 363: Does collecting side-effect data directly from patients improve compliance, personalized drug choice and efficacy? After a drug has been approved, big ADRs are reported to MEDRA, but smaller side effects are not usually reported. While some may be known and in the drug label, novel side effects may occur in populations not included in the original trials. Small effects may lead to discontinuation or poor compliance. Collecting better data about side effects and combining with genomic data could give improved pharmacogenomic prediction of side effects and allow for better selection of drugs for a patient.

Idea #379: Do tailored educational materials for patient-participants undergoing pharmacogenetic testing promote patient engagement? We will assess and compare the level of understanding, engagement and satisfaction in patients who received pharmacogenetic results and are randomized to 1) a web-based portal with personalized educational content tailored to subject's results or 2)standard of care. Subjects will be surveyed to determine 1) understanding 2) engagement and 3) satisfaction. Educational content will be created by and housed at PharmGKB, in collaboration with genetic counselors and science education specialists.

There are also several more questions regarding PGx that are tagged and worth our comments and votes. Click on Pharmacogenomics in “What we are discussing” on the right hand panel.  

Curators' Favorite Papers

The first paper (Implementation of Standardized Clinical Processes for TPMT Testing in a Diverse Multidisciplinary Population: Challenges and Lessons Learned) describes the process of implementing systemwide thiopurine methyltransferase (TPMT) testing at the University of Florida Health Personalized Medicine Program (UF PMP). After the successful implementation of CYP2C19 testing for patients undergoing percutaneous coronary intervention in an inpatient setting, researchers opted to analyze test ordering patterns for TPMT in a large and more diverse group of patients. Pharamacogenetic (PGx) test results were incorporated into Electronic Health Records (EHR) using Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines. Data came over a period of three years from 834 patients for whom TPMT testing was ordered (February 2014 to February 2017). In general, enzymatic testing was ordered far more frequently than genetic testing (83% vs. 17%) and rates differed significantly (P< 0.0001) between outpatient (580) and inpatient orders (293). Significant differences were discovered between specialties with regards to TPMT test orders - for example,  hematology/oncology service providers ordered genotype testing more frequently in the inpatient setting (95% of tests from hematology/oncology vs. 60% of tests from other specialties; P< 0.0001). The study also discusses differences in testing between populations and breaks down test alert notification preferences by specialties in detail. You may find more information on TPMT, azathioprine, thioguanine,  or mercaptopurine on PharmGKB and PGx-guided dosing guidelines on PharmGKB or CPICpgx.org.

The second paper (Patient understanding of, satisfaction with, and perceived utility of whole-genome sequencing: findings from the MedSeq Project) examines patient-subject understanding of informed consent, satisfaction with disclosure of results, and perception of whole genome sequencing utility (WGS) in cardiology and primary care patients. Patient-subjects were recruited by their cardiologists (already diagnosed with hypertrophic cardiomyopathy or dilated cardiomyopathy) or primary care physicians (PCP) (healthy adults) and were randomized to give family health history (FH) alone or undergo WGS too (FH + WGS). Results were discussed with their respective physicians, who had been counseled in genetics. A majority of subjects (N = 203) were White, non-Hispanic, had completed college and had annual household incomes of over $100K. Most subjects were able to adequately describe the study and demonstrated high genetics and health literacy, as well as an understanding of informed consent and experienced a high level of satisfaction. However, some differences emerged between the FH and the FH + WGS groups: subjects in the FH + WGS group were more likely to report feeling that they had received too much information, and subjects in the FH group reported less satisfaction and more decisional regret than the FH + WGS group. The authors suspect that FH subjects may have been disappointed at not having been randomized to receive WGS results. The primary care group was also more likely to feel that they had received too much information relative to the cardiology group. The authors note that the results are encouraging but suggest that similar efforts in future studies should aim to temper subjects’ expectations regarding WGS and that studies in more diverse cohorts will be necessary.