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Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

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420 hot topic(s) found with the query "Pharmacogenomics"

Pharmacogenomics, Race, and Treatment Outcome in Pediatric Acute Myeloid Leukemia
(Posted: May 18, 2024 4PM)

From the abstract: " Can tailoring the intensity of induction therapy mitigate racial disparities in the outcome of pediatric patients with acute myeloid leukemia (AML)? Findings: In this comparative effectiveness analysis of 86 Black and 359 White patients with AML, Black patients exhibited a higher prevalence of low cytarabine pharmacogenomic 10–single-nucleotide variant (ACS10) scores, which were associated with an unfavorable outcome after initial treatment with low-dose cytarabine-based induction therapy. Augmentation of induction therapy was associated with improved outcome for patients with low ACS10 scores and with no disparity in outcome between Black patients and White patients."

Healthcare utilization and behavior changes following workplace genetic testing at a large U.S. healthcare system
(Posted: May 08, 2024 11AM)

From the abstract: " This study explored employee health behavior changes and healthcare utilization following workplace genetic testing (wGT). Wellness program-associated wGT seeks to improve employee health, but related health implications are unknown. Methods: Employees of a large U.S. healthcare system offering wGT (cancer, heart disease, and pharmacogenomics - PGx) were sent electronic surveys. Self-reported data from those who received test results were analyzed. Descriptive statistics characterized responses, while logistic regression analyses explored correlates of responses to wGT."

Nucleic acid-based drugs for patients with solid tumours.
Sebastian G Huayamares et al. Nat Rev Clin Oncol 2024 4 (Posted: Apr 10, 2024 8AM)

From the abstract: "The treatment of patients with advanced-stage solid tumours typically involves a multimodality approach (including surgery, chemotherapy, radiotherapy, targeted therapy and/or immunotherapy), which is often ultimately ineffective. Nucleic acid-based drugs, either as monotherapies or in combination with standard-of-care therapies, are rapidly emerging as novel treatments capable of generating responses in otherwise refractory tumours. These therapies include those using viral vectors (also referred to as gene therapies), several of which have now been approved by regulatory agencies, and nanoparticles containing mRNAs and a range of other nucleotides. "

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of CYP2C9, HLA-A and HLA-B with anti-epileptic drugs.
Lisanne E N Manson et al. Eur J Hum Genet 2024 4 (Posted: Apr 04, 2024 9AM)

From the abstract: "This guideline outlines the gene-drug interaction of CYP2C9 and HLA-B with phenytoin, HLA-A and HLA-B with carbamazepine and HLA-B with oxcarbazepine and lamotrigine. A systematic review was performed and pharmacotherapeutic recommendations were developed. For CYP2C9 intermediate and poor metabolisers, the DPWG recommends lowering the daily dose of phenytoin and adjust based on effect and serum concentration after 7–10 days. For HLA-B*15:02 carriers, the risk of severe cutaneous adverse events associated with phenytoin, carbamazepine, oxcarbazepine, and lamotrigine is strongly increased. For carbamazepine, this risk is also increased in HLA-B*15:11 and HLA-A*31:01 carriers. For HLA-B*15:02, HLA-B*15:11 and HLA-A*31:01 positive patients, the DPWG recommends choosing an alternative anti-epileptic drug. "

Being precise with anticoagulation to reduce adverse drug reactions: are we there yet?
Benjamin Cross et al. Pharmacogenomics J 2024 3 (2) 7 (Posted: Mar 12, 2024 0PM)

From the abstract: "This review seeks to highlight the genetic, environmental and clinical factors associated with variability in anticoagulant response, and review the current evidence base for tailoring the drug, dose, and/or monitoring decisions to identified patient subgroups to improve anticoagulant safety. Areas that would benefit from further research are also identified. Validated variants in VKORC1, CYP2C9 and CYP4F2 constitute biomarkers for differential warfarin response and genotype-informed warfarin dosing has been shown to reduce adverse clinical events. "

Clinical impact of preemptive pharmacogenomic testing on antiplatelet therapy in a real-world setting
A Massman et al, EJHG, February 29, 2024 (Posted: Feb 29, 2024 8AM)

From the abstract: "CYP2C19 genotyping to guide antiplatelet therapy after patients develop acute coronary syndromes (ACS) or require percutaneous coronary interventions (PCIs) reduces the likelihood of major adverse cardiovascular events (MACE). Evidence about the impact of preemptive testing, where genotyping occurs while patients are healthy, is lacking. We found that preemptive genotyping had a strong impact on initial antiplatelet selection and a comparable impact on patient outcomes and healthcare utilization, compared to genotyping ordered after a need for antiplatelet therapy had been identified."

A call for increased inclusivity and global representation in pharmacogenetic testing.
April Kennedy et al. NPJ Genom Med 2024 2 (1) 13 (Posted: Feb 23, 2024 3PM)

From the abstract: "Commercial pharmacogenetic testing panels capture a fraction of the genetic variation underlying medication metabolism and predisposition to adverse reactions. In this study we compared variation in six pharmacogenes detected by whole genome sequencing (WGS) to a targeted commercial panel in a cohort of 308 individuals with family history of pediatric heart disease. In 1% of the cohort, WGS identified rare variants that altered the interpretation of metabolizer status and would thus prevent potential errors in gene-based dosing. "

Clinical implementation of preemptive pharmacogenomics in psychiatry.
Maria Skokou et al. EBioMedicine 2024 2 105009 (Posted: Feb 18, 2024 7AM)

From the abstract: "We report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder.We show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm). "

Integrating rare genetic variants into DPYD pharmacogenetic testing may help preventing fluoropyrimidine-induced toxicity.
Romain Larrue et al. Pharmacogenomics J 2024 1 (1) 1 (Posted: Jan 15, 2024 10AM)

From the abstract: "To understand the functional importance of rare genetic variants in DPYD, a pharmacogene whose alterations can cause severe toxicity in patients exposed to fluoropyrimidine-based regimens, massively parallel sequencing of the exonic regions and flanking splice junctions of the DPYD gene was performed in a series of nearly 3000 patients categorized according to pre-emptive DPD enzyme activity. "

Genomic medicine year in review: 2023.
Teri A Manolio et al. Am J Hum Genet 2023 12 (12) 1992-1995 (Posted: Dec 14, 2023 8AM)

From the article: "Highlighted papers in genomic medicine implementation research in 2023 continued several themes from earlier years, particularly in diagnostic testing of critically ill infants, genetic diagnosis of rare syndromes, and prenatal and population-based screening for monogenic syndromes. Pharmacogenomics was also highlighted with the first large-scale, multi-country clinical trial of multiple gene-drug pairs. The success of the first CRISPR-Cas9-based therapeutic trial in sickle cell disease and the independence of polygenic risk scores and family history in complex disease risk assessment were also highlighted, as were the high rate of insurance denials for exome sequencing that frequently turned out to be diagnostic. "

Should Secondary Pharmacogenomic Variants Be Actively Screened and Reported When Diagnostic Genome-Wide Sequencing Is Performed in a Child?
Jan M Friedman et al. Genet Med 2023 11 101033 (Posted: Dec 01, 2023 7AM)

From the abstract: "This white paper was prepared by the Global Alliance for Genomics and Health Regulatory and Ethics Work Stream's Pediatric Task Team to review and provide perspective with respect to ethical, legal, and social issues regarding the return of secondary pharmacogenomic variants in children who have a serious disease or developmental disorder and are undergoing exome or genome sequencing to identify a genetic cause of their condition. "

A software tool to adjust codeine dose based on CYP2D6 gene-pair polymorphisms and drug-drug interactions.
Yolande Saab et al. Pharmacogenomics J 2023 11 (Posted: Nov 09, 2023 2PM)

From the abstract: "Codeine is metabolized by the CYP2D6 enzyme, and individuals with certain genetic variations of the CYP2D6 gene may metabolize codeine differently, leading to variable efficacy and toxicity. Drug-drug interactions can also affect the metabolism of codeine. A tool to adjust codeine dose based on these factors does not currently exist. Healthcare providers should use their clinical judgment and reference different established dosing guidelines to determine the appropriate dose of codeine for individual patients. The study provides a tool that assists prescribers in adjusting codeine dose based on CYP2D6 gene-pair polymorphisms and drug-drug interactions. "

Patient-Level Exposure to Actionable Pharmacogenomic Medications in a Nationally Representative Insurance Claims Database
ML BIanchini et al, JPM, November 3, 2023 (Posted: Nov 06, 2023 10AM)

From the abstract: " The prevalence of exposure to pharmacogenomic medications is well established but little is known about how long patients are exposed to these medications. Aim: Our objective was to describe the amount of exposure to actionable pharmacogenomic medications using patient-level measures among a large nationally representative population using an insurance claims database. Methods: Our retrospective cohort study included adults (18+ years) from the IQVIA PharMetrics® Plus for Academics claims database with incident fills of 72 Clinical Pharmacogenetics Implementation Consortium level A, A/B, or B medications from January 2012 through September 2018. "

Multigenetic Pharmacogenomics-Guided Treatment vs Treatment As Usual Among Hospitalized Men With Schizophrenia: A Randomized Clinical Trial.
Zhewei Kang et al. JAMA Netw Open 2023 10 (10) e2335518 (Posted: Oct 07, 2023 8AM)

From the abstract: "What is the therapeutic efficacy of multigenic pharmacogenomics–guided treatment in patients with schizophrenia? In this randomized clinical trial that included 210 Chinese Han men, patients treated with multigenetic pharmacogenomics–guided treatment had a greater symptom improvement than those treated with treatment as usual after a 6-week treatment, measured as the mean difference in percentage change of Positive and Negative Syndrome Scale score. Meaning Multigenetic pharmacogenomic testing can be an effective tool to guide the treatment of schizophrenia. "

Frequencies of pharmacogenomic alleles across biogeographic groups in a large-scale biobank.
Binglan Li et al. Am J Hum Genet 2023 9 (Posted: Sep 28, 2023 11AM)

From the abstract: "We applied the Pharmacogenomics Clinical Annotation Tool (PharmCAT) on an integrated 200K UK Biobank genetic dataset (N = 200,044). Based on PharmCAT results, we estimated PGx frequencies (alleles, diplotypes, phenotypes, and activity scores) for 17 pharmacogenes in five biogeographic groups: European, Central/South Asian, East Asian, Afro-Caribbean, and Sub-Saharan African. PGx frequencies were distinct for each biogeographic group. Even biogeographic groups with similar proportions of phenotypes were driven by different sets of dominant PGx alleles. "

The INGENIOUS trial: Impact of pharmacogenetic testing on adverse events in a pragmatic clinical trial.
Michael T Eadon et al. Pharmacogenomics J 2023 9 (Posted: Sep 12, 2023 7AM)

From the abstract: "Adverse drug events (ADEs) account for a significant mortality, morbidity, and cost burden. Pharmacogenetic testing has the potential to reduce ADEs and inefficacy. The objective of this INGENIOUS trial (NCT02297126) analysis was to determine whether conducting and reporting pharmacogenetic panel testing impacts ADE frequency. The trial was a pragmatic, randomized controlled clinical trial, adapted as a propensity matched analysis in individuals (N?=?2612) receiving a new prescription for one or more of 26 pharmacogenetic-actionable drugs across a community safety-net and academic health system."

Assessment of clinically actionable pharmacogenetic markers to stratify anti-seizure medications.
Debleena Guin et al. Pharmacogenomics J 2023 8 (Posted: Aug 28, 2023 1PM)

From the abstract: "A total of 270 articles were retrieved with PGx evidence associated with 19 ASMs including 178 variants across 93 genes, classifying 26 genetic variants as benign/ likely benign, fourteen as drug response markers and three as risk factors for drug response. Only seventeen of these were replicated, with accuracy (up to 95%) in predicting PGx outcomes specific to six ASMs. Eight out of seventeen variants have FDA-approved PGx drug labelling for clinical implementation."

Genome-wide association study on pharmacological outcomes of musculoskeletal pain in UK Biobank.
Song Li et al. Pharmacogenomics J 2023 8 (Posted: Aug 18, 2023 7AM)

To investigate the genetic component of treatment outcome differences, we performed a genome-wide association study (GWAS) in ~23,000 participants with musculoskeletal pain from the UK Biobank. NSAID vs. opioid users were compared as a reflection of the treatment outcome of NSAIDs. We identified one genome-wide significant hit in chromosome 4 (rs549224715, P?=?3.88?×?10-8). Suggestive significant (P?<?1?×?10-6) loci were functionally annotated to 18 target genes, including four genes linked to neuropathic pain processes or musculoskeletal development.

Pharmacogenomics and the Management of Mood Disorders—A Review
KK Schaars et al, J Per Med, July 24, 2023 (Posted: Jul 25, 2023 8AM)

Today, medication selection in psychiatry relies on a trial-and-error approach based mainly on physicians’ experience. Pharmacogenetic (PGx) testing can help in this process by determining the person-specific genetic factors that may predict clinical response and side effects associated with genetic variants that impact drug-metabolizing enzymes, drug transporters or drug targets. Genetic factors can, among other things, lead to differences in the activity of enzymes that metabolize drugs.

Cost-Effectiveness Analysis in Public Health Genomics and Precision Health: Recent Findings, Methodologic Issues, and the Path Forward
CDC Public Health Genomics Webinar, October 26, 2023 Brand (Posted: Jun 09, 2023 8AM)

Dr David Veenstra from the University of Washington in Seattle will review the field as a whole and his research projects including evaluation of the cost-effectiveness of population-level genomic screening, pharmacogenomics in diverse populations, decision modeling techniques to assess evidence thresholds, and stakeholder preferences for precision medicine. He will address recent findings, methodologic issues and the path forward.

Cost-effectiveness of Pharmacogenomic Testing: How to Measure the Value of Having the Right Dose of the Right Drug for the Right Patient
L Shi et al, CDC Blog Post, May 8, 2023 Brand (Posted: May 08, 2023 4PM)

A recent systematic review that assessed the cost-effectiveness of pharmacogenetic testing for drugs with existing guidelines concluded that most studies favored pharmacogenomic testing. The significance of this conclusion must be interpreted with caution and in the context of study factors, such as funding sources, geography, cohort, and the cost-effectiveness comparisons being made.

Knowledge and attitudes of medical and pharmacy students about pharmacogenomics: a systematic review and meta-analysis.
Chen Li et al. Pharmacogenomics J 2023 5 (Posted: May 05, 2023 10AM)

Fifteen studies (5509 students; 69% [95% confidence interval (CI): 60%, 77%] females) were included. Among students, 28% [95%CI: 12, 46] had adequate PGx knowledge; 65% [95%CI: 55, 75] were willing to have PGx test for their own risk assessment; 78% [95%CI: 71, 84] had intention to incorporate PGx in future practice; and 32% [95%CI: 21, 43] were satisfied with current PGx component of curriculum. Age, advanced year of educational program, and more time spent in PGx education were positively associated with PGx knowledge and positive attitudes.

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6, CYP3A4 and CYP1A2 and antipsychotics
L Beunk et al, EJHG, March 31, 2023 (Posted: Mar 31, 2023 7AM)

Even though evidence is limited, the DPWG recommends choosing an alternative drug to treat symptoms of depression or a dose reduction for other indications for quetiapine and CYP3A4 PMs. No therapy adjustments are recommended for the other CYP2D6 and CYP3A4 predicted phenotypes. In addition, no action is required for the gene-drug combinations CYP2D6 and clozapine, flupentixol, olanzapine or quetiapine and also not for CYP1A2 and clozapine or olanzapine.

Pharmacogenomics-informed clozapine therapy.
Chad A Bousman et al. The lancet. Psychiatry 2023 2 (3) 160-162 (Posted: Feb 28, 2023 7AM)

Pharmacogenomics-informed prescribing is a strategy that leverages a person's genomic profile to inform the selection and dosing of medications, and it is typically anchored by associations between genomic variants and pharmacokinetic parameters (eg, medication plasma concentrations). Expert groups, such as the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group, have collectively developed dosing guidelines for 24 psychotropic medications.

The Promise and Challenges of Implementing Pharmacogenomics to Improve Population Health: Where Are we Heading with Preemptive Pharmacogenomic Screening?
CDC Webinar, September 14, 2023 Brand (Posted: Feb 24, 2023 8AM)

With genotyping technologies now widely available and decreasing in cost, implementing pharmacogenomics into clinical practice is widely viewed as an initial step in mainstreaming genomic medicine. The benefits of pharmacogenomic testing before starting drug therapy has been well documented for several single gene-drug combinations. In addition, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel is being rigorously assessed. However, major challenges of implementation lie at the point of integration into healthcare systems, including the modification of clinical pathways and a large knowledge gap in pharmacogenomics in the healthcare workforce.

Towards UGT1A1 guided irinotecan dosing
JK Hicks, EJHG, February 7, 2023 (Posted: Feb 08, 2023 6AM)

The DPWG concluded there was sufficiently strong evidence to recommend UGT1A1 poor metabolizers should receive an initial 30% irinotecan dose reduction to mitigate the risk of severe toxicities and titrate the dose based on tolerance. The clinical implication of this gene-drug interaction was deemed of such importance by the DPWG that UGT1A1 genotyping is considered essential for patient safety.

A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study.
Jesse J Swen et al. Lancet (London, England) 2023 2 (10374) 347-356 (Posted: Feb 06, 2023 11AM)

The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene-drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed. We found that genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organizations and settings. Large-scale implementation could help to make drug therapy increasingly safe.

Clinical Impact of the CYP2C19 Gene on Diazepam for the Management of Alcohol Withdrawal Syndrome
TT Ho et al, J Per Med, February 3, 2023 (Posted: Feb 04, 2023 7AM)

Psychiatry pharmacogenomics: Africans are not at the table.
Frances Adiukwu et al. The lancet. Psychiatry 2023 1 (2) 80 (Posted: Feb 03, 2023 7AM)

Pharmacogenomic studies have the potential to change psychiatric practice, for example by advancing precision medicine in determining medication effectiveness and thereby reducing the need for trial and error. However, the African population is under-represented with regard to data and research participation in this field, with limited output, knowledge, and clinical applicability of pharmacogenomic evidence in Africa.

Sequencing of genes of drug response in tumor DNA and implications for precision medicine in cancer patients.
Nancy Gillis et al. The pharmacogenomics journal 2023 1 (Posted: Feb 01, 2023 6AM)

Tumor DNA sequencing is becoming standard-of-care for patient treatment decisions. We evaluated genotype concordance between tumor DNA and genomic DNA from blood and catalogued functional effects of somatic mutations in 21 drug response genes in 752 solid tumor patients. Using a threshold of 10% difference between tumor and blood DNA variant allele fraction (VAF), concordance for heterogenous genotype calls was 78% and increased to 97.5% using a 30% VAF threshold. Somatic mutations were observed in all 21 drug response genes, and 44% of patients had at least one somatic mutation in these genes.

Pharmacogenomics: current status and future perspectives
M Pirmohamed, Nature Rev Genetics, January 30, 2023 (Posted: Jan 31, 2023 8AM)

Major challenges of implementation lie at the point of delivery into health-care systems, including the modification of current clinical pathways coupled with a massive knowledge gap in pharmacogenomics in the health-care workforce. Pharmacogenomics can also be used in a broader sense for drug discovery and development, with increasing evidence suggesting that genomically defined targets have an increased success rate during clinical development.

Genetic predictors of lifelong medication-use patterns in cardiometabolic diseases.
Kiiskinen Tuomo et al. Nature medicine 2023 1 (Posted: Jan 20, 2023 6AM)

Little is known about the genetic determinants of medication use in preventing cardiometabolic diseases. Using the Finnish nationwide drug purchase registry with follow-up since 1995, we performed genome-wide association analyses of longitudinal patterns of medication use in hyperlipidemia, hypertension and type 2 diabetes in up to 193,933 individuals (55% women) in the FinnGen study. In meta-analyses of up to 567,671 individuals combining FinnGen with the Estonian Biobank and the UK Biobank, we discovered 333 independent loci (P?<?5?×?10–9) associated with medication use.

Pharmacogenomics of GLP-1 receptor agonists: a genome-wide analysis of observational data and large randomised controlled trials.
Dawed Adem Y et al. The lancet. Diabetes & endocrinology 2022 12 (1) 33-41 (Posted: Dec 20, 2022 8AM)

In the treatment of type 2 diabetes, GLP-1 receptor agonists lower blood glucose concentrations, body weight, and have cardiovascular benefits. The efficacy and side effects of GLP-1 receptor agonists vary between people. Human pharmacogenomic studies of this inter-individual variation can provide both biological insight into drug action and provide biomarkers to inform clinical decision making. This genome-wide pharmacogenomic study of GLP-1 receptor agonists provides novel biological and clinical insights. Clinically, when genotype is routinely available at the point of prescribing, individuals with ARRB1 variants might benefit from earlier initiation of GLP-1 receptor agonists.

Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction of CYP2D6 and COMT with atomoxetine and methylphenidate
M Nijenhuis et al, EJHG, December 12, 2022 (Posted: Dec 12, 2022 5AM)

This guideline describes optimization of atomoxetine therapy based on genetic variation in the CYP2D6 gene. The CYP2D6 enzyme is involved in conversion of atomoxetine into the metabolite 4-hydroxyatomoxetine. With decreasing CYP2D6 enzyme activity, the exposure to atomoxetine and the risk of atomoxetine induced side effects increases. So, for patients with genetically absent CYP2D6 enzyme activity (CYP2D6 poor metabolisers), the DPWG recommends to start with the normal initial dose, bearing in mind that increasing this dose probably will not be required.

Dutch pharmacogenetics working group (DPWG) guideline for the gene–drug interaction between UGT1A1 and irinotecan
E Hulshof et al, EJHG, November 28, 2022 (Posted: Nov 28, 2022 11AM)

Gene variants leading to UGT1A1 enzyme deficiency (e.g. UGT1A1*6, *28 and *37) can be used to optimize an individual’s starting dose thereby preventing carriers from toxicity. Homozygous or compound heterozygous carriers of these allele variants are defined as UGT1A1 poor metabolisers (PM). DPWG recommends a 70% starting dose in PM patients and no dose reduction in IM patients who start treatment with irinotecan. Based on the DPWG clinical implication score, UGT1A1 genotyping is considered “essential”, indicating that UGT1A1 testing must be performed prior to initiating irinotecan treatment.

Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder.
Joas Erik et al. The pharmacogenomics journal 2022 11 (Posted: Nov 06, 2022 8AM)

We used Swedish national registry data 2005–2017 on dispensed medications and inpatient care to estimate risks for early-treatment persistence, treatment discontinuation, switching to a new antidepressant medication, and mania within 3 months of treatment initiation in patients treated with citalopram, escitalopram, sertraline, amitriptyline, and clomipramine. Metabolic phenotypes of CYP2C19 were not robustly associated with the investigated treatment outcomes based on dispense patterns. Slower metabolism was associated with an increased risk of treatment emergent mania for sertraline (hazard ratio [HR]?=?1.3, 95% CI?=?1.04–1.62, p?=?0.02) and the tricyclic antidepressants amitriptyline and clomipramine (HR?=?1.46, 95% CI?=?1.05–2.02, p?=?0.024).

Type 2 Diabetes
E Ahmad et al, The Lancet, November 2022 (Posted: Nov 02, 2022 6AM)

Type 2 diabetes accounts for nearly 90% of the approximately 537 million cases of diabetes worldwide. Access to novel therapies improves person-centred outcomes beyond glycaemic control. Precision medicine, including multiomics and pharmacogenomics, hold promise to enhance understanding of disease heterogeneity, leading to targeted therapies. Technology might improve outcomes, but its potential is yet to be realised. Despite advances, substantial barriers to changing the course of the epidemic remain.

The NHS’s new strategy for genomics: Five key takeaways
UK Genomics Education Program, October 25, 2022 (Posted: Oct 30, 2022 0PM)

We look at the new ‘Accelerating genomic medicine in the NHS’ report, an ambitious first in genomics strategy for the health service, and what it means for healthcare professionals. Here are five things we learned from the report: 1. WES out, WGS in, for children in intensive care. 2. Pharmacogenomics’ growing role. 3. Creating a new digital infrastructure. 4. Representing the patient voice. 5. Genomics upskilling for all.

Clinical utility of pharmacogenetics in a psychiatric and primary care population
KN Bohlen et al, The PGX Journal, October 27, 2022 (Posted: Oct 27, 2022 9AM)

This study evaluated the timing, use, and clinical outcomes of a pharmacogenomic panel in a healthcare setting with patients managed by primary care providers or by psychiatrists. Participants were randomized to receive a pharmacogenetics report at four weeks or 12 weeks. We found that mental quality of life, depression severity, and clinical outcomes were improved by pharmacogenomic testing regardless of provider type, with earlier testing improving outcomes sooner.

Nine-gene pharmacogenomics profile service: The Mayo Clinic experience.
Matey Eric T et al. The pharmacogenomics journal 2021 10 (1) 69-74 (Posted: Oct 22, 2022 0PM)

Eighty-two healthy individuals aged 18 and older underwent genotyping of CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLCO1B1, HLA-B*58:01, and VKORC1. A PGx pharmacist was involved in ordering, meeting with patients, interpreting, reviewing, and documenting results. Ninety three percent were CYP1A2 rapid metabolizers, 92% CYP3A4 normal metabolizers, and 88% CYP3A5 poor metabolizers; phenotype frequencies for CYP2C19 and CYP2D6 varied. Seventy-three percent had normal functioning SLCO1B1 transporter, 4% carried the HLA-B*58:01 risk variant, and 35% carried VKORC1 and CYP2C9 variants that increased warfarin sensitivity.

Do genetics contribute to TNF inhibitor response prediction in Psoriatic Arthritis?
PDK Curry et al, The PGX Journal, October 15, 2022 (Posted: Oct 17, 2022 7AM)

Drug genetic associations with COVID-19 manifestations: a data mining and network biology approach
D Charitou et al, J PGX Journal, September 29, 2022 (Posted: Sep 29, 2022 9AM)

We statistically construct a pharmacogenetic/biomarker network with significant drug-gene interactions originating from gene-disease associations. Investigation of the predicted pharmacogenes encompassing the gene-disease-gene pharmacogenomics (PGx) network suggests that these genes could play a significant role in COVID-19 clinical manifestation due to their association with autoimmune, metabolic, neurological, cardiovascular, and degenerative disorders.

The genetic landscape of major drug metabolizing cytochrome P450 genes—an updated analysis of population-scale sequencing data
Y Zhou et al, The PGX journal, September 6, 2022 (Posted: Sep 06, 2022 7AM)

Genes encoding cytochrome P450 enzymes (CYPs) are extremely polymorphic and multiple CYP variants constitute clinically relevant biomarkers for the guidance of drug selection and dosing. We previously reported the distribution of the most relevant CYP alleles using population-scale sequencing data. Here, we update these findings by making use of the increasing wealth of data, incorporating whole exome and whole genome sequencing data from 141,614 unrelated individuals across 12 human populations.

Dutch pharmacogenetics working group guideline for the gene-drug interaction of ABCG2, HLA-B and Allopurinol, and MTHFR, folic acid and methotrexate
KH van der Pol et al, EJHG, September 2, 2022 (Posted: Sep 02, 2022 9AM)

This guideline describes the gene-drug interaction of ABCG2 with allopurinol, HLA-B with allopurinol, MTHFR with folic acid, and MTHFR with methotrexate, relevant for the treatment of gout, cancer, and rheumatoid arthritis. A systematic review was performed based on which pharmacotherapeutic recommendations were developed.

A Systematic Review of Polygenic Models for Predicting Drug Outcomes
A Siemens et al, J Per Med, August 29, 2022 (Posted: Aug 30, 2022 7AM)

The search uncovered 89 papers that incorporated pharmacogenetic variants in the development of polygenic models. It was found that the most common polygenic models were constructed for drug dosing predictions in anticoagulant therapies (n = 27). While nearly all studies found a significant association with their polygenic model and the investigated drug outcome (93.3%), less than half (47.2%) compared the performance of the polygenic model against clinical predictors, and even fewer (40.4%) sought to validate model predictions in an independent cohort.

Development and Validation of the Minnesota Assessment of Pharmacogenomic Literacy (MAPLTM)
JD Allen et al, J Per Med, August 29, 2022 (Posted: Aug 30, 2022 7AM)

Ensuring that patients have an adequate understanding of pharmacogenomic (PGx) test results is a critical component of implementing precision medicine into clinical care. However, no PGx-specific validated literacy assessment has yet been developed. To address this need, we developed and validated the Minnesota Assessment of Pharmacogenomic Literacy (MAPLTM). Foundational work included a scoping review of patient and general public attitudes and experiences with pharmacogenomic testing, three focus groups, readability assessments, and review by experts and members of the general public. This resulted in a 15-item assessment designed to assess knowledge in four domains.

Pharmacogenetics of Cardiovascular Prevention in Diabetes: From Precision Medicine to Identification of Novel Targets
ML Morieri et al, J Per Medicine, August 29,2022 (Posted: Aug 29, 2022 1PM)

Development of an extensive workflow for comprehensive clinical pharmacogenomic profiling: lessons from a pilot study on 100 whole exome sequencing data
A Tafazoli et al, The PGX Journal, August 13 , 2022 (Posted: Aug 13, 2022 6PM)

This pilot study is aimed at implementing an approach for comprehensive clinical pharmacogenomics (PGx) profiling. Fifty patients with cardiovascular diseases and 50 healthy individuals underwent whole-exome sequencing. Data on 1800 PGx genes were extracted and analyzed through deep filtration separately. Theoretical drug induced phenoconversion was assessed for the patients, using sequence2script. In total, 4539 rare variants (including 115 damaging non-synonymous) were identified.

TPMT and NUDT15 Genotyping Recommendations: A Joint Consensus Recommendation of the Association for Molecular Pathology, Clinical Pharmacogenetics Implementation Consortium, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, European Society for Pharmacogenomics and Personalized Therapy, and Pharmacogenomics Knowledgebase.
Pratt Victoria M et al. The Journal of molecular diagnostics : JMD 2022 8 (Posted: Aug 09, 2022 8AM)

This document series provides recommendations for a minimum panel of variant alleles ("Tier 1") and an extended panel of variant alleles ("Tier 2") that will aid clinical laboratories when designing assays for PGx testing. The AMP PGx Working Group considered functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, as well as other technical considerations for PGx testing when developing these recommendations.

A blockchain-based framework to support pharmacogenetic data sharing
F Albalwy et all, The PGX journal, July 22, 2022 (Posted: Jul 22, 2022 8AM)

The successful implementation of pharmacogenetics (PGx) into clinical practice requires patient genomic data to be shared between stakeholders in multiple settings. This creates a number of barriers to widespread adoption of PGx, including privacy concerns related to the storage and movement of identifiable genomic data. Informatic solutions that support secure and equitable data access for genomic data are therefore important to PGx. Here we propose a methodology that uses smart contracts implemented on a blockchain-based framework, PGxChain, to address this issue.

Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder The PRIME Care Randomized Clinical Trial
DW Oslin et al, JAMA, July 12, 2022 (Posted: Jul 12, 2022 0PM)

Does provision of pharmacogenomic testing for drug-gene interactions affect selection of antidepressant medication and response of depressive symptoms in patients with major depressive disorder (MDD)? In this randomized clinical trial that included 1944 patients with MDD, provision of pharmacogenomic tests for drug interactions compared with usual care resulted in prescriptions with no predicted drug-gene interactions in 45% vs 18%, respectively, a difference that was statistically significant. Remission of symptoms reached a maximum difference of 16.5% vs 11.2% at 12 weeks but was not significantly different at 24 weeks.

miRNAs as potential diagnostic biomarkers and pharmacogenomic indicators in psychiatric disorders.
Tsermpini Evangelia Eirini et al. The pharmacogenomics journal 2022 6 (Posted: Jun 28, 2022 7AM)

We provide herein a detailed overview of circulating miRNAs and their expression profiles as biomarkers in schizophrenia, bipolar disorder and major depressive disorder and their role in response to specific treatments. Bioinformatics analysis of miR-34a, miR-106, miR-134 and miR-132, which are common among SZ, BD and MDD patients, showed brain enrichment and involvement in the modulation of critical signaling pathways, which are often deregulated in psychiatric disorders. We propose that specific miRNAs support accurate diagnosis and effective precision treatment of psychiatric disorders.

Pharmacogenomics of Clozapine-induced agranulocytosis: a systematic review and meta-analysis.
Islam Farhana et al. The pharmacogenomics journal 2022 6 (Posted: Jun 20, 2022 10AM)

Results showed that individuals carrying the HLA-DRB1*04:02 allele had nearly sixfold (95% CI 2.20–15.80, pcorrected?=?0.03) higher odds of CIA with a negative predictive value of 99.3%. Previously unreplicated alleles, TNFb5, HLA-B*59:01, TNFb4, and TNFd3 showed significant associations with CIA after multiple-testing corrections. Our findings suggest that a predictive HLA-DRB1*04:02-based pharmacogenomic test may be promising for clinical implementation but requires further investigation.

Using genomics to improve drug prescribing
L Blackburn, PHG Foundation, April 2022 (Posted: May 12, 2022 10AM)

Some pharmacogenomic testing is already available. An NHS England pharmacogenetics test evaluation working group reviews evidence for the potential inclusion of new pharmacogentic tests in the National Genomic Medicine Test Directory. The report identified a number of barriers towards wider adoption of pharmacogenomic tests, including making the most of research evidence, poor availability of tests, health professional education and engagement, and making pharmacogenomic information readily available, for example through electronic systems.

Point of care CYP2C19 genotyping after percutaneous coronary intervention
LM Baudhuin et al, The PGX Journal, April 20, 2022 (Posted: Apr 22, 2022 0PM)

Genetic screening can improve drug prescribing- Most people carry at least one mutation that can stop a drug working properly
The Economist, April 16, 2022 (Posted: Apr 14, 2022 1PM)

Peter ley, a retired civil servant who lives in London, was diagnosed with colon cancer in 2017. An operation to remove the tumour was successful. But the chemotherapy that followed caused a severe reaction that required a two-week hospital stay and a pause in his cancer treatment. All that could have been avoided had a simple test been done. The test examines a gene that encodes a liver enzyme called dihydropyrimidine dehydrogenase (or dpd for short).

Using Pharmacogenomics to Better Understand the Role of Selected Medications and Birth Defect Risk
M Jenkins et al, CDC Blog Post, April 12, 2022 Brand (Posted: Apr 12, 2022 2PM)

The NBDPS allows researchers to investigate gene-medication associations because it collected information on the timing, duration, and frequency of medication use, and has a diverse racial and ethnic study population, representative of the population of the United States. Analyzing GWAS data from this unique dataset could lead to improvements in health equity for medication safety for pregnant women. These analyses are expected to advance precision medicine by identifying individuals with higher genetic risk for birth defects via polygenic risk scores, as well as identifying medication targets.

Tracking the Scientific Literature on the Impact of Pharmacogenomics on Clinical Practice and Public Health
S Abrishamcar et al, CDC blog Post, April 4 2022 Brand (Posted: Apr 04, 2022 2PM)

Our office has created a comprehensive resource to help researchers, providers, and policy makers track progress and impact of genomics and precision health on population health. The resource features a continuously updated and curated database of scientific literature and other information. One component of this resource is a specific PGx database that focuses on progress in PGx in clinical practice and population health. A quick examination of our PGx database shows significant growth in translation and implementation science in the last decade. The number of published studies in these areas increased from 12 in 2012 to 333 in 2021.

Combining familial hypercholesterolemia and statin genetic studies as a strategy for the implementation of pharmacogenomics. A multidisciplinary approach
LR Cela et al, The PGX journal, March 31, 2022 (Posted: Apr 02, 2022 8AM)

We have implemented a new NGS strategy that combines a panel of genes related to familial hypercholesterolemia with genomic regions related to the pharmacogenomics of lipid-lowering drugs described in clinical practice guidelines and in EMA and FDA drug labels. A multidisciplinary team of doctors, biologists, and pharmacists creates a clinical report that provides diagnostic and therapeutic findings using a knowledge management and clinical decision support system, as well as an algorithm for treatment selection.

Implementation of pharmacogenomic clinical decision support for health systems: a cost-utility analysis
S Jiang et al, The PGX journal, April 1, 2022 (Posted: Apr 02, 2022 8AM)

We constructed a cost-effectiveness model to assess the clinical and economic value of a CDS alert program that provides pharmacogenomic (PGx) testing results, compared to no alert program in acute coronary syndrome (ACS) and atrial fibrillation (AF), from a health system perspective. We defaulted that 20% of 500,000 health-system members between the ages of 55 and 65 received PGx testing for CYP2C19 (ACS-clopidogrel) and CYP2C9, CYP4F2 and VKORC1 (AF-warfarin) annually. Clinical events, costs, and quality-adjusted life years (QALYs) were calculated over 20 years with an annual discount rate of 3%. In total, 3169 alerts would be fired. The CDS alert program would help avoid 16 major clinical events and 6 deaths for ACS; and 2 clinical events and 0.9 deaths for AF.

A systematic review on the cost effectiveness of pharmacogenomics in developing countries: implementation challenges
A Sukri et al, The PGX Journal, March 22, 2022 (Posted: Mar 25, 2022 7AM)

Assessing Pharmacogenetic Variation in the United States to Enhance Health Equity of Pharmacogenetic Testing
L Kalman, CDC Blog Post, March 15, 2022 Brand (Posted: Mar 15, 2022 0PM)

Most population-based genetic studies, including those examining pharmacogenetic loci, have been conducted primarily on individuals of European ancestry. This could cause health inequities because the results of PGx tests that were designed based on allele frequencies of Europeans are being applied to patients of other ethnicities, causing physicians to prescribe drugs and doses that are ineffective or may cause adverse reactions. To obtain a more complete picture of the pharmacogenetic alleles present in a diverse US population, approximately 5,000 DNA samples from the population-based NHANES will be tested to determine the PGx allele frequencies of 970 unique haplotypes in 150 pharmacogenes. The NHANES sample sets represent the US population and are over-sampled for persons aged 60 and older, African American, Asian, and Hispanics.

Comparison of FDA Table of Pharmacogenetic Associations and Clinical Pharmacogenetics Implementation Consortium guidelines.
Pritchard Daryl et al. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists 2022 (Posted: Mar 05, 2022 7AM)

In this report, we compare PGx information in the US Food and Drug Administration (FDA) Table of Pharmacogenetic Associations with information presented in Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines.Information from CPIC guidelines and the FDA Table of Pharmacogenetic Associations do not have a high level of concordance. Many drugs mentioned in CPIC guidelines are not listed in the FDA table and vice versa, and the same gene-drug association and dosing recommendation was reported for only 5 of the 126 drugs included in either source. Furthermore, classification of drugs in specific sections of the FDA table does not correlate well with CPIC-assigned or provisionally assigned clinical actionability levels.

Pharmacogenetic interventions to improve outcomes in patients with multimorbidity or prescribed polypharmacy: a systematic review
J Oshea et al, The PGX Journal, February 2022 (Posted: Feb 25, 2022 9AM)

Pharmacogenetics has potential as a component of medicines optimisation. Studies involving multi-medicine pharmacogenetics in adults with multimorbidity or polypharmacy, reporting on outcomes derived from relevant core outcome sets, were included in this systematic review. Narrative synthesis was undertaken to summarise the data; meta-analysis was inappropriate due to study heterogeneity. Fifteen studies of diverse design and variable quality were included. A small, randomised study involving pharmacist-led medicines optimisation, including pharmacogenetics, suggests this approach could have significant benefits for patients and health systems. However, due to study design heterogeneity and the quality of the included studies, it is difficult to draw generalisable conclusions.

HLA-B*07:02 and HLA-C*07:02 are associated with trimethoprim-sulfamethoxazole respiratory failure
JL Goldman et al, The PGX journal, February 2022 (Posted: Feb 22, 2022 8AM)

We have identified an underrecognized severe adverse drug reaction (ADR) of trimethoprim-sulfamethoxazole (TMP-SMX) associated respiratory failure in previously healthy children and young adults. We investigated potential genetic risk factors associated with TMP-SMX induced respiratory failure in a cohort of seven patients. We explored whole genome sequence among seven patients representing nearly half of all reported cases worldwide and 63 unrelated control individuals. All cases were either heterozygous (carriers) or homozygous for the common HLA-B*07:02–HLA-C*07:02 haplotype. Our results suggests that HLA-B*07:02 and HLA-C*07:02 are necessary for a patient to develop respiratory failure due to TMP-SMX.

Association of ITPA gene polymorphisms with adverse effects of AZA/6-MP administration: a systematic review and meta-analysis
E Barba et al, The PGX journal, January 18, 2022 (Posted: Jan 18, 2022 7AM)

Azathioprine (AZA) and its metabolite, mercaptopurine (6-MP), are widely used immunosuppressant drugs. Polymorphisms in genes implicated in AZA/6-MP metabolism, reportedly, could account in part for their potential toxicity. In the present study we performed a systematic review and a meta-analysis, comprising 30 studies and 3582 individuals, to investigate the putative genetic association of two inosine triphosphatase (ITPA) polymorphisms with adverse effects in patients treated with AZA/6-MP.

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2C19 and CYP2D6 and SSRIs
JMJL Brouwer et al, EJHG, November 16, 2021 (Posted: Nov 16, 2021 8AM)

Evidence-based dose recommendations were obtained, based on a structured analysis of published literature. In CYP2C19 PM patients, escitalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 75% of the normal maximum dose. Escitalopram should be avoided in UM patients. In CYP2C19 PM patients, citalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 70% (65–75%) of the normal maximum dose. In contrast to escitalopram, no action is needed for CYP2C19 UM patients. In CYP2C19 PM patients, sertraline dose should not exceed 37.5% of the normal maximum dose. No action is needed for CYP2C19 IM and UM patients. In CYP2D6 UM patients, paroxetine should be avoided. No action is needed for CYP2D6 PM and IM patients. In addition, no action is needed for the other gene-drug combinations.

Precision Medicine for Your Practice: Exploring Pharmacogenomic Testing
The Jackson Labs Online Course, 2021 (Posted: Nov 08, 2021 8AM)

Precision Medicine for Your Practice is a series of short (30 minute), online modules covering specific topics in genomics and precision medicine. In this module, Exploring Pharmacogenomic Testing, you will learn about the benefits and limitations of pharmacogenomic testing, how to determine whether pharmacogenomic testing is appropriate for the patient and the application of test results to patient management.

Underrepresented patient views and perceptions of personalized medication treatment through pharmacogenomics
L Solzbery et al, NPJ Genomic Medicine, November 2021 (Posted: Nov 04, 2021 11AM)

We compared views and experiences from self-reported White and Black patients, including education level as a covariate across analyses. Black patients were less confident about whether their providers made personalized treatment decisions, and overwhelmingly wanted a greater role for their genetic information in clinical care. Both groups similarly reported that providers asked their opinions regarding medication changes, but White patients were more likely (59% vs. 49%, P?=?0.005) to discuss the impact of personal/genetic makeup on medication response with providers, and Black patients reported initiating such discussions much less frequently (4% vs. 15%, P?=?0.037).

Nine-gene pharmacogenomics profile service: The Mayo Clinic experience
ET Matey et al, The PGX Journal, October 19, 2021 (Posted: Oct 20, 2021 1PM)

Eighty-two healthy individuals aged 18 and older underwent genotyping of CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLCO1B1, HLA-B*58:01, and VKORC1. A PGx pharmacist was involved in ordering, meeting with patients, interpreting, reviewing, and documenting results. Ninety three percent were CYP1A2 rapid metabolizers, 92% CYP3A4 normal metabolizers, and 88% CYP3A5 poor metabolizers; phenotype frequencies for CYP2C19 and CYP2D6 varied. Seventy-three percent had normal functioning SLCO1B1 transporter, 4% carried the HLA-B*58:01 risk variant, and 35% carried VKORC1 and CYP2C9 variants that increased warfarin sensitivity. Pre-emptive PGx testing offered medication improvement opportunity in 56% of participants for commonly used medications.

Impact of genetic variation in CYP2C19, CYP2D6, and CYP3A4 on oxycodone and its metabolites in a large database of clinical urine drug tests
G Zhu et al, Pharmacogenomics Journal, September 2021 (Posted: Sep 04, 2021 10AM)

Urine drug testing (UDT) is a tool for monitoring drug use, including oxycodone. While variation in cytochrome P450 (CYP) genes is known to alter oxycodone metabolism, its impact on UDT results of oxycodone and its metabolites has not been well-studied. Here, multivariate analysis was performed on retrospective UDT results of 90,379 specimens collected from 14,684 genotyped patients prescribed oxycodone. Genetic variation in CYP2D6 and CYP2C19 had a significant impact on oxymorphone/oxycodone ratios, with a 6.9-fold difference between CYP2D6 ultrarapid metabolizers (UMs) and poor metabolizers.

What is pharmacogenomics?
CB de Villiers, PHG Foundation, August 2021 (Posted: Aug 26, 2021 7AM)

Pharmacogenomics, a branch of precision medicine, is the study of genomic characteristics that affect how individuals respond to drugs. It could be useful for improving treatment for a wide variety of conditions such as depression, schizophrenia, heart disease, diabetes, cancer, and infectious diseases.

Appraisal and development of evidence-based clinical decision support to enable perioperative pharmacogenomic application
BA Borden et al, The Pharmacogenomics Journal, August 10, 2021 (Posted: Aug 10, 2021 3PM)

Variable responses to medications complicates perioperative care. As a potential solution, we evaluated and synthesized pharmacogenomic evidence that may inform anesthesia and pain prescribing to identify clinically actionable drug/gene pairs. Clinical decision-support (CDS) summaries were developed and were evaluated using Appraisal of Guidelines for Research and Evaluation (AGREE) II.

Multisite investigation of strategies for the clinical implementation of pre-emptive pharmacogenetic testing.
Duarte Julio D et al. Genetics in medicine : official journal of the American College of Medical Genetics 2021 7 (Posted: Jul 21, 2021 8AM)

We compare and contrast implementation strategies for pre-emptive PGx testing by 15 early-adopter institutions. We surveyed these groups, collecting data on testing approaches, team composition, and workflow dynamics, in addition to estimated third-party reimbursement rates. We found that while pre-emptive PGx testing models varied across sites, institutions shared several commonalities, including methods to identify patients eligible for testing, involvement of a precision medicine clinical team in program leadership, and the implementation of pharmacogenes with guidelines available.

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction between CYP2D6 and opioids (codeine, tramadol and oxycodone)
M Matic et al, The Pharmacogenomics Journal, July 15, 2021 (Posted: Jul 16, 2021 7AM)

The current Dutch Pharmacogenetics Working Group (DPWG) guideline, describes the gene–drug interaction between CYP2D6 and the opioids codeine, tramadol and oxycodone. CYP2D6 genotype is translated into normal metaboliser (NM), intermediate metaboliser (IM), poor metaboliser (PM) or ultra-rapid metaboliser (UM).

Economic evaluation in psychiatric pharmacogenomics: a systematic review
K Karamperis et al, The Pharmacogenomics Journal, July 2, 2021 (Posted: Jul 03, 2021 7AM)

Of the 18 studies evaluations, 16 studies (88.89%) drew conclusions in favor of PGx testing, of which 9 (50%) genome-guided interventions were cost-effective and 7 (38.9%) were less costly compared to standard treatment based on cost analysis. More precisely, supportive evidence exists for CYP2D6 and CYP2C19 drug–gene associations and for combinatorial PGx panels, but evidence is limited for many other drug–gene combinations.

Pharmacogenomics: From Precision Medicine to Precision Public Health
CDC webinar, October 7, 2021 Brand (Posted: Jun 29, 2021 8AM)

Advances in pharmacogenomics continue to occur at a rapid pace and promise a new era of personalized interventions for disease treatment and prevention. In this seminar, we explore the evolution of the field from basic science discoveries to clinical and population health applications.

New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin
X Liu et al, The Pharmacogenomics Journal, June 22, 2021 (Posted: Jun 23, 2021 8AM)

This study aims to identify new genetic variants associated with MACE end point during the 18-month follow-up period by a two-stage large-scale sequencing data, including high-depth whole exome sequencing of 168 patients in the discovery cohort and high-depth targeted sequencing of 1793 patients in the replication cohort. We discovered eight new genotypes and their genes associated with MACE in patients with ACS.

Side effect prediction based on drug-induced gene expression profiles and random forest with iterative feature selection
A Cakir et al, The Pharmacogenomics Journal, June 21, 2021 (Posted: Jun 23, 2021 8AM)

In this study, we addressed the common side effects of chemotherapeutics, namely alopecia, diarrhea and edema. A strategy based on Random Forest algorithm unveiled an expression signature involving 40 genes that predicted these side effects with an accuracy of 89%.

The impact of pharmacogenetic testing in patients exposed to polypharmacy: a scoping review
EL Meaddough et al, The Pharmacogenomics Journal, June 17,2021 (Posted: Jun 18, 2021 6AM)

Six studies were reviewed. Five reported improved clinical outcomes, reduced side effects, reduction in the number of drugs used, or reduced healthcare utilization. The reviewed studies varied in methodological quality, risk of bias, and outcome measures. Age, diet, disease state, and treatment adherence also influence drug response, and may confound the relationship between genetic polymorphisms and treatment outcomes.

Genetic-guided pharmacotherapy for venous thromboembolism: a systematic and critical review of economic evaluations
KK Lim et al, Pharmacogenomics Journal, June 15, 2021 (Posted: Jun 16, 2021 8AM)

The ten eligible studies, all model-based, examined heterogeneous interventions and comparators. Findings varied widely; testing was cost-saving in two base-cases, cost-effective in four, not cost-effective in three, dominated in one. Of 22 model variables that changed decisions about cost-effectiveness, effectiveness/relative effectiveness of the intervention was the most frequent, albeit of poor quality.

Determining the potential clinical value of panel-based pharmacogenetic testing in patients with chronic pain or gastroesophageal reflux disease
AL Elchynsky et al, The PGx journal, June 3, 2021 (Posted: Jun 04, 2021 11AM)

We aimed to determine the potential value of panel-based pharmacogenetic (PGx) testing in patients with chronic pain or gastroesophageal reflux disease (GERD) who underwent single-gene PGx testing to guide opioid or proton pump inhibitor (PPI) therapy, respectively. Of 448 patients included (chronic pain, n?=?337; GERD, n?=?111), mean age was 57 years, 68% were female, and 73% were white. Excluding opiates for the pain cohort and PPIs for the GERD cohort, 76.6% of patients with pain and 71.2% with GERD were prescribed at least one additional medication with a high level of PGx evidence, most commonly ondansetron or selective serotonin reuptake inhibitors.

Clinical Implications of Pharmacogenomic Testing in the Real World—Insights From a Pediatric Program
CC Coffinier, JAMA Network Open, May 26, 2021 (Posted: May 27, 2021 7AM)

One challenge identified in general PGx implementation, which may be magnified in the pediatric setting, is that the full benefit of acquiring PGx test results may not be apparent until later in life. Integrating PGx information into electronic health records and ensuring its high visibility using reminders and alerts are fundamental steps to facilitate future use; otherwise, even a simple change in clinicians within the same health care system is likely to result in the loss of information.

Assessment of the Implementation of Pharmacogenomic Testing in a Pediatric Tertiary Care Setting
I Cohn et al, JAMA Network Open, May 26, 2021 (Posted: May 27, 2021 7AM)

In this cohort study of 172 pediatric patients, pharmacogenomic testing of 6 pharmacogenes (CYP2D6, CYP2C9, CYP2C19, CYP3A5, TPMT, and VKORC1) provided results that warranted deviation from standard treatment regimens in approximately 40% of patients in the point-of-care evaluation of targeted drugs and 80% of patients in the preemptive evaluation of a broader range of drugs for potential therapy.

Implementation of Pharmacogenomic Information on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.
Tsukagoshi Eri et al. Frontiers in medicine 2021 8644154 (Posted: Apr 16, 2021 10AM)

This mini-review summarizes pharmacogenomic information on drug labels of five drugs in six countries and compared descriptions of drug labels and CPIC guidelines. Finally, we discuss future perspectives of this issue. Pharmacogenomic information on drug labels is not well-harmonized across countries/regions.

Pharmacogenomics in the Era of Next Generation Sequencing - from Byte to Bedside.
Russell Laura E et al. Drug metabolism reviews 2021 1-79 (Posted: Apr 09, 2021 10AM)

we provide an update of the functional impacts of rare pharmacogenetic variability and how this information can be leveraged to improve pharmacogenetic guidance. Furthermore, we critically discuss the current status of implementation of pharmacogenetic testing across drug development and layers of care. We identify major gaps and provide perspectives on how these can be minimized to optimize the utilization of NGS data.

Pharmacogenomics in Pain Management: A Review of Relevant Gene-Drug Associations and Clinical Considerations.
Brandl Emily et al. The Annals of pharmacotherapy 2021 10600280211003875 (Posted: Mar 30, 2021 9AM)

More than 300 Food and Drug Administration-approved medications contain pharmacogenomic information in their labeling. Genetic variability may alter the therapeutic effects of commonly prescribed pain medications. Pharmacogenomic-guided therapy continues to gain traction in clinical practice, but a multitude of barriers to widespread pharmacogenomic implementation exist.

How pharmacogenomics enables precision approach to care
L Strazewski, AMA, March 2021 (Posted: Mar 25, 2021 8AM)

"What we learned is that almost everyone has at least one high-risk variant” that can affect response to medication, he said “About 20% of prescriptions in primary care fall into that category. About 50% of patients said they were more likely to take their medications, knowing that this information was being incorporated.”

Pharmacogenetic-guided glimepiride therapy in type-2 diabetes mellitus: a cost-effectiveness study
C Fokoun et al, PGX Journal, March 17, 2021 (Posted: Mar 19, 2021 8AM)

With pharmacogenetic-guided therapy, the cost to avoid an episode of severe hypoglycemia event per 100 000 patients treated was €421 834. Genotyping cost was the most influential factor on the incremental cost-effectiveness ratio. In conclusion, the potential cost of CYP2C9 genotype-guided dosing for glimepiride therapy is relatively high, and associated with modest improvements with respect to the number of hypoglycemia avoided, as compared with standard dosing.

CYP2D6 genotype and reduced codeine analgesic effect in real-world clinical practice
DC Leon et al, Pharmacogenomics Journal, March 2021 (Posted: Mar 15, 2021 4PM)

We studied 157 patients on codeine. Based on CYP2D6 genotyping, 69 were classified as poor/intermediate and 88 as normal/ultrarapid CYP2D6 metabolizers. In a propensity-score adjusted model, poor/intermediate metabolizers had lower odds (OR?=?0.35, p?=?0.02) of achieving a pain response than normal/ultrarapid metabolizers. Using a score that includes CYP2D6 phenotype and clinical variables, we found that response rate was 38.5% among patients in the high, 17.3% in the intermediate, and 9.4% in the low-score groups, respectively (p?=?0.001).

Pharmacogenomics guided versus standard antidepressant treatment in a community pharmacy setting: A randomized controlled trial.
Papastergiou John et al. Clinical and translational science 2021 (Posted: Mar 05, 2021 9AM)

In this prospective, single-blind randomized controlled design, we evaluated the impact of pharmacogenomics guided versus standard antidepressant treatment of depression and anxiety, implemented in three large community pharmacies. Participants were 213 outpatients diagnosed with major depressive disorder and/or generalized anxiety disorder, randomized to receive pharmacogenomics guided (n = 105) or standard antidepressant treatment (n = 108).

The Role of Pharmacogenomics in Contemporary Cardiovascular Therapy: A position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.
Magavern E F et al. European heart journal. Cardiovascular pharmacotherapy 2021 (Posted: Mar 02, 2021 9AM)

There is a strong and ever-growing body of evidence regarding the use of pharmacogenomics to inform cardiovascular pharmacology. However, there is no common position taken by international cardiovascular societies to unite diverse availability, interpretation and application of such data, nor is there recognition of the challenges of variation in clinical practice between countries.

Antihypertensive treatment guided by genetics: PEARL-HT, the randomized proof-of-concept trial comparing rostafuroxin with losartan
L Citterio et al, The Pharmacogenomics Journal, March 1, 2021 (Posted: Mar 02, 2021 8AM)

Clinical Utility of Pharmacogenomic Data Collected by a Health-System Biobank to Predict and Prevent Adverse Drug Events.
Shah Sonam N et al. Drug safety 2021 (Posted: Feb 26, 2021 11AM)

Medication-related harm represents a significant issue for patient safety and quality of care. One strategy to avoid preventable adverse drug events is to utilize patient-specific factors such as pharmacogenomics (PGx) to individualize therapy. We measured the number of patients enrolled in a health-system biobank with actionable PGx results who received relevant medications and assessed the incidence of adverse drug events (ADEs) that might have been prevented had the PGx results been used to inform prescribing.

Expanding evidence leads to new pharmacogenomics payer coverage
PE Empey et al, Genetics in Medicine, February 24, 2021 (Posted: Feb 25, 2021 7AM)

The cost of pharmacogenomic testing can be as low as a few hundred dollars and is often cost-effective.2 However, reimbursement has lagged as payers seek to understand variable test offerings, clinical utility, and economics. Few tests are reliably covered and payers have been critical of the multigene testing panels commonly offered by laboratories. Importantly, the US payer landscape for pharmacogenomic test reimbursement is improving.

A systematic review and meta-analysis of genotype-based and individualized data analysis of SLCO1B1 gene and statin-induced myopathy.
Turongkaravee Saowalak et al. The pharmacogenomics journal 2021 Feb (Posted: Feb 22, 2021 7AM)

This meta-analysis was conducted to determine the genotypic effects of rs4149056 and rs2306283 polymorphism in SLCO1B1 gene on myopathy in patients with statin use. Six studies were pooled. Genotypic effects of rs4149056 polymorphism in Caucasians indicated that statin users who carried CC and TC genotypes had a significantly higher risk of myopathy than those who carried TT genotype, with a pooled odds ratio (OR) of 2.9 and 1.6, respectively.

Rates of genetic testing in patients prescribed drugs with pharmacogenomic information in FDA-approved labeling.
Young John et al. The pharmacogenomics journal 2021 Feb (Posted: Feb 19, 2021 10AM)

This study examined rates of genetic testing in two cohorts of publicly insured individuals who have newly prescribed medication with FDA pharmacogenomic labeling guidance. Genetic testing was rare (4.4% and 10.5% in Medicaid and Medicare cohorts, respectively) Factors that emerged as predictors of the likelihood of undergoing genetic testing included White ethnicity (vs. Black), female gender, and age.

Mapping of susceptible variants for cold medicine-related Stevens–Johnson syndrome by whole-genome resequencing
Y Kawai et al, NPJ Genomic Medicine, February 2021 (Posted: Feb 15, 2021 8AM)

WGS was performed on samples from 133 patients with CM-SJS/TEN with SOC and 418 healthy controls to obtain single nucleotide polymorphisms (SNPs) and SVs. Genome-wide association tests were performed with these variants. Our genome-wide association test reproduced the associations of the common variants of HLA-A and loci on chromosome 16q12.1. We also identified novel associations of SVs on these loci and an aggregation of rare coding variants on the TPRM8 gene.

Race and Pharmacogenomics—Personalized Medicine or Misguided Practice?
CW Goodman et al, JAMA< January 25, 2021 (Posted: Jan 25, 2021 11AM)

Pharmacogenomics poses challenges for researchers, policy makers, and clinicians. Universal screening for genetic predisposition to adverse drug reactions would make race-based algorithms unnecessary, but imperatives to use limited resources judiciously may warrant more selective screening, targeted to high-prevalence groups, if such groups can be identified accurately.

Based on genes, nearly everyone is likely to have an atypical response to at least one drug
H Armitage, Stanford Medicine Blog, January 4, 2021 (Posted: Jan 05, 2021 8AM)

New data shows that almost everyone is likely to have an abnormal or "atypical" response to at least one therapeutic drug. The research found that nearly a quarter of the study's participants had been prescribed a drug for which they were predicted to have an atypical response. On average, participants were predicted to have an atypical response to 10 drugs.


Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.