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Clinical Pharmacology and Therapeutics Aug 2020Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used analgesics due to their lack of addictive potential. However, NSAIDs have the potential to... (Meta-Analysis)
Meta-Analysis
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used analgesics due to their lack of addictive potential. However, NSAIDs have the potential to cause serious gastrointestinal, renal, and cardiovascular adverse events. CYP2C9 polymorphisms influence metabolism and clearance of several drugs in this class, thereby affecting drug exposure and potentially safety. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for NSAIDs based on CYP2C9 genotype (updates at www.cpicpgx.org).
Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Decision-Making; Consensus; Cytochrome P-450 CYP2C9; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomic Variants; Phenotype; Predictive Value of Tests; Risk Assessment; Risk Factors
PubMed: 32189324
DOI: 10.1002/cpt.1830 -
Journal of Cardiovascular Pharmacology... May 2020Clopidogrel is widely used after the percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and requires activation by cytochrome P450...
Economic Evaluations of CYP2C19 Genotype-Guided Antiplatelet Therapy Compared to the Universal Use of Antiplatelets in Patients With Acute Coronary Syndrome: A Systematic Review.
BACKGROUND AND OBJECTIVES
Clopidogrel is widely used after the percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and requires activation by cytochrome P450 (CYP), primarily CYP2C19. Patients with CYP2C19 loss-of-function alleles are at increased risk of major adverse cardiovascular events, while more expensive novel antiplatelet agents (ticagrelor and prasugrel) are unaffected by the CYP2C19 mutations. This systematic review aims to answer the question about whether overall evidence supports the genotype-guided selection of antiplatelet therapy as a cost-effective strategy in post-PCI ACS.
METHODS
A systematic literature search of PubMed, EMBASE, EconLit, and PharmGKB was done to identify all the economic evaluations related to genotype-guided therapy compared to the universal use of antiplatelets in ACS patients. Quality of Health Economic Studies tool was used for quality assessment.
RESULTS
The search identified 13 articles, where genotype-guided treatment was compared to universal clopidogrel, ticagrelor, and/or prasugrel. Six studies showed that genotype-guided therapy was cost-effective compared to universal clopidogrel, while 5 studies showed that it was dominant. One study specified that genotype-guided with ticagrelor is cost-effective only in both CYP2C19 intermediate and poor metabolizers. Genotype-guided therapy was dominant when compared to universal prasugrel, ticagrelor, or both in 5, 1, and 3 studies, respectively. Only 2 studies reported that universal ticagrelor was cost-effective compared to genotype-guided treatment. All the included articles had good quality.
CONCLUSION
Based on current economic evaluations in the literature, implementing CYP2C19 genotype-guided therapy is a cost-effective approach in guiding the selection of medication in patients with ACS undergoing PCI.
Topics: Acute Coronary Syndrome; Clinical Decision-Making; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Costs; Humans; Patient Selection; Pharmacogenomic Testing; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Precision Medicine; Predictive Value of Tests; Ticagrelor; Treatment Outcome
PubMed: 32027168
DOI: 10.1177/1074248420902298 -
Value in Health : the Journal of the... Jan 2020Monoclonal antibodies against epidermal growth factor receptor (EGFR) have proved beneficial for the treatment of metastatic colorectal cancer (mCRC), particularly when...
BACKGROUND
Monoclonal antibodies against epidermal growth factor receptor (EGFR) have proved beneficial for the treatment of metastatic colorectal cancer (mCRC), particularly when combined with predictive biomarkers of response. International guidelines recommend anti-EGFR therapy only for RAS (NRAS,KRAS) wild-type tumors because tumors with RAS mutations are unlikely to benefit.
OBJECTIVES
We aimed to review the cost-effectiveness of RAS testing in mCRC patients before anti-EGFR therapy and to assess how well economic evaluations adhere to guidelines.
METHODS
A systematic review of full economic evaluations comparing RAS testing with no testing was performed for articles published in English between 2000 and 2018. Study quality was assessed using the Quality of Health Economic Studies scale, and the British Medical Journal and the Philips checklists.
RESULTS
Six economic evaluations (2 cost-effectiveness analyses, 2 cost-utility analyses, and 2 combined cost-effectiveness and cost-utility analyses) were included. All studies were of good quality and adopted the perspective of the healthcare system/payer; accordingly, only direct medical costs were considered. Four studies presented testing strategies with a favorable incremental cost-effectiveness ratio under the National Institute for Clinical Excellence (£20 000-£30 000/QALY) and the US ($50 000-$100 000/QALY) thresholds.
CONCLUSIONS
Testing mCRC patients for RAS status and administering EGFR inhibitors only to patients with RAS wild-type tumors is a more cost-effective strategy than treating all patients without testing. The treatment of mCRC is becoming more personalized, which is essential to avoid inappropriate therapy and unnecessarily high healthcare costs. Future economic assessments should take into account other parameters that reflect the real world (eg, NRAS mutation analysis, toxicity of biological agents, genetic test sensitivity and specificity).
Topics: Antineoplastic Agents, Immunological; Clinical Decision-Making; Colorectal Neoplasms; Cost-Benefit Analysis; DNA Mutational Analysis; Drug Costs; ErbB Receptors; Genes, ras; Genetic Predisposition to Disease; Health Care Costs; Humans; Mutation; Neoplasm Metastasis; Patient Selection; Pharmacogenomic Testing; Pharmacogenomic Variants; Phenotype; Precision Medicine; Predictive Value of Tests; Quality-Adjusted Life Years
PubMed: 31952666
DOI: 10.1016/j.jval.2019.07.009 -
The Pharmacogenomics Journal Oct 2020A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in...
A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in Childhood Asthma (PiCA) consortia members was conducted. Studies were eligible if genetic polymorphisms were compared with suspected ADR(s) in a patient with asthma, as either a primary or secondary outcome. Five studies met the inclusion criteria. The ADRs and polymorphisms identified were change in lung function tests (rs1042713), adrenal suppression (rs591118), and decreased bone mineral density (rs6461639) and accretion (rs9896933, rs2074439). Two of these polymorphisms were replicated within the paper, but none had external replication. Priorities from PiCA consortia members (representing 15 institution in eight countries) for future studies were tachycardia (SABA/LABA), adrenal suppression/crisis and growth suppression (corticosteroids), sleep/behaviour disturbances (leukotriene receptor antagonists), and nausea and vomiting (theophylline). Future pharmacogenomic studies in asthma should collect relevant ADR data as well as markers of efficacy.
Topics: Adolescent; Adult; Anti-Asthmatic Agents; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Pharmacogenomic Testing; Pharmacogenomic Variants; Phenotype; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; Young Adult
PubMed: 31949291
DOI: 10.1038/s41397-019-0140-y -
Genetics in Medicine : Official Journal... Mar 2020To examine the evidence on the cost-effectiveness of implementing pharmacogenomics (PGx) in cardiovascular disease (CVD) care.
PURPOSE
To examine the evidence on the cost-effectiveness of implementing pharmacogenomics (PGx) in cardiovascular disease (CVD) care.
METHODS
We conducted a systematic review using multiple databases from inception to 2018. The titles and abstracts of cost-effectiveness studies on PGx-guided treatment in CVD care were screened, and full texts were extracted.
RESULTS
We screened 909 studies and included 46 to synthesize. Acute coronary syndrome and atrial fibrillation were the predominantly studied conditions (59%). Most studies (78%) examined warfarin-CYP2C9/VKORC1 or clopidogrel-CYP2C19. A payer's perspective was commonly used (39%) for cost calculations, and most studies (46%) were US-based. The majority (67%) of the studies found PGx testing to be cost-effective in CVD care, but cost-effectiveness varied across drugs and conditions. Two studies examined PGx panel testing, of which one examined pre-emptive testing strategies.
CONCLUSION
We found mixed evidence on the cost-effectiveness of PGx in CVD care. Supportive evidence exists for clopidogrel-CYP2C19 and warfarin-CYP2C9/VKORC1, but evidence is limited in other drug-gene combinations. Gaps persist, including unclear explanation of perspective and cost inputs, underreporting of study design elements critical to economic evaluations, and limited examination of PGx panel and pre-emptive testing for their cost-effectiveness. This review identifies the need for further research on economic evaluations of PGx implementation.
Topics: Cardiovascular Diseases; Clopidogrel; Cost-Benefit Analysis; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Humans; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; Vitamin K Epoxide Reductases; Warfarin
PubMed: 31591509
DOI: 10.1038/s41436-019-0667-y -
Medicine Aug 2019Over the past 10 years, epilepsy genetics has made dramatic progress. This study aimed to analyze the knowledge structure and the advancement of epilepsy genetics over... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Over the past 10 years, epilepsy genetics has made dramatic progress. This study aimed to analyze the knowledge structure and the advancement of epilepsy genetics over the past decade based on co-word analysis of medical subject headings (MeSH) terms.
METHODS
Scientific publications focusing on epilepsy genetics from the PubMed database (January 2009-December 2018) were retrieved. Bibliometric information was analyzed quantitatively using Bibliographic Item Co-Occurrence Matrix Builder (BICOMB) software. A knowledge social network analysis and publication trend based on the high-frequency MeSH terms was built using VOSviewer.
RESULTS
According to the search strategy, a total of 5185 papers were included. Among all the extracted MeSH terms, 86 high-frequency MeSH terms were identified. Hot spots were clustered into 5 categories including: "ion channel diseases," "beyond ion channel diseases," "experimental research & epigenetics," "single nucleotide polymorphism & pharmacogenetics," and "genetic techniques". "Epilepsy," "mutation," and "seizures," were located at the center of the knowledge network. "Ion channel diseases" are typically in the most prominent position of epilepsy genetics research. "Beyond ion channel diseases" and "genetic techniques," however, have gradually grown into research cores and trends, such as "intellectual disability," "infantile spasms," "phenotype," "exome," " deoxyribonucleic acid (DNA) copy number variations," and "application of next-generation sequencing." While ion channel genes such as "SCN1A," "KCNQ2," "SCN2A," "SCN8A" accounted for nearly half of epilepsy genes in MeSH terms, a number of additional beyond ion channel genes like "CDKL5," "STXBP1," "PCDH19," "PRRT2," "LGI1," "ALDH7A1," "MECP2," "EPM2A," "ARX," "SLC2A1," and more were becoming increasingly popular. In contrast, gene therapies, treatment outcome, and genotype-phenotype correlations were still in their early stages of research.
CONCLUSION
This co-word analysis provides an overview of epilepsy genetics research over the past decade. The 5 research categories display publication hot spots and trends in epilepsy genetics research which could consequently supply some direction for geneticists and epileptologists when launching new projects.
Topics: Bibliometrics; Epigenomics; Epilepsy; Humans; Ion Channels; Medical Subject Headings; Mutation; Pharmacogenomic Testing; Phenotype; Seizures
PubMed: 31393404
DOI: 10.1097/MD.0000000000016782 -
Seminars in Oncology Jun 2019Use of precision medicine in oncology is burgeoning and can provide patients with new treatment options. However, it is not clear how precision medicine is impacting... (Review)
Review
Use of precision medicine in oncology is burgeoning and can provide patients with new treatment options. However, it is not clear how precision medicine is impacting healthcare professionals (HCPs), particularly with regards to their concerns about this new approach. We therefore synthesized the existing literature on HCPs' attitudes toward cancer precision medicine. We searched four databases for relevant articles. Two reviewers screened eligible articles and extracted data. We assessed the quality of each article using the QualSyst tool. We found 22 articles, representing 4,321 HCPs (63.7% cancer specialists). HCPs held largely positive attitudes toward cancer precision medicine, including their capacity to facilitate treatment decisions and provide prognostic information. However, they also had concerns regarding costs, insurance coverage, limited HCP knowledge about precision medicine, potential misuse, difficulties accessing the tests, and delays in receiving test results. Most HCPs felt that test-related decisions should be shared between families and HCPs. HCPs intended to disclose actionable results but were less inclined to disclose negative/secondary findings. HCPs had a strong preference for genetic counselor involvement when disclosing germline findings. Most HCPs intended to use somatic and germline tests in their future practice but the extent to which pharmacogenomic tests will be used is uncertain. HCPs indicated that additional evidence supporting test utility and increased availability of treatment guidelines could facilitate the use of testing. HCPs held generally positive attitudes toward cancer precision medicine, however there were some key concerns. Addressing concerns early, devising educational support for HCPs and developing guidelines may facilitate the successful implementation of precision medicine trials in the future.
Topics: Attitude of Health Personnel; Germ-Line Mutation; Humans; Neoplasms; Precision Medicine; Prognosis
PubMed: 31221444
DOI: 10.1053/j.seminoncol.2019.05.001 -
Clinical Pharmacology and Therapeutics Oct 2019The HIV type-1 nonnucleoside reverse transcriptase inhibitor, efavirenz, is widely used to treat HIV type-1 infection. Efavirenz is predominantly metabolized into...
The HIV type-1 nonnucleoside reverse transcriptase inhibitor, efavirenz, is widely used to treat HIV type-1 infection. Efavirenz is predominantly metabolized into inactive metabolites by cytochrome P450 (CYP)2B6, and patients with certain CYP2B6 genetic variants may be at increased risk for adverse effects, particularly central nervous system toxicity and treatment discontinuation. We summarize the evidence from the literature and provide therapeutic recommendations for efavirenz prescribing based on CYP2B6 genotypes.
Topics: Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Cytochrome P-450 CYP2B6; HIV Infections; HIV-1; Humans; Pharmacogenetics; Pharmacogenomic Testing; Practice Guidelines as Topic
PubMed: 31006110
DOI: 10.1002/cpt.1477 -
Journal of Managed Care & Specialty... Feb 2019Pharmacogenetic testing can provide predictive insights about the efficacy and safety of drugs used in cancer treatment. Although many drug-gene associations have been...
BACKGROUND
Pharmacogenetic testing can provide predictive insights about the efficacy and safety of drugs used in cancer treatment. Although many drug-gene associations have been reported in the literature, the strength of evidence supporting each association can vary significantly. Even among the subgroup of drugs classified by the PharmGKB database to have a high or moderate level of evidence, there is limited information regarding the economic value of pharmacogenetic testing.
OBJECTIVES
To: (a) summarize the available pharmacoeconomic evidence assessing the value of pharmacogenetic testing for cancer drugs with clinically relevant drug-gene associations; (b) determine the quality of the studies that contain this evidence; and (c) discuss the quality of this evidence with respect to the level of evidence of the drug-gene associations.
METHODS
The PharmGKB database was used to identify cancer drugs with clinically relevant drug-gene associations graded high (1A, 1B) or moderate (2A, 2B). A systematic literature review was conducted using these drugs. Ovid MEDLINE and Embase databases were searched to identify cost-effectiveness, cost-utility, or cost-minimization studies comparing pharmacogenetic testing to an alternative. Cost and effect values from every relevant comparison within the studies were extracted, and the incremental cost-effectiveness ratio (ICER) was either extracted or calculated for each comparison. Quality assessment was conducted for each study using the Quality of Health Economic Studies (QHES) instrument. Qualitative synthesis was used to summarize the data.
RESULTS
The search yielded 2,191 citations, of which 35 studies met the inclusion criteria. Pharmacoeconomic studies were available for the following drugs from the PharmGKB database: fluoropyrimidine, 6-mercaptopurine, irinotecan, carboplatin, cisplatin, erlotinib, gefitinib, cetuximab, panitumumab, and trastuzumab. The studies were conducted in Asia, Europe, Canada, the United States, and Mexico and reported cost-utility, cost-effectiveness, and cost-minimization outcomes. The mean QHES score was 80 (SD = 22) for the studies of drug-gene pairs with high (1A, 1B) and moderate (2A, 2B) levels of evidence (1A = 82, 1B = 93, 2A = 71, and 2B = 74). There was variation across studies in terms of reporting. 109 relevant comparisons were identified within the studies. Of those that reported cost per life-year or cost per quality-adjusted life-year (n = 58 comparisons), pharmacogenetic testing was dominant in 21% overall and 42%, 21%, 17%, and 5% of the comparisons in Asia, Europe, Canada, and the United States, respectively. Variability was observed in the ICER values regardless of geographic region or drug. Pharmacogenetic testing was cost saving in 17 of 19 cost-minimization comparisons and was favored most frequently when compared with genetically indiscriminate strategies containing the drug of interest.
CONCLUSIONS
There was mixed evidence regarding the value of pharmacogenetic testing to guide cancer treatment. For future pharmacogenomic-related economic studies, we recommend prioritizing clinically relevant drug-gene associations and greater adherence to available best practice guidelines for conducting and reporting economic evaluation studies.
DISCLOSURES
No outside funding supported this review. Part of Hussain's research time was supported by a Merit Review Award (I01 BX000545), Medical Research Service, U.S. Department of Veterans Affairs. Hussain also reports personal fees from Bristol-Myers Squibb, AstraZeneca, Novartis, Bayer HealthCare Pharmaceuticals, and France Foundation, outside the submitted work. Onukwugha reports grants from Pfizer and Bayer HealthCare Pharmaceuticals, along with advisory board fees from Novo Nordisk, outside the submitted work. Faruque, Neuberger, and Noh have nothing to disclose.
Topics: Antineoplastic Agents; Cost-Benefit Analysis; Economics, Pharmaceutical; Humans; Neoplasms; Pharmacogenomic Testing; Quality-Adjusted Life Years
PubMed: 30698084
DOI: 10.18553/jmcp.2019.25.2.260 -
Catheterization and Cardiovascular... Aug 2019This study aimed to evaluate the efficacy and safety of genotype- and phenotype-guided intensified antiplatelet therapy compared with conventional therapy in patients... (Meta-Analysis)
Meta-Analysis
Personalized antiplatelet therapy in patients with coronary artery disease undergoing percutaneous coronary intervention: A network meta-analysis of randomized clinical trials.
OBJECTIVES
This study aimed to evaluate the efficacy and safety of genotype- and phenotype-guided intensified antiplatelet therapy compared with conventional therapy in patients undergoing stent implantation.
BACKGROUND
Although potent P2Y receptor inhibitors are recommended for percutaneous coronary intervention (PCI)-treated acute coronary syndrome, their usage is limited by a high bleeding risk. Therefore, personalized antiplatelet therapy could provide a valuable foundation for selection of antiplatelet therapy in this population.
METHODS
We conducted a Bayesian network meta-analysis for all randomized clinical trials (RCTs) that evaluated genotype- and/or phenotype-guided therapy in PCI-treated coronary artery disease.
RESULTS
Thirteen RCTs were included with a total of 6,845 patients. The results showed no significant differences in major adverse cardiovascular events (MACE) between the treatment options ((genotype guided vs. standard of care; OR 0.64; 95% CI: 0.38-1.05) and (phenotype vs. standard of care; OR 0.93; 95% CI: 0.54-1.37)). In addition, no significant differences were demonstrated in bleeding events ((genotype guided vs. standard of care; OR 0.73; 95% CI: 0.45-1.25) and (phenotype vs. standard of care; OR 0.90; 95% CI: 0.62-1.39)).
CONCLUSIONS
In this mixed treatment meta-analysis of RCTs, neither genotype- nor phenotype-guided antiplatelet therapy in patients with PCI-treated coronary artery disease was superior to conventional therapy.
Topics: Bayes Theorem; Clinical Decision-Making; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Hemorrhage; Humans; Network Meta-Analysis; Patient Selection; Percutaneous Coronary Intervention; Pharmacogenomic Testing; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Precision Medicine; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome
PubMed: 30628754
DOI: 10.1002/ccd.28075