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Rheumatoid Arthritis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Brent A. Luedders, Ted R. Mikuls, James R. O’Dell, Bryant R. England
Insights from the human genome project inspired the precision medicine approach. In RA, a better understanding of the human genome and how it interacts with medications could allow us to tailor therapies. This is already being utilized in a minority of RA patients who may be treated with azathioprine. Deficiency of the enzyme thiopurine S-methyltransferase (TPMT), which is responsible for metabolism of azathioprine, is associated with an increased risk for hematologic toxicity from azathioprine,114 and in patients with known deficient activity, there have been recommendations to either choose alternative agents or start at a reduced dose.115 Broader precision medicine RA treatment through pharmacogenomics may be on the horizon. A systematic review and meta-analysis identified more than twenty-five single nucleotide polymorphisms (SNPs) corresponding to genes involved in T cell function, NFκB, and TNF signaling that were predictive of response to anti-TNF treatment.116 These and additional SNPs may also be leveraged to predict response to other existing and yet-to-be-developed DMARDs. While currently focused on selecting the best therapy, pharmacogenomics also provides the opportunity to inform providers and patients on the selection of the optimal medication dose as well as the risks of adverse effects.
Genomic technologies
Published in Wendy A. Rogers, Jackie Leach Scully, Stacy M. Carter, Vikki A. Entwistle, Catherine Mills, The Routledge Handbook of Feminist Bioethics, 2022
Through all stages of life, genome testing can be used in the clinical setting to determine the presence of rare and complex disease risks and predispositions and for diagnostic purposes (Horton and Lucassen 2019; Shendure, Findlay and Snyder 2019). It is also employed for disease prognosis, and increasingly is being used in the selection and prioritization of certain therapeutic options over others. This new clinical area, pharmacogenomics, studies how people’s genomic variations affect their response to medications (Carr, Turner and Pirmohamed 2021). Physicians usually prescribe drugs based mostly on factors such as a patient’s age, sex, weight, and liver and kidney function. However, evidence suggests that genomic variations can affect how effective a drug can be or what side effects it might have. Pharmacogenomics screening can thus be used to increase the efficacy and safety of current and future drug treatments by identifying genetic variations that influence drug metabolism.
The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The technologies discussed above should bring many forms of personalized medicine into clinical practice in the future, although views on the likely timelines vary. The design, development, and marketing of pharmacogenomic tests are complex, and require a coordinated effort between a number of disciplines including medicine, the bioanalytical sciences and the clinical laboratory. New generations of health care specialists with appropriate knowledge and training will be required to interpret pharmacogenomic data, particularly where it can help guide drug choice, dosing, and likely side effects.
Current pharmacogenomic recommendations in chronic respiratory diseases: Is there a biomarker ready for clinical implementation?
Published in Expert Review of Respiratory Medicine, 2022
Ingrid Fricke-Galindo, Ramcés Falfán-Valencia
The pharmacogenomics of chronic respiratory diseases faces the same barriers as other areas of pharmacogenomics. Though not for pulmonary drugs, well-established biomarkers are available for their implementation in the clinical practice of chronic respiratory diseases. For instance, warfarin is one of the most consolidated biomarkers in pharmacogenomics. Nevertheless, the use of warfarin in pulmonary hypertension remains controversial [57,61,62], as well as the genotype-guided dosing of warfarin [58] due to the influence of the ethnic origin on the relation of genetic variants with the anticoagulant effects. Thus, for warfarin and different drugs, the impact of ethnicity on the benefit of individualizing therapy based on genetic tests must be assessed, mainly for the most important drugs in underrepresented populations in pharmacogenomic studies [58,63,64].
Risk of major adverse cardiovascular events of CYP2C19 loss-of-function genotype guided prasugrel/ticagrelor vs clopidogrel therapy for acute coronary syndrome patients undergoing percutaneous coronary intervention: a meta-analysis
Published in Platelets, 2021
Mohitosh Biswas, Most. Sumaiya Khatun Kali, Tapash Kumar Biswas, Baharudin Ibrahim
Precision medicine is the considerations of genetic characteristics and other intervening factors (e.g. life style, environment, etc.) in a subgroup of patients for optimizing safety and efficacy of medications [1,2]. One facet of this newly evolving arena is to take into account pharmacogenomics which is intended to tailor of treatments by considering individual genetic make-up. It has been replicated in numerous studies that carriers of CYP2C19 loss-of-function (LoF) alleles with acute coronary syndrome (ACS) patients especially those undergoing percutaneous coronary intervention (PCI) treating with clopidogrel are associated with increased risk of primary efficacy endpoint, e.g. major adverse cardiovascular events (MACEs) as well as secondary endpoints, e.g. cardiovascular (CV) death, myocardial infarction (MI), stroke, and stent thrombosis [3–6]. The findings of these studies suggest that CYP2C19 genotype guided antiplatelets therapy may improve patients’ clinical outcomes, that means patients carrying either one or two copies of CYP2C19 LoF alleles (CYP2C19*2,*3,*4,*5,*6,*8) need to be treated with alternative P2Y12 receptor blockers such as prasugrel or ticagrelor in order to reduce CYP2C19 LoF related primary and secondary adverse clinical outcomes. This recommendation is also highly supported by the clinical pharmacogenetics implementation consortium (CPIC) pharmacogenomics-based doing guideline of clopidogrel [7].
Compounding for women’s health: a compounder’s perspective – need, regulations, and future
Published in Climacteric, 2021
In the emerging field of pharmacogenomics, one strength does not fit all. Pharmacogenomics is the study of how genes affect a person’s response to drugs. This relatively new field combines pharmacology and genomics to develop effective, safe medications and doses that will be tailored to a person’s genetic make-up. An area of research includes breast cancer susceptibility using pharmacogenomic predictors, genes that are involved in the metabolism of sex hormones which underscore the potential cancer risk in menopausal patients receiving HRT, thus leading to genotype-guided safer HRT use66. In addition, pharmacogenetics in pregnancy has potential application in several areas of obstetric therapeutics including opioid pain management, antihypertensive therapy, antidepressant medications, pre-term labor tocolytics, antenatal corticosteroids, and anti-emetics67.