UGT1A6- and UGT2B7-related valproic acid pharmacogenomics according to age groups and total drug concentration levels.

Pharmacogenomics. 2016 May 27;

Authors: Chatzistefanidis D, Lazaros L, Giaka K, Nakou I, Tzoufi M, Georgiou I, Kyritsis A, Markoula S

Abstract
AIM: The role of UGT1A6 and UGT2B7 polymorphisms and the impact of total drug plasma concentration in valproic acid (VPA) pharmacogenomics.
PATIENTS & METHODS: A total of 134 Greek patients were recruited (76 adults). Patients were genotyped for UGT1A6 19T>G, 541A>G and 552A>C and UGT2B7 802T>C polymorphisms. Patients' demographic and clinical data were registered. Natural logarithm of concentration-to-dose ratio (CDR) was also calculated as the final outcome.
RESULTS: No significant genotype-related differences in VPA metabolism were noted among various subgroups. An increased lnCDR ratio was noted in children patients compared with adults suggesting increased metabolic capability in younger ages.
CONCLUSION: UGT1A6 and UGT2B7 genotypes were not related to significant changes in VPA metabolism, even after controlling for total drug concentration levels. Younger ages were associated with increased VPA clearance rate.

PMID: 27232006 [PubMed - as supplied by publisher]

P2Y12-ADP receptor antagonists: Days of future and past.

World J Cardiol. 2016 May 26;8(5):327-32

Authors: Laine M, Paganelli F, Bonello L

Abstract
Antiplatelet therapy is the cornerstone of the therapeutic arsenal in coronary artery disease. Thanks to a better understanding in physiology, pharmacology and pharmacogenomics huge progress were made in the field of platelet reactivity inhibition thus allowing the expansion of percutaneous coronary intervention. Stent implantation requires the combination of two antiplatelet agents acting in a synergistic way. Asprin inhibit the cyclo-oxygenase pathway of platelet activation while clopidogrel is a P2Y12 adenosine diphosphate (ADP)-receptor antagonist. This dual antiplatelet therapy has dramatically improved the prognosis of stented patients. However, due to pharmacological limitations of clopidogrel (interindividual variability in its biological efficacy, slow onset of action, mild platelet reactivity inhibition) ischemic recurrences remained high following stent implantation especially in acute coronary syndrome patients. Thus, more potent P2Y12-ADP receptor inhibitors were developped including prasugrel, ticagrelor and more recently cangrelor to overcome these pitfalls. These new agents reduced the rate of thrombotic events in acute coronary syndrome patients at the cost of an increased bleeding risk. The abundance in antiplatelet agents allow us to tailor our strategy based on the thrombotic/bleeding profile of each patient. Recently, the ACCOAST trial cast a doubt on the benefit of pre treatment in non-ST segment elevation acute coronary syndrome. The aim of the present review is to summarize the results of the main studies dealing with antiplatelet therapy in stented/acute coronary syndromes patients.

PMID: 27231519 [PubMed]

Cytotoxicity of Salvia miltiorrhiza Against Multidrug-Resistant Cancer Cells.

Am J Chin Med. 2016 May 24;:1-24

Authors: Wu CF, Bohnert S, Thines E, Efferth T

Abstract
Salvia miltiorrhiza Bunge (Lamiaceae) is a well-known Chinese herb that possesses numerous therapeutic activities, including anticancer effects. In this study, the cytotoxicity and the biological mechanisms of S. miltiorrhiza (SM) root extract on diverse resistant and sensitive cancer cell lines were investigated. CEM/ADR5000 cells were 1.68-fold resistant to CCRF-CEM cells, while HCT116 (p53[Formula: see text] and U87.MG[Formula: see text]EGFR cells were hypersensitive (collateral sensitive) compared to their parental cells. SM root extract stimulated ROS generation, cell cycle S phase arrest and apoptosis. The induction of the intrinsic apoptotic pathway was validated by increased cleavage of caspase 3, 7, 9 and poly ADP-ribose polymerase (PARP). MAP kinases including JNK, ERK1/2 and p38 were obviously phosphorylated and nuclear P65 was downregulated upon SM treatment. Transcriptome-wide COMPARE analysis revealed that the expression of encoding genes with diverse functions were associated with the cellular response to cryptotanshinone, one of the main constituents of SM root extract. In conclusion, SM root extract exerted profound cytotoxicity towards various sensitive and resistant cancer cells and induced the intrinsic apoptotic pathway.

PMID: 27222067 [PubMed - as supplied by publisher]

Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy.

Pharmacogenomics J. 2016 May 24;

Authors: Zur RM, Roy LM, Ito S, Beyene J, Carew C, Ungar WJ

Abstract
Thiopurine S-methyltransferase (TPMT) deficiency increases the risk of serious adverse events in persons receiving thiopurines. The objective was to synthesize reported sensitivity and specificity of TPMT phenotyping and genotyping using a latent class hierarchical summary receiver operating characteristic meta-analysis. In 27 studies, pooled sensitivity and specificity of phenotyping for deficient individuals was 75.9% (95% credible interval (CrI), 58.3-87.0%) and 98.9% (96.3-100%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 90.4% (79.1-99.4%) and 100.0% (99.9-100%), respectively. For individuals with deficient or intermediate activity, phenotype sensitivity and specificity was 91.3% (86.4-95.5%) and 92.6% (86.5-96.6%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 88.9% (81.6-97.5%) and 99.2% (98.4-99.9%), respectively. Genotyping has higher sensitivity as long as TPMT*2 and TPMT*3 are tested. Both approaches display high specificity. Latent class meta-analysis is a useful method for synthesizing diagnostic test performance data for clinical practice guidelines.The Pharmacogenomics Journal advance online publication, 24 May 2016; doi:10.1038/tpj.2016.37.

PMID: 27217052 [PubMed - as supplied by publisher]

Clinical-pharmacogenetic predictive models for MTX discontinuation due to adverse events in rheumatoid arthritis.

Pharmacogenomics J. 2016 May 24;

Authors: Jenko B, Lusa L, Tomsic M, Praprotnik S, Dolzan V

Abstract
We describe a novel approach to investigate and evaluate combined effect of a large number of clinical and pharmacogenetic factors on treatment outcome. We have used this approach to investigate predictors of methotrexate (MTX)-induced adverse events (AEs) leading to treatment discontinuation in rheumatoid arthritis (RA) patients. In total, 333 RA patients were genotyped for 34 polymorphisms in MTX transporters, folate and adenosine pathways. The effect of clinical and pharmacogenetic factors was assessed with penalized regression in the cause-specific Cox proportional hazards model. The predictive capacity was evaluated with the area under time-dependent receiver operating characteristic curve where cross-validation was applied. SLC19A1, ABCG2, ADORA3 and TYMS were associated with discontinuation because of AEs in clinical-pharmacogenetic model. Cross-validation showed that both clinical-pharmacogenetic model and nongenetic model had worthless predictive ability for MTX discontinuation because of AEs. These models could be further improved, either with additional polymorphisms or with epigenetic predictors.The Pharmacogenomics Journal advance online publication, 24 May 2016; doi:10.1038/tpj.2016.36.

PMID: 27217051 [PubMed - as supplied by publisher]

Implementing Pharmacogenomics at Your Institution: Establishment and Overcoming Implementation Challenges.

Clin Transl Sci. 2016 May 23;

Authors: Arwood MJ, Chumnumwat S, Cavallari LH, Nutescu EA, Duarte JD

Abstract
With advancements in pharmacogenomics research and genotyping technology, implementation of pharmacogenomics into clinical practice is now feasible. The aim of this publication is to serve as a tutorial for institutions interested in developing pharmacogenomics services. Topics covered include resources needed, clinical decision support establishment, choosing a genotyping platform, and challenges faced with pharmacogenomics service implementation. This tutorial provides practical advice, drawing upon experience of two established clinical pharmacogenomics services. This article is protected by copyright. All rights reserved.

PMID: 27214750 [PubMed - as supplied by publisher]

Exome Sequencing of Extreme Clopidogrel Response Phenotypes Identifies B4GALT2 as a Determinant of On-treatment Platelet Reactivity.

Clin Pharmacol Ther. 2016 May 23;

Authors: Scott SA, Collet JP, Baber U, Yang Y, Peter I, Linderman M, Sload J, Qiao W, Kini AS, Sharma SK, Desnick RJ, Fuster V, Hajjar RJ, Montalescot G, Hulot JS

Abstract
Interindividual variability in platelet aggregation is common among patients treated with clopidogrel, and both high and low (LTPR) on-treatment platelet reactivity increase risks for adverse clinical outcomes. CYP2C19 influences clopidogrel response but only accounts for ∼12% of the variability in platelet reactivity. To identify novel variants implicated in on-treatment platelet reactivity, coronary artery disease (CAD) patients with extreme pharmacodynamic responses to clopidogrel and wild-type CYP2C19 were subjected to exome sequencing. Candidate variants that clustered in the LTPR subgroup subsequently were genotyped across the discovery cohort (n=636). Importantly, carriers of B4GALT2 c.909C>T had lower on-treatment P2Y12 reaction units (PRU; p=0.0077) and residual platelet aggregation (p=0.0008) compared to non-carriers, which remained significant after adjusting for CYP2C19 and other clinical variables in both the discovery (p=0.0298) and replication (n=160; PRU: p=0.0001) cohorts. B4GALT2 is a platelet-expressed galactosyltransferase, indicating that B4GALT2 c.909C>T may influence clopidogrel sensitivity through atypical cell-surface glycoprotein processing and platelet adhesion. This article is protected by copyright. All rights reserved.

PMID: 27213804 [PubMed - as supplied by publisher]

Adenosine Hypothesis of Antipsychotic Drugs Revisited: Pharmacogenomics Variation in Nonacute Schizophrenia.

OMICS. 2016 May;20(5):283-289

Authors: Turčin A, Dolžan V, Porcelli S, Serretti A, Plesničar BK

Abstract
The existing antipsychotic therapy is based on dopamine hyperfunction and glutamate hypofunction hypotheses of schizophrenia. Adenosine receptors (ADORA) have a neuromodulatory role and can control dopaminergic and glutamatergic systems. To elucidate the effect of ADORA polymorphisms on psychopathological symptoms and adverse effects in patients with schizophrenia on long-term antipsychotic treatment, we examined 127 nonacute schizophrenia outpatients in a cross-sectional study using the Positive and Negative Symptoms Scale, Simpson-Angus Scale, Barnes Akathisia Rating Scale, and Abnormal Involuntary Movement Scale. All patients were genotyped for 18 polymorphisms in ADORA1, ADORA2A, and ADORA3. We found an association between ADORA1 rs3766566 and psychopathological symptoms (p = 0.006), in particular, with positive psychopathological symptoms (p = 0.010) and general psychopathological symptoms (p = 0.023), between ADORA2A rs2298383 and general psychopathological symptoms (p = 0.046), and between ADORA2A rs5751876 and akathisia (p = 0.015). Haplotype analysis showed an association between ADORA1 CTCAACG haplotype and overall psychopathological symptoms (p = 0.019), positive psychopathological symptoms (p = 0.021), and akathisia (p = 0.028). ADORA2A TCCTC haplotype was associated with parkinsonism (p = 0.014). ADORA3 CACTAC was associated with akathisia (p = 0.042), whereas CACTAT was associated with akathisia (p = 0.045) and tardive dyskinesia (p = 0.023). The results of this first comprehensive study on ADORA polymorphisms in patients with nonacute schizophrenia receiving long-term antipsychotic therapy suggest an important neuromodulatory role of ADORA receptors in both psychopathological symptoms and adverse effects of antipsychotics.

PMID: 27195966 [PubMed - as supplied by publisher]

Genome-Wide Association Study of Absolute QRS Voltage Identifies Common Variants of TBX3 as Genetic Determinants of Left Ventricular Mass in a Healthy Japanese Population.

PLoS One. 2016;11(5):e0155550

Authors: Sano M, Kamitsuji S, Kamatani N, Tabara Y, Kawaguchi T, Matsuda F, Yamagishi H, Fukuda K, Japan Pharmacogenomics Data Science Consortium (JPDSC)

Abstract
Left ventricular hypertrophy (LVH) represents a common final pathway leading to heart failure. We have searched for genetic determinants of left ventricular (LV) mass using values for absolute electrocardiographic QRS voltage in a healthy Japanese population. After adjusting for covariates, the corrected S and R wave voltages in leads V1 and V5 from 2,994 healthy volunteers in the Japan Pharmacogenomics Data Science Consortium (JPDSC) database were subjected to a genome-wide association study. Potential associations were validated by an in silico replication study using an independent Japanese population obtained from the Nagahama Prospective Genome Cohort for Comprehensive Human Bioscience. We identified a novel association between the lead V5, R wave voltage in Japanese individuals and SNP rs7301743[G], which maps near the gene encoding T-box transcription factor Tbx3. Meta-analysis of two independent Japanese datasets demonstrated a marginally significant association of SNP rs7301743 in TBX3|MED13L with a 0.071 mV (95% CI, 0.038-0.11 mV) shorter R wave amplitude in the V5 lead per minor allele copy (P = 7.635 x 10-8). The transcriptional repressor, TBX3, is proposed to suppress the development of working ventricular myocardium. Our findings suggest that genetic variation of Tbx3 is associated with LV mass in a healthy Japanese population.

PMID: 27195777 [PubMed - as supplied by publisher]

Genotyping NUDT15 can predict the dose reduction of 6-MP for children with acute lymphoblastic leukemia especially at a preschool age.

J Hum Genet. 2016 May 19;

Authors: Suzuki H, Fukushima H, Suzuki R, Hosaka S, Yamaki Y, Kobayashi C, Sakai A, Imagawa K, Iwabuchi A, Yoshimi A, Nakao T, Kato K, Tsuchida M, Kiyokawa N, Koike K, Noguchi E, Fukushima T, Sumazaki R

Abstract
The pharmacokinetics among children has been altered dynamically. The difference between children and adults is caused by immaturity in things such as metabolic enzymes and transport proteins. The periods when these alterations happen vary from a few days to some years after birth. We hypothesized that the effect of gene polymorphisms associated with the dose of medicine could be influenced by age. In this study, we analyzed 51 patients with childhood acute lymphoblastic leukemia (ALL) retrospectively. We examined the associations between the polymorphism in NUDT15 and clinical data, especially the dose of 6-mercaptopurine (6-MP). Ten of the patients were heterozygous for the variant allele in NUDT15. In patients under 7 years old with NUDT15 variant allele, the average administered dose of 6-MP was lower than that for the patients homozygous for the wild-type allele (P=0.04). Genotyping of NUDT15 could be a beneficial to estimate the tolerated dose of 6-MP for patients with childhood ALL, especially at a preschool age in Japan. Furthermore, the analysis with stratification by age might be useful in pharmacogenomics among children.Journal of Human Genetics advance online publication, 19 May 2016; doi:10.1038/jhg.2016.55.

PMID: 27193222 [PubMed - as supplied by publisher]

Exploiting microRNA Specificity and Selectivity: Paving a Sustainable Path Towards Precision Medicine.

Adv Exp Med Biol. 2015;888:1-3

Authors: Santulli G

Abstract
In his State of the Union address before both chambers of the US Congress, President Barack Obama called for increased investment in US infrastructure and research and announced the launch of a new Precision Medicine Initiative, aiming to accelerate biomedical discovery. Due to their well-established selectivity and specificity, microRNAs can represent a useful tool, both in diagnosis and therapy, in forging the path towards the achievement of precision medicine. This introductory chapter represents a guide for the Reader in examining the functional roles of microRNAs in the most diverse aspects of clinical practice, which will be explored in this third volume of the microRNA trilogy.

PMID: 26663175 [PubMed - indexed for MEDLINE]

Editorial.

Cell Mol Biol (Noisy-le-grand). 2016;62(5):1

Authors: Farooqi AA

Abstract
To optimize treatment, we need to understand biology of different diseases in much more detail with emphasis on morphological, proteomic, genetic and epigenetic grounds. Keeping in view the facts and stimulating developments in molecular pathology, it is worthwhile to present an up-date on this topic.It is becoming progressively more understandable that exciting fields of pharmacogenomics and pharmacogenetics have revolutionized field of medicine. Better understanding of underlying mechanisms of different diseases has provided us with better ways to treat illnesses. There cannot be a distinct definition of 'discipline' of pathology, mainly because investigation of human disease encompasses all the scientific disciplines of biomedical research. Sen et al reported that hyperbarıc oxygen (HBO) administration affected the endocrinological functions of fat tissue. Observation of significant increases in leptin, visfatin and IL-10 levels, leads to the consideration that in near future HBO administration may be applied as treatment for obesity, DM, eating disorders and obesity related diseases...

PMID: 27188861 [PubMed - as supplied by publisher]

Hepatotoxicity of targeted therapy for cancer.

Expert Opin Drug Metab Toxicol. 2016 May 17;

Authors: Lee KW, Chan SL

Abstract
Molecular targeted agents (MTA) have become the mainstay of treatment for many cancers in the past decade. Hepatotoxicity of varying forms and severity is common with the use of MTA and risk factors have been identified. Hepatotoxicity can result from direct hepatocellular, cholestatic or steatotic injury, through immunogenic pathways or reactivation of viral hepatitis. Selecting an appropriate starting dose for special populations, arranging viral hepatitis screening prior to initiation of relevant MTA and knowing the standards for liver function test (LFT) monitoring are crucial to preventing morbidity and mortality from drug-induced liver injury (DILI) and minimising discontinuation of MTA. This is a comprehensive review on how to interpret LFTs in the light of MTA use, mechanisms of DILI, identification of high risk groups, and measures for preventing and managing hepatotoxicity.
INTRODUCTION: Understanding the mechanism of DILI with MTA, and how to avoid and manage these toxicities is essential for minimising inferior cancer treatment outcomes. An organised and comprehensive overview of MTA-associated hepatotoxicity is lacking; this review aims to fill the gap. Areas covered: A literature review was performed based on published case reports and relevant studies or articles pertaining to the topics on PubMed. Food and Drug Administration drug information documents and search on the US National Library of Medicine LiverTox database was performed for all relevant MTA. Expert opinion: MTA-associated hepatotoxicity is common but rarely fatal. The pattern of hepatotoxicity is predominantly idiosyncratic. Pharmacogenomics show potential in predicting patients at risk of poorly metabolising or developing immunoallergic responses to MTA, but prospective data is scant. Preventing reactivation of viral hepatitis using anti-viral drugs, and avoidance of drug combinations at high risk of negative interactions are the most readily preventable measures for DILI.

PMID: 27187715 [PubMed - as supplied by publisher]

Clinical Zheng-hou Pharmacology: the Missing Link between Pharmacogenomics and Personalized Medicine?

Curr Vasc Pharmacol. 2015;13(4):423-32

Authors: Yu YN, Liu J, Zhang L, Wang Z, Duan DD, Wang YY

Abstract
In Chinese medicine, Zheng-hou, instead of disease, is used to define complex medical problems in clinical practice. In the postgenomics era, it becomes particularly compelling to review the application of Zheng-hou in characterizing complex clinical problems independent of disease or syndrome. While disease or syndrome describes a pathological phenotype or phenotypes, Zheng-hou spells the pathological phenome. Clinical Zheng-hou pharmacology (CZP) is an emerging clinical discipline that aims to leverage breakthroughs in the genome-wide solutions for complex medical problems through a combination of the current "omics" technology and the knowledge of Chinese medicine. The concept of CZP suggests that systematic and standard studies of multiple phenotypes will be important because of the collaborative cross between diversified external and internal factors at different levels both in vitro and in vivo. In this paper, we discuss the novel phenomic approaches to the understanding of Zheng-hou and the link of pharmacogenomics to personalized medicine through CZP, or pharmacophenomics. CZP enables ever-finer mapping of Zheng-hou and detection of dynamic variations in most current omics platforms. Although major challenges still remain in identifying and effectively investigating the diversity of Zheng-hou, CZP is expected to pave new paths to the systemic understanding of medical problems. While still at early stages in the clinical phenome domain, there remains great promise that CZP can help us realize the application of personalized medicine and contribute to rational holistic diagnosis and treatment.

PMID: 25360846 [PubMed - indexed for MEDLINE]

Genetic testing to guide warfarin dosing: Impact of direct oral anticoagulants.

Clin Pharmacol Ther. 2016 May 14;

Authors: Lentz SR

PMID: 27178490 [PubMed - as supplied by publisher]

Therapeutic Application of Pharmacogenomics in Oncology.

AAPS J. 2016 May 13;

Authors: Zhang Y, Somtakoune SD, Cheung C, Listiawan M, Feng X

Abstract
Personalizing cancer treatment has been proved to be difficult for healthcare providers due to the nature of chemotherapies which includes narrow therapeutic indices, severe and potential life-threatening toxicities, and variable response rates and efficacies. Studies in pharmacogenomics (PGx) may help guide clinicians to personalize treatment for cancer patients. Implementing PGx in cancer treatment may offer choices to anticipate differences in drug response, resistance, efficacy, and toxicity within chemotherapeutic agents and targeted immune biologic agents. This can be used to achieve optimization of treatment regimens based on patients' variability. Many of the cancer treatment agents are biologics targeting specific antigens expressed on cancer cells, or blocking stimulators and signal transduction pathways of tumor growth, or enhance anticancer immune responses. It is now crucial for clinicians to understand the important association of clinically important biomarker polymorphisms with the clinical benefits of cancer therapies. By identifying specific PGx biomarker polymorphisms present in cancer cells, physicians can select and tailor a patient's treatment based on his or her genetic profile. PGx-guided cancer treatment may have the ability to improve the survival of patients while avoiding the unnecessary cost due to unresponsive treatment and toxicities of that patients experience.

PMID: 27178043 [PubMed - as supplied by publisher]

Naked-eye fingerprinting of single nucleotide polymorphisms on psoriasis patients.

Nanoscale. 2016 May 13;

Authors: Valentini P, Marsella A, Tarantino P, Mauro S, Baglietto S, Congedo M, Paolo Pompa P

Abstract
We report a low-cost test, based on gold nanoparticles, for the colorimetric (naked-eye) fingerprinting of a panel of single nucleotide polymorphisms (SNPs), relevant for the personalized therapy of psoriasis. Such pharmacogenomic tests are not routinely performed on psoriasis patients, due to the high cost of standard technologies. We demonstrated high sensitivity and specificity of our colorimetric test by validating it on a cohort of 30 patients, through a double-blind comparison with two state-of-the-art instrumental techniques, namely reverse dot blotting and sequencing, finding 100% agreement. This test offers high parallelization capabilities and can be easily generalized to other SNPs of clinical relevance, finding broad utility in diagnostics and pharmacogenomics.

PMID: 27174795 [PubMed - as supplied by publisher]

Ciliary neurotrophic factor upregulates follistatin and Pak1, causes overexpression of muscle differentiation related genes and downregulation of established atrophy mediators in skeletal muscle.

Metabolism. 2016 Jun;65(6):915-25

Authors: Tsompanidis A, Vafiadaki E, Blüher S, Kalozoumi G, Sanoudou D, Mantzoros CS

Abstract
INTRODUCTION: The Ciliary Neurotrophic Factor (CNTF) is a pluripotent cytokine with anorexigenic actions in the hypothalamus that improves insulin sensitivity, increases energy expenditure and induces weight loss. Since CNTF also has an established myotrophic role, we sought to examine whether skeletal muscle contributes to the CNTF-induced metabolic improvement and identify the molecular mechanisms mediating these effects.
METHODS: We used a mouse model of diet-induced obesity, to which high or low CNTF doses were administered for 7days. Whole transcriptome expression levels were analyzed in dissected soleus muscles using microarrays and data were then confirmed using qRT-PCR.
RESULTS: We demonstrate that CNTF administration significantly downregulates leptin, while it upregulates follistatin and Pak1; a molecule associated with insulin sensitization in skeletal muscle. A significant overexpression of muscle differentiation related genes and downregulation of established atrophy mediators was observed.
CONCLUSIONS: The overall gene expression changes suggest an indirect, beneficial effect of CNTF on metabolism, energy expenditure and insulin sensitivity, exerted by the pronounced stimulation of muscle growth, with similarities to the described effect of follistatin and the activation of the Akt pathway in skeletal muscle.

PMID: 27173470 [PubMed - in process]

Combinatorial pharmacogenomic guidance for psychiatric medications reduces overall pharmacy costs in a 1 year prospective evaluation.

Curr Med Res Opin. 2015;31(9):1633-43

Authors: Winner JG, Carhart JM, Altar CA, Goldfarb S, Allen JD, Lavezzari G, Parsons KK, Marshak AG, Garavaglia S, Dechairo BM

Abstract
OBJECTIVES: The objective of this project was to determine pharmacy cost savings and improvement in adherence based on a combinatorial pharmacogenomic test (CPGx ) in patients who had switched or added a new psychiatric medication after having failed monotherapy for their psychiatric disorder.
RESEARCH DESIGN AND METHODS: The prospective project compared 1 year pharmacy claims between a GeneSight CPGx guided cohort and a propensity-matched control group. Patients were project eligible if they augmented or switched to a different antidepressant or antipsychotic medication within the previous 90 days. Following the medication switch or augmentation, pharmacogenomic (PGx) testing was offered to each patient's treating clinician. Pharmacy claims were extracted from the Medco pharmacy claims database for each patient (n = 2168) for 1 year following testing and compared to a 5-to-1 propensity-matched treatment as usual (TAU), standard of care control group (n = 10,880).
MAIN OUTCOME MEASURES: Total pharmacy spend per member per year; adherence.
RESULTS: Patients who received PGx testing saved $1035.60 in total medication costs (both CNS and non-CNS medications) over 1 year compared to the non-tested standard of care cohort (p = 0.007). PGx testing improved adherence compared to standard of care (ΔPDCCPGx = 0.11 vs ΔPDCTAU = -0.01; p < 0.0001). Pharmacy cost savings averaged $2774.53 for patients who were changed to a CPGx congruent medication regimen, compared to those who were not (p < 0.0001).
CONCLUSIONS: PGx testing provides significant 'real world' cost savings, while simultaneously improving adherence in a difficult to treat psychiatric population. Limitations of this study include the lack of therapeutic efficacy follow-up data and possible confounding due to matching only on demographic and psychiatric variables.

PMID: 26086890 [PubMed - indexed for MEDLINE]

[Pharmacogenomics of severe drug hypersensitivity reactions--from bench to bedside].

Przegl Lek. 2015;72(12):779-82

Authors: Porębski G, Dyga W, Stobiecki M, Czarnobilska E

Abstract
Recent remarkable findings of pharmacogenomics and basic scientific research provided insights in the pathogenesis of severe drug hypersensitivity reactions such as drug rush with eosinophilia and systemic symptoms (DRESS), abacavir hypersensitivity syndrome or blistering reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis). There is increasing evidence for the strong associations of certain human leukocyte antigen (HLA) alleles with hypersensitivity to particular drugs. HLA genes may serve as genomic biomarkers of predisposition to severe adverse drug reactions and enable to prevent them. In this paper we review essentials and advances in this area.

PMID: 27024960 [PubMed - indexed for MEDLINE]