MyPGx® Abstract booklet July 2018 Version number: 003 Content I. General information abstracts – Pharmacogenetics (PGx), single nucleotide polymorphisms (SNPs) and adverse drug reactions (ADRs) 2 II. Psychiatry - MyPSY 10 III. Rheumatology - MyRHUMA 14 IV. Neuology – MyNEURO 16 V. Oncology – MyONCO 18 VI. Cardiology– MyCARDIO 21 VII. APPENDIX 1: U.S.Food & Drug administration (FDA) PGx Biomarker in drug labelling 26 VIII. APPENDIX 2: Genetic biomarkers associated with inter-individual differences in drug pharmacokinetic or pharmacodynamics parameters 42 © 2018 SYNLAB International GmbH. All rights reserved. MyPGx® is a registered trade mark of SYNLAB International GmbH. 1 I. General information abstracts – Pharmacogenetics (PGx), single nucleotide polymorphisms (SNPs) and adverse drug reactions (ADRs) A Survey on Polypharmacy and Use of Inappropriate Medications Rambhade, S., Chakarborty, A., Shrivastava, A., Patil, U. K., & Rambhade, A. (2012). A survey on polypharmacy and use of inappropriate medications. Toxicology international, 19(1), 68. In the past, polypharmacy was referred to the mixing of many drugs in one prescription. Today polypharmacy implies to the prescription of too many medications for an individual patient, with an associated higher risk of adverse drug reactions (ADRs) and interactions. Situations certainly exist where the combination therapy or polytherapy is the used for single disease condition. Polypharmacy is a problem of substantial importance, in terms of both direct medication costs and indirect medication costs resulting from drug-related morbidity. Polypharmacy increases the risk of side effects and interactions. Moreover it is a preventable problem. A retrospective study was carried out at Bhopal district (Capital of Madhya Pradesh, India) in the year of September-November 2009 by collecting prescriptions of consultants at various levels of health care. The tendency of polypharmacy was studied and analyzed under the various heads in the survey. Available data suggests that polypharmacy is a widespread problem, and physician, clinical pharmacists and patients are all responsible. These risks can be minimized through identifying the prevalence of this potential problem in a high-risk population and by increasing awareness among patients and healthcare professionals. Physicians and clinical pharmacists have the potential to c ombating this problem through a variety of interventions such as reducing the number of medications taken, reducing the number of doses taken, increasing patient adherence, preventing ADRs, improving patient quality of life and decreasing facility and drug costs. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients Pirmohamed, M., James, S., Meakin, S., Green, C., Scott, A. K., Walley, T. J., ... & Breckenridge, A. M. (2004). Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. Bmj, 329(7456), 15-19. Objective: To ascertain the current burden of adverse drug reactions (ADRs) through a prospective analysis of all admissions to hospital. Design: Prospective observational study. Setting: Two large general hospitals in Merseyside, England. Participants: 18 820 patients aged > 16 years admitted over six months and assessed for cause of admission. Main outcome measures: Prevalence of admissions due to an ADR, length of stay, avoid ability, and outcome. Results: There were 1225 admissions related to an ADR, giving a prevalence of 6.5%, with the ADR directly leading to the admission in 80% of cases. The median bed stay was eight days, accounting for 4% of the hospital bed capacity. The projected annual cost of such admissions to the NHS is 466m pounds sterling (706m Euros, 847m dollars). The overall fatality was 0.15%. Most reactions were either definitely or possibly avoidable. Drugs most commonly implicated in causing these admissions included low dose aspirin, diuretics, warfarin, and non-steroidal anti-inflammatory drugs other than aspirin, the most common reaction being gastrointestinal bleeding. Conclusion: The burden of ADRs on the NHS is high, accounting for considerable morbidity, mortality, and extra costs. Although many of the implicated drugs have proved benefit, measures need to be put into place to reduce the burden of ADRs and thereby further improve the benefit:harm ratio of the drugs. © 2018 SYNLAB International GmbH. All rights reserved. MyPGx® is a registered trade mark of SYNLAB International GmbH. 2 Clinical and economic burden of adverse drug reactions Sultana, J., Cutroneo, P., & Trifirò, G. (2013). Clinical and economic burden of adverse drug reactions. Journal of pharmacology & pharmacotherapeutics, 4(Suppl1), S73. Adverse drug reactions (ADRs) are unwanted drug effects that have considerable economic as well as clinical costs as they often lead to hospital admission, prolongation of hospital stay and emergency department visits. Randomized controlled trials (RCTs) are the main premarketing methods used to detect and quantify ADRs but these have several limitations, such as limited study sample size and limited heterogeneity due to the exclusion of the frailest patients. In addition, ADRs due to inappropriate medication use occur often in the real world of clinical practice but not in RCTs. Postmarketing drug safety monitoring through pharmacovigilance activities, including mining of spontaneous reporting and carrying out observational prospective cohort or retrospective database studies, allow longer follow-up periods of patients with a much wider range of characteristics, providing valuable means for ADR detection, quantification and where possible reduction, reducing healthcare costs in the process. Overall, pharmacovigilance is aimed at identifying drug safety signals as early as possible, thus minimizing potential clinical and economic consequences of ADRs. The goal of this review is to explore the epidemiology and the costs of ADRs in routine care. Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial Elliott, L. S., Henderson, J. C., Neradilek, M. B., Moyer, N. A., Ashcraft, K. C., & Thirumaran, R. K. (2017). Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial. PloS one, 12(2), e0170905 Background: In polypharmacy patients under home health management, pharmacogenetic testing coupled with guidance from a clinical decision support tool (CDST) on reducing drug, gene, and cumulative interaction risk may provide valuable insights in prescription drug treatment, reducing re-hospitalization and emergency department (ED) visits. We assessed the clinical impact of pharmacogenetic profiling integrating binary and cumulative drug and gene interaction warnings on home health polypharmacy patients. Methods and findings: This prospective, open-label, randomized controlled trial was conducted at one hospital- based home health agency between February 2015 and February 2016. Recruitment came from patient referrals to home health at hospital discharge. Eligible patients were aged 50 years and older and taking or initiating treatment with medications with potential or significant drug-gene-based interactions. Subjects (n = 110) were randomized to pharmacogenetic profiling (n = 57). The study pharmacist reviewed drug-drug, drug-gene, and cumulative drug and/or gene interactions using the YouScript® CDST to provide drug therapy recommendations to clinicians. The control group (n = 53) received treatment as usual including pharmacist guided medication management using a standard drug information resource. The primary outcome measure was the number of re-hospitalizations and ED visits at 30 and 60 days after discharge from the hospital. The mean number of re-hospitalizations per patient in the tested vs. untested group was 0.25 vs. 0.38 at 30 days (relative risk (RR), 0.65; 95% confidence interval (CI), 0.32–1.28; P = 0.21) and 0.33 vs. 0.70 at 60 days following enrollment (RR, 0.48; 95% CI, 0.27–0.82; P = 0.007). The mean number of ED visits per patient in the tested vs. © 2018 SYNLAB International GmbH. All rights reserved. MyPGx® is a registered trade mark of SYNLAB International GmbH. 3 untested group was 0.25 vs. 0.40 at 30 days (RR, 0.62; 95% CI, 0.31–1.21; P = 0.16) and 0.39 vs. 0.66 at 60 days (RR, 0.58; 95% CI, 0.34–0.99; P = 0.045). Differences in composite outcomes at 60 days (exploratory endpoints) were also found. Of the total 124 drug therapy recommendations passed on to clinicians, 96 (77%) were followed. These findings should be verified with additional prospective confirmatory studies involving real-world applications in larger populations to broaden acceptance in routine clinical practice. Conclusions: Pharmacogenetic testing of polypharmacy patients aged 50 and older, supported by an appropriate CDST, considerably reduced re-hospitalizations and ED visits at 60 days following enrollment resulting in potential health resource utilization savings and improved healthcare. Cost-Effectiveness of Pharmacogenomic and Pharmacogenetic Test-Guided Personalized Therapies: A Systematic Review of the Approved Active Substances for Personalized Medicine in Germany Plöthner, M., Ribbentrop, D., Hartman, J. P., & Frank, M. (2016). Cost-effectiveness of pharmacogenomic and pharmacogenetic test-guided personalized therapies: a systematic review of