Pharmacogenetic predictors of the safety of nonsteroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed medications; however, their use may be associated with the development of numerous adverse reactions. Purpose of work: to analyze the data of studies, in which the influence of pharmacogenetic features of patients on the safety of NSAID therapy was studied. The results of numerous studies show that the safety of NSAIDs may be associated with the CYP2C9, CYP2C8, PTGS1 and PTGS2 polymorphisms. The allele frequency of these genes varies in different ethnic groups. Thus, the development of a personalized approach based on genetic, clinical and demographic, and ethnic factors of patients will improve the safety of NSAID therapy

1. Calatayud S, Esplugues JV. 2016. Chemistry, Pharmacodynamics, and Pharmacokinetics of NSAIDs. NSAIDs and Aspirin. 2016 Springer, Cham. https://doi.org/10.1007/978-3-319-33889-7_1

2. Zhou Y, Boudreau DM, Freedman AN. Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population. Pharmacoepidemiol Drug Saf. 2014 Jan;23(1):43–50. DOI: 10.1002/pds.3463

3. McEvoy L, Carr DF, Pirmohamed M. Pharmacogenomics of NSAIDInduced Upper Gas-trointestinal Toxicity. Front Pharmacol. 2021 Jun 21;12:684162. DOI: 10.3389/fphar.2021.684162

4. Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal antiinflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol. 2020 Oct;180:114147. DOI: 10.1016/j.bcp.2020.114147

5. Arga Z, Sabzwari SRA, Vargova V. Cardiovascular Risk of Nonsteroidal Anti-inflammatory Drugs: An Under-Recognized Public Health Issue. Cureus. 2017 Apr 8;9(4):e1144. DOI: 10.7759/cureus.1144

6. Arfè A, Scotti L, Varas-Lorenzo C, Nicotra F, Zambon A, Kollhorst B, Schink T, Garbe E, Herings R, Straatman H, Schade R, Villa M, Lucchi S, Valkhoff V, Romio S, Thiessard F, Schuemie M, Pariente A, Sturkenboom M, Corrao G; Safety of Non-steroidal Anti-inflammatory Drugs (SOS) Project Consortium. Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study. BMJ. 2016 Sep 28;354:i4857. DOI: 10.1136/bmj.i4857

7. Обжерина А. Ю., Муравьёв Ю. В., Дмитриев В. А., Сычёв Д. А., Кукес В. Г. Значение фармакогенетического тестирования в решении проблемы желудочно-кишечной безопасности применения нестероидных противовоспалительных препаратов. Научно-практическая ревматология. 2009; 47(3):106–110. [Obzerina AY, Muravjov YV, Dmitriev VA, Sychjov DA, Kukes VG. Significance of pharmacogenetic testing in solution of problem of nonsteroid antirheumatic drugs administration gastrointestinal safety. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2009;47(3):106–110. (In Russ).]. URL: https://www.elibrary.ru/download/elibrary_20342160_59541146.pdf. Ссылка активна на 01.12.2022.

8. Moore N, Duong M, Gulmez SE, Blin P, Droz C. Pharmacoepidemiology of non-steroidal anti-inflammatory drugs. Therapie. 2019 Apr;74(2):271–277. DOI: 10.1016/j.therap.2018.11.002

9. Brooks J, Warburton R, Beales IL. Prevention of upper gastrointestinal haemorrhage: current controversies and clinical guidance. Ther Adv Chronic Dis. 2013 Sep;4(5):206–222. DOI: 10.1177/2040622313492188

10. Каратеев А. Е., Насонов Е. Л., Яхно Н. Н. и др. Клинические рекомендации «Рациональное применение нестероидных противовоспалительных препаратов (НПВП) в клинической практике». Современная ревматология. 2015;9(1):4–23. [Karateev AE, Nasonov EL, Yakhno NH, et al. Clinical recommendations “Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice”. Sovremennaya revmatologiya. 2015;9(1):4–23. (In Russ).]. DOI: 10.14412/1996-7012-2015-1-4-23

11. Crooks CJ, West J, Card TR. Upper gastrointestinal haemorrhage and deprivation: a nationwide cohort study of health inequality in hospital admissions. Gut. 2012 Apr;61(4):514–520. DOI: 10.1136/gutjnl-2011-300186

12. Морозова Т. Е., Шацкий Д. А., Ших Н. В., Ших Е. В., Андрущишина Т. Б., Лукина М. В., Качанова А. А., Созаева Ж. А., Шуев Г. Н., Денисенко Н. П., Гришина Е . А., Сычев Д. А. Оценка влияния полиморфизмов CYP2C9*2, CYP2C9*3 на эффективность и безопасность послеоперационного обезболивания кетопрофеном у больных после кардиохирургических вмешательств. Рациональная Фармакотерапия в Кардиологии. 2021;17(4):570–575. [Morozova TE, Shatsky DA, Shikh NV, Shikh EV, Andrushchishina TB, Lukina MV, Kachanova AA, Sozaeva ZhA, Shuev GN, Denisenko NP, Grishina EA, Sychjov DA. Evaluation of the Influence of CYP2C9* 2, CYP2C9*3 Gene Polymorphisms on the Efficacy and Safety of Postoperative Analgesia with Ketoprofen in Patients after Cardiac Surgery. Rational Pharmacotherapy in Cardiology. 2021;17(4):570–575. (In Russ).]. DOI: 10.20996/1819-6446-2021-08-12

13. Spiering W, Kroon AA, Fuss-Lejeune MJ, de Leeuw PW. Genetic contribution to the acute effects of angiotensin II type 1 receptor blockade. J Hypertens. 2005 Apr;23(4):753–758. DOI: 10.1097/01.hjh.0000163143.66965.06

14. Theken KN, Lee CR, Gong L, Caudle KE, Formea CM, Gaedigk A, Klein TE, Agúndez JAG, Grosser T. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clin Pharmacol Ther. 2020 Aug;108(2):191–200. DOI: 10.1002/cpt.1830

15. Денисенко Н. П., Абдуллаев Ш. П., Акмалова К. А. и др. Структура распределения генетических детерминант эффективности и безопасности нестероидных противовоспалительных препаратов в российской популяции: фокус на CYP2C8, PTGS1 и PTGS2. Современная ревматология. 2022;16(1):60–67. [Denisenko NP, Abdullaev ShP, Akmalova KA, et al. Structure of the distribution of genetic determinants of the efficacy and safety of nonsteroidal anti-inflammatory drugs in the Russian population: focus on CYP2C8, PTGS1 and PTGS2. Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2022;16(1):60–67. (In Russ).]. DOI: 10.14412/1996-7012-2022-1-60-67

16. Martínez C, Blanco G, Ladero JM, García-Martín E, Taxonera C, Gamito FG, Diaz-Rubio M, Agúndez JA. Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use. Br J Pharmacol. 2004 Jan;141(2):205–208. DOI: 10.1038/sj.bjp.0705623

17. Pilotto A, Seripa D, Franceschi M, Scarcelli C, Colaizzo D, Grandone E, Niro V, Andriulli A, Leandro G, Di Mario F, Dallapiccola B. Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. Gastroenterology. 2007 Aug;133(2):465–471. DOI: 10.1053/j.gastro.2007.05.025

18. Agúndez JA, García-Martín E, Martínez C. Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine? Expert Opin Drug Metab Toxicol. 2009 Jun;5(6):607–620. DOI: 10.1517/17425250902970998

19. Мирзаев К. В., Федоринов Д. С., Иващенко Д. В., Сычёв Д. А. Мультиэтнический анализ кардиологических фармакогенетических маркеров генов цитохрома Р450 и мембранных транспортёров в российской популяции. Рациональная Фармакотерапия в Кардиологии. 2019;15(3):393–406. [Mirzaev KB, Fedorinov DS, Ivashchenko DV, Sychjov DA. Multi-Ethnic Analysis of Cardiac Pharmacogenetic Markers of Cytochrome P450 and Membrane Transporters Genes in the Russian Population. Rational Pharmacotherapy in Cardiology. 2019;15(3):393–406. (In Russ).]. DOI: 10.20996/1819-6446-2019-15-3-393-406

20. The International Genome Sample Resource (IGSR) [Internet]. URL: https://www.internationalgenome.org/.

21. Нежелательные лекарственные реакции. Взаимодействие лекарственных средств: часть I. Нестероидные противовоспалительные препараты: учеб. пособие / Н. А. Муфазалова, Л. А. Валеева, Р. А. Давлетшин, Д. Д. Сакаева, Л. Ф. Муфазалова. Уфа: ФГБОУ ВО БГМУ Минздрава России, 2020. 195 с. [Undesirable drug reactions. Interaction of drugs: part I. Nonsteroidal anti-inflammatory drugs: textbook. Allowance NA Mufazalova, LA Valeeva, RA Davletshin, DD Sakaeva, LF Mufazalova. URL: http://library.bashgmu.ru/elibdoc/elib746.1.pdf.

22. URL: https://cyberleninka.ru/article/n/rasprostranennostpolimorfizmov-genov-cyp2c8-ptgs-1-2-assotsiirovannyh-s-chuvstvitelnostyuk-nesteroidnym-protivovospalitelnym.

23. Lee YS, Kim H, Wu TX, Wang XM, Dionne RA. Genetically mediated interindividual variation in analgesic responses to cyclooxygenase inhibitory drugs. Clin Pharmacol Ther. 2006 May;79(5):407–418. DOI: 10.1016/j.clpt.2006.01.013

24. St Germaine CG, Bogaty P, Boyer L, Hanley J, Engert JC, Brophy JM. Genetic polymorphisms and the cardiovascular risk of non-steroidal antiinflammatory drugs. Am J Cardiol. 2010 Jun 15;105(12):1740–1745. DOI: 10.1016/j.amjcard.2010.01.352

25. Dobelle E, Aza A, Avellan S, Taillebot V, Ollivier M, Argenson JN. Implantation of the Femoral Component Relative to the Tibial Component in Medial Unicompartmental Knee Arthroplasty: A Clinical, Radiological, and Biomechanical Study. J Arthroplasty. 2022 Jun;37(6S):S82–S87. DOI: 10.1016/j.arth.2022.01.036

26. Hamilton WG, Gargiulo JM, Parks NL. Using pharmacogenetics to structure individual pain management protocols in total knee arthroplasty. Bone Joint J. 2020 Jun;102-B(6_Supple_A):73–78. DOI: 10.1302/0301-620X.102B6.BJJ-2019-1539.R1