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Precision medicine and inflammatory bowel diseases: concept, strategies, future

https://doi.org/10.31146/1682-8658-ecg-190-6-121-129

Abstract

With the advent of modern cellular and genomic technologies, we have become participants in the integration of such areas as personalized, predictive, preventive, and precision medicine (referred to as 4P-medicine), into practical healthcare. In replace of the classic methods of diagnosis and treatment of diseases comes medicine, which makes it possible to predict (anticipate) the disease, and a personalized approach to each patient, taking into account their genetic, biochemical and physiological uniqueness. Precision medicine aims to improve the quality of medical care by opening up an individual approach to the patient and covers a wide range of areas, including drug therapy, genetics, and cause-and-effect relationships in order to make the right decisions based on evidence. 4P-medicine combines knowledge in the field of proteomics, metabolomics, genomics, bioinformatics with classical approaches of anatomy, therapy, laboratory and instrumental diagnostics as well as public health. The purpose of this review is to analyze and summarize the information available to date and to present examples of the application of modern approaches of medicine into clinical practice by diving into the example of inflammatory bowel diseases (IBD). The search for literature containing scientific information about relevant studies was conducted in the PubMed and Google Scholar systems with the use of the following keywords: precision medicine, 4P medicine, inflammatory bowel diseases. Despite significant progress in medicine in general, there is still a long way to go before implementing the principles of precision medicine in the field of IBD, since many clinicians continue to treat patients with IBD symptomatically. However, the use of specific biomarkers and new treatment strategies as described in the review, can significantly accelerate this path and contribute to the improvement of diagnostic and therapeutic approaches.

About the Authors

G. R. Bikbavova
Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
Russian Federation

Galiya R. Bikbavova, Department of Hospital Therapy, Endocrinology, Associate Professor, PhD in Medical sciences

12 Lenina street, 644099 Omsk, Russia



M. A. Livzan
Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
Russian Federation

Mariya A. Livzan, Rector, Head of the Department of Faculty Therapy, Occupational Diseases, Professor, MD

12 Lenina street, 644099 Omsk, Russia



D. G. Novikov
Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
Russian Federation

Dmitry G. Novikov, Head of the Central Research Laboratory, Associate Professor, PhD in Medical sciences

12 Lenina street, 644099 Omsk, Russia



E. A. Bambulskaya
Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
Russian Federation

Evgeniya A. Bambulskaya, 6th year student of the Faculty of Medicine

12 Lenina street, 644099 Omsk, Russia



References

1. Shcherbo, S. N. Shcherbo, D. S. (2019), “Laboratory diagnostics as a basis for 5P medicine”, Bulletin of RSMU, no. 1, p. 5–12. DOI: 10.24075/brsmu.2018.095

2. Baranov V. S. Evolution of predictive medicine. Old ideas and new entities. Medical Genetics. 2017; vol. 16, no. 5, pp. 4–9. (In Russ.)

3. Grens K. FDA to 23 and Me: Stop marketing kits. The Scientist. November 26, 2013. https://www.the-scientist.com/the-nutshell/fda-to-23andme-stop-marketingkits-38354

4. Usova E.V., Popovich M. V., Manyshina A. V., Drakkin OM Responsibility of citizens Beginning health (research in the focus group). Profi lakticheskaya Meditsina. 2021, Vol. 24 Issue 1, p35–44. 10p. (in Russ.) Doi: 10.17116/profmed20212401135.

5. Hood L., AuffraМухин В.Е.y C. Participatory medicine: a driving force for revolutionizing healthcare. Genome Med, 2013;5(12):110. doi:10.1186/gm514

6. Jain K. K. Personalized Medicine. Terra Medica, 2009, no. 1, pp. 4–11 (In Russ.)

7. Shherbo S.N., Shherbo D. S. Personalizirovannaja medicina. [Personalized medicine]. Biological basis- Laboratory technologies. Moscow. RUDN Publ. 2016, Vol. 1–2, pp. 224–437 (In Russ.)

8. U. S. Food and Drug Administration (FDA) Department of Health and Human Services. Paving the Way for Personalized Medicine FDA’s: Role in a New Era of Medical Product Development. 28 october 2013. Available from: https://www.fdanews.com/ext/resources/fi les/10/10–28–13-Personalized- Medicine.pdf

9. König I., Fuchs O., Hansen G., et. al. What is precision medicine? Europ Respir J, 2017, vol. 50, no. 4, pp. 1700391. doi:10.1183/13993003.00391–2017

10. Kosorok M. R., Laber E. B. Precision Medicine. Ann Rev Start Appl, 2019, vol. 6, pp. 263–286. doi:10.1146/annurev- statistics-030718–105251

11. Pal’cev M. A. Personifi cirovannaja medicina. [Personalized medicine]. Nauka v Rossii, 2011, vol. 1, pp. 12–17. (In Russ.) Available from: https://portalus.ru/modules/medecine/rus_readme.php?subaction=showfull&id=1407769757&archive=&start_from=&ucat=&.

12. Aleekseenko S.A., Bagdasaryn A. A., Bakulin I. G., et. al. Brief algorithms of patient management at the stage of primary health. Moscow, Vidox, 2019. 20 p. (In Russ.)

13. Jameson L., Longo J., Dan L. Precision Medicine – Personalized, Problematic, and Promising. N Engl J Med, 2015, vol. 70, no. 10, pp. 612–614. doi:10.1056/NEJMsb1503104.

14. Robinson P. N. Deep phenotyping for precision medicine. Hum Mutat, 2012, vol. 33, no. 5, pp. 777–780. doi:10.1002/ humu.22080.

15. McGrath S., Ghersi D. Building towards precision medicine: empowering medical professionals for the next revolution. BMC Med Genomics, 2016, vol. 9, no. 1, p. 23. doi:10.1186/s12920–016–0183–8.

16. Borg- Bartolo S.P., Boyapati R. K., Satsangi J., Kalla R. Precision medicine in inflammatory bowel disease: concept, progress and challenges. F1000Res, 2020, vol. 9, F1000, FacultyRev-54. doi:10.12688/f1000research.20928.1

17. Prendes-Alvarez S., Nemeroff C. B. Personalized medicine: Prediction of disease vulnerability in mood disorders. Neurosci Lett, 2018; vol. 669, pp. 10–13. doi:10.1016/j.neulet.2016.09.049.

18. Mayeux R. Biomarkers: Potential uses and limitations. NeuroRx, 2004, vol. 1, no. 2, pp. 182–188. doi:10.1602/neurorx.1.2.182.

19. Livzan M.A., Makeikina M. A. Inflammatory bowel diseases: modern aspects of diagnosis and treatment. Gastroenterology. Application to the journal CONSILIUM MEDICUM, 2010, no. 2, pp. 60–65. (In Russ.)

20. Ungaro R., Mehandru S., Allen P. B., Peyrin- Biroulet L., Colombel J-F. Ulcerativecolitis. Lancet, 2017, vol. 389, no. 10080, pp. 1756–1770. doi:10.1016/S0140–6736(16)32126–2

21. Santos M. P.C., Gomes C., Torres J. Familial and Ethnic Risk in Inflammatory Bowel Disease. Ann Gastroenterol, 2018, vol. 31, no. 1, pp. 14–23. doi:10.20524/aog.2017.0208

22. Chen G., Lee S. H., Brion M. A., Montgomery G. W., et. al. Estimation and partitioning of (co)heritability of inflammatory bowel disease from GWAS and immunochip data. Hum Mol Genet, 2014, vol. 23, no. 17, pp. 4710–4720. doi:10.1093/hmg/ddu174

23. Jostins L., Ripke S., Weersma R. K., et. al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature, 2012, vol. 491, no. 7422, pp. 119–124. doi:10.1038/nature11582

24. Liu J. Z., Sommeren SV., Huang H., Ng SC., Alberts R., Takahashi A., et. al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet, 2015, vol. 47, no. 9, pp. 979–986. doi:10.1038/ng.3359

25. Luo Y., de Lange K. M., Jostins L., Moutsianas L., Randall J., Kennedy N. A. Exploring the genetic architecture of inflammatory bowel disease by whole- genome sequencing identifies association at ADCY7. Nat Genet, 2017, vol. 49, no. 2, pp.186–192. doi:10.1038/ng.3761

26. Huang H., Fang M., Jostins L., et. al. Fine-mapping inflammatory bowel disease loci to single- variant resolution. Nature, 2017, vol. 547, no. 7662, pp. 173–178. doi:10.1038/nature22969

27. Makeikina M. A., Livzan M. A. Genetic prognostic factors for the course of non-specific ulcerative colitis. Practical medicine, 2012, vol. 9, no. 65, pp. 133–136. (In Russ.)

28. Cleynen I., Boucher G., Jostins L., et. al. Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study. Lancet, 2016, vol. 387, no. 10014, pp. 156–167. doi:10.1016/S0140–6736(15)00465–1.

29. Goyette P., Boucher G., Mallon D., et. al. High-density mapping of the MHC identifies a shared role for HLADRB1* 01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis. Nat Genet, 2015, vol. 47, no. 2, pp. 172–179. doi:10.1038/ng.3176

30. Ventham N. T., Kennedy N. A., Nimmo E. R., Satsangi J. Beyond Gene Discovery in Inflammatory Bowel Disease: The Emerging Role of Epigenetics. Gastroenterology, 2013, vol. 145, no. 2, pp. 293–308. doi:10.1053/j.gastro.2013.05.050

31. Koizumi K., Alonso S., Miyaki Y., et. al. Array-based identifi cation of common DNA methylation alterations in ulcerative colitis. Int J Oncol, 2012, vol. 40, no. 4, pp. 983–994. doi:10.3892/ijo.2011.1283

32. Häsler R., Feng Z., Bäckdahl L., et. al. A functional methylome map of ulcerative colitis. Genome Res, 2012, vol. 22, no. 11, pp. 2130–2137. doi:10.1101/gr.138347.112

33. Cooke J., Zhang H., Greger L., et. al. Mucosal Genomewide Methylation Changes in Inflammatory Bowel Disease. Inf lamm Bowel Dis, 2012, vol. 18, no. 11, pp. 2128–2137. doi:10.1002/ibd.22942

34. Tahara T., Shibata T., Nakamura M., et. al. Effect of MDR1 gene promoter methylation in patients with ulcerative colitis. Int J Mol Med, 2009, vol. 23, no. 4, pp. 521–527. doi:10.3892/ijmm_00000160

35. Tahara T., Shibata T., Nakamura M., et. al. Promoter methylation of protease-activated receptor (PAR2) is associated with severe clinical phenotypes of ulcerative colitis (UC). Clin Exp Med, 2009, vol. 9, no. 2, pp. 125–130. doi:10.1007/s10238–008–0025-x

36. Paramsothy S., Rosenstein A. K., Mehandru S., Colombel J. F. The current state of the art for biological therapies and new small molecules in inflammatory bowel disease. Mucosal Immuno, 2018, vol. 11, no. 6, 1558–1570. doi:10.1038/s41385–018–0050–3

37. Loukia G.T., Kazuhiro I., Jonathan J. P., Ian M. A., Neville P. Differential patterns of histone acetylation in inflammatory bowel diseases. J Inflamm (lond), 2011, vol. 8, no. 11, p. 1. doi:10.1186/1476–9255–8–1

38. Singh S., George J., Boland B. S., Casteele N. V., Sandborn W. J. Primary Non- Response to Tumor Necrosis Factor Antagonists is Associated with Inferior Response to Second-line Biologics in Patients with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis. J Crohns Colitis, 2018, vol. 12, no. 6, pp. 635–643. doi:10.1093/ecco-jcc/jjy004

39. Wu F., Zikusoka M., Trindade A., Themistocles D., Mary L. H., Bayless T. M., et al. MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2 alpha. Gastroenterology, 2008, vol. 135, no. 5, pp. 1624–1635. doi: 10.1053/j.gastro.2008.07.068

40. Wu F., Zhang S., Dassopoulos T., et al. Identifi cation of microRNAs associated with ileal and colonic Crohn’s disease. Infl amm Bowel Dis, 2010, vol. 16, no. 10, pp.1729–1738. doi:10.1002/ibd.21267

41. Wu F., Guo N. J., Tian H., et al. Peripheral blood microRNAs distinguish active ulcerative colitis and Crohn’s disease. Inflamm Bowel Dis, 2012, vol. 17, no. 1, pp. 241–250. doi: 10.1002/ibd.21450

42. Lee J. C. Predicting the course of IBD: light at the end of the tunnel? Dig Dis, 2012, vol. 30, no. 1, pp. 95–99. doi:10.1159/000341132

43. Belousova E. A., Abdulganieva D. I., Alexeeva O. P., et al. Social and demographic characteristics, features of disease course and treatment options of inflammatory bowel disease in Russia: results of two multicenter studies. Almanac of Clinical Medicine. 2018;46(5):445–463. (In Russ.) Doi:10.18786/2072–0505–2018–46–5–445–463

44. Ivashkin V. T., Shelygin Yu.A., Khalif I. L., et. al. Clinical guide of russian association of gastroenterology and russian association of coloproctology on diagnostics and treatment of crohn’’s disease. Koloproktologija, 2017, vol. 2, no. 60, pp. 7–29. (In Russ.) doi:10.33878/2073–7556–2017–0–2–7–29

45. Travis S. P.L., Farrant J. M., Ricketts C., et al. Predicting outcome in severe ulcerative colitis. Gut, 1996, vol. 38, no. 6, pp. 905–910. doi:10.1136/gut.38.6.905

46. Colombel J-F., Panaccione R., Bossuyt P., et. al. Effect of tight control management on Crohn’s disease (CALM): a multicentre, randomised, controlled phase 3 trial. Lancet, 2017, vol. 390, no. 10114, pp. 2779–2789. doi:10.1016/S0140–6736(17)32641–7

47. Heida A., Park K. T., Rheenen P. F. Clinical Utility of Fecal Calprotectin Monitoring in Asymptomatic Patients with Inflammatory Bowel Disease: A Systematic Review and Practical Guide. Inflam Bowel Dis, 2017, vol. 23, no. 6, pp. 894–902. doi:10.1097/MIB.0000000000001082

48. Florin T. H.J., Paterson E. W.J., Fowler E. V., Radford- Smith G. L. Clinically active Crohn’s disease in the presence of a low C-reactive protein. Scan J Gastroenterol, 2006, vol. 41, no. 3, pp. 306–11. doi:10.1080/00365520500217118

49. Osipenko M.F., Livzan M. A., Skalinskaia M. I., Lialiu ko va E. A. Fecal calprotectin concentration in the differential diagnosis of bowel diseases, 2015, vol. 87, no 2, pp. 30–33. (In Russ.)

50. Ritchie S. C., Würtz P., Nath A. P., et. al. Th e biomarker GlycA is associated with chronic inflammation and predicts long-term risk of severe infection. Cell Syst, 2015, vol. 1, no. 4, pp. 1–9. doi:10.1016/j.cels.2015.09.007

51. Dierckx T., Verstockt B., Vermeire S., Weyenbergh J. GlycA, a Nuclear Magnetic Resonance Spectroscopy Measure for Protein Glycosylation, is a Viable Biomarker for Disease Activity in IBD. J Crohns Colitis, 2019, vol. 13, no. 3, pp. 389–394. doi:10.1093/ecco-jcc/jjy162

52. Kennedy N. A., Heap G. A., Green H. D., et. al. Predictors of anti- TNF treatment failure in anti- TNF-naive patients with active luminal Crohn’s disease: a prospective, multicentre, cohort study. Lancet Gastroenterol Hepatol, 2019, vol. 4, no. 5, pp. 341–353. doi:10.1016/S2468–1253(19)30012–3

53. Mitrev N., Casteele N. V., Seow C. H., et. al. Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases. Aliment Pharmacol Ther, 2017, vol. 46, no. 11–12, pp. 1037–1053. doi:10.1111/apt.14368

54. Ricciuto A., Dhaliwal J., Walters T. D., Griffiths A. M., Church P. C. Clinical Outcomes With Therapeutic Drug Monitoring in Inflammatory Bowel Disease: A Systematic Review With Meta- Analysis. J Crohns Colitis. 2018, vol. 12, no. 11, pp. 1302–1315. doi:10.1093/ecco-jcc/jjy109

55. Dean L., Pratt V., McLeod H., Rubinstein W., Dean L., Kattman B., et. al. Azathioprine Th erapy and TPMT and NUDT15 Genotype. Medical Genetics Summaries. 2012, sep. 20. Available from: https://www.ncbi.nlm.nih.gov/books/NBK100661/

56. Boer N. K.H., Peyrin-Biroulet L., Jharap B., et. al. Thiopurines in Inflammatory Bowel Disease: New Findings and Perspectives. J Crohns Colitis, 2018, vol. 12, no. 5, pp. 610–620. Doi: 10.1093/ecco-jcc/jjx181

57. Pereira M. S., Maia L., Azevedo L. F., et. al. A [Glyco] biomarker that Predicts Failure to Standard Th erapy in Ulcerative Colitis Patients. J Crohns Colitis. 2019, vol. 13, no.1, pp. 39–49. doi:10.1093/ecco-jcc/jjy139

58. Chambrun G. P., PeyrinBiroulet L., Lémann M., Colombel J-F. Clinical implications of mucosal healing for the management of IBD. Nat Rev Gastroenterol Hepatol, 2010, vol. 7, no. 1, pp. 15–29. doi:10.1038/nrgastro.2009.203

59. Fumery M., Singh S., Dulai P. S., Gower- Rousseau C., Peyrin- Biroulet L., Sandborn W. J. Natural history of adult ulcerative colitis in population- based cohorts: A systematic review. Clini Gastroenterol Hepatol, 2018, vol. 16, no. 3, pp. 343–356. doi:10.1016/j.cgh.2017.06.016

60. Turner D., Ricciuto A., LewisA., et. al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to- Target strategies in IBD. Gastroenterology, 2021, vol. 161, no. 5, pp. 1570–1583. doi:10.1053/ j.gastro.2020.12.031

61. Peyrin-Biroulet L., Sandborn W., Sands B. E., Reinisch W., Bemelman W., Bryant R. V., et. al. Selecting Therapeutic targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. The Am J Gastroenterolog, 2015, vol. 110, no. 9, pp. 1324–1338. doi:10.1038/ajg.2015.233

62. Arijs I., Hertogh G. D., Lemmens B., et. al. Effect of vedolizumab (anti-alpha4beta7-integrin) therapy on histological healing and mucosal gene expression in patients with UC. Gut. 2018, vol. 67, no. 1, pp. 43–52. doi:10.1136/gutjnl-2016–312293

63. Yzet C., Ungaro R., Bossuyt P., et. al. OP35 Endoscopic and deep remission at 1 year prevents disease progression in early Crohn’s disease: Long-term data from CALM. Journal of Crohn’s and Colitis. 2019, vol. 13, S024–S025. doi:10.1093/ecco-jcc/jjy222.032

64. Bryant V. R., Costello P. S., Schoeman S., et. al. Limited uptake of ulcerative colitis “treat to target” recommendations in real-world practice. J Gastroenterol Hepatol. 2018, 33, no. 3, pp. 599–607. doi:10.1111/jgh.13923


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Bikbavova G.R., Livzan M.A., Novikov D.G., Bambulskaya E.A. Precision medicine and inflammatory bowel diseases: concept, strategies, future. Experimental and Clinical Gastroenterology. 2021;1(6):121-129. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-190-6-121-129

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