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Toward Personalized Therapy in Inflammatory Bowel Disease

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Molecular Genetics of Inflammatory Bowel Disease

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Abstract

Inflammatory bowel disease (IBD) is a heterogeneous disease with patients experiencing varying disease courses and response to therapy. Developing precision medicine approaches is of great interest and importance to improve care for IBD patients. Recent advances have the potential to change the way clinicians stratify patients and then select the most appropriate treatment based on an individualized assessment of risk of complications and drug response. In this chapter, we provide concluding remarks on the current evidence and potential for genomics in IBD care and future directions to bring precision medicine approaches to the clinic.

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References

  1. Colombel J-F, Narula N, Peyrin-Biroulet L (2017) Management strategies to improve outcomes of patients with inflammatory bowel diseases. Gastroenterology 152:351–361.e5. https://doi.org/10.1053/j.gastro.2016.09.046

    Article  PubMed  Google Scholar 

  2. Peyrin-Biroulet L, Sandborn W, Sands BE et al (2015) Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol 110:1324–1338. https://doi.org/10.1038/ajg.2015.233

    Article  CAS  PubMed  Google Scholar 

  3. Colombel J-F, Panaccione R, Bossuyt P et al (2018) Effect of tight control management on Crohn’s disease (CALM): a multicentre, randomised, controlled phase 3 trial. Lancet 390:2779–2789. https://doi.org/10.1016/S0140-6736(17)32641-7

    Article  Google Scholar 

  4. Ungaro R, Mehandru S, Allen PB et al (2017) Ulcerative colitis. Lancet 389:1756–1770. https://doi.org/10.1016/S0140-6736(16)32126-2

    Article  PubMed  Google Scholar 

  5. Torres J, Mehandru S, Colombel J-F, Peyrin-Biroulet L (2017) Crohn’s disease. Lancet 389:1741–1755. https://doi.org/10.1016/S0140-6736(16)31711-1

    Article  PubMed  Google Scholar 

  6. Siegel CA (2018) Refocusing IBD patient management: personalized, proactive, and patient-centered care. Am J Gastroenterol 113:1440–1443. https://doi.org/10.1038/s41395-018-0246-x

    Article  PubMed  Google Scholar 

  7. Ben-Horin S, Kopylov U, Chowers Y (2014) Optimizing anti-TNF treatments in inflammatory bowel disease. Autoimmun Rev 13:24–30. https://doi.org/10.1016/j.autrev.2013.06.002

    Article  CAS  PubMed  Google Scholar 

  8. van der Valk ME, Mangen M-JJ, Leenders M et al (2014) Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFα therapy: results from the COIN study. Gut 63:72–79. https://doi.org/10.1136/gutjnl-2012-303376

    Article  PubMed  Google Scholar 

  9. Bonovas S, Fiorino G, Allocca M et al (2016) Biologic therapies and risk of infection and malignancy in patients with inflammatory bowel disease: a systematic review and network meta-analysis. Clin Gastroenterol Hepatol 14:1385–1397.e10. https://doi.org/10.1016/j.cgh.2016.04.039

    Article  PubMed  Google Scholar 

  10. Cleynen I, Boucher G, Jostins L et al (2016) Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study. Lancet 387:156–167. https://doi.org/10.1016/S0140-6736(15)00465-1

    Article  PubMed  PubMed Central  Google Scholar 

  11. Jostins L, Ripke S, Weersma RK et al (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119–124. https://doi.org/10.1038/nature11582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Liu JZ, van Sommeren S, Huang H et al (2015) Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet 47:979–986. https://doi.org/10.1038/ng.3359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Duerr RH, Taylor KD, Brant SR et al (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463. https://doi.org/10.1126/science.1135245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Pidasheva S, Trifari S, Phillips A et al (2011) Functional studies on the IBD susceptibility gene IL23R implicate reduced receptor function in the protective genetic variant R381Q. PLoS One 6:e25038. https://doi.org/10.1371/journal.pone.0025038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Adler J, Rangwalla SC, Dwamena BA, Higgins PDR (2011) The prognostic power of the NOD2 genotype for complicated Crohn’s disease: a meta-analysis. Am J Gastroenterol 106:699–712. https://doi.org/10.1038/ajg.2011.19

    Article  CAS  PubMed  Google Scholar 

  16. Torres J, Colombel J-F (2016) Genetics and phenotypes in inflammatory bowel disease. Lancet 387:98–100. https://doi.org/10.1016/S0140-6736(15)00464-X

    Article  PubMed  Google Scholar 

  17. Kugathasan S, Denson LA, Walters TD et al (2017) Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study. Lancet 389:1710–1718. https://doi.org/10.1016/S0140-6736(17)30317-3

    Article  PubMed  PubMed Central  Google Scholar 

  18. Lee JC, Biasci D, Roberts R et al (2017) Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn’s disease. Nat Genet 49:262–268. https://doi.org/10.1038/ng.3755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lee JC, Lyons PA, McKinney EF et al (2011) Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis. J Clin Invest 121:4170–4179. https://doi.org/10.1172/JCI59255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Siegel CA, Horton H, Siegel LS et al (2016) A validated web-based tool to display individualised Crohn’s disease predicted outcomes based on clinical, serologic and genetic variables. Aliment Pharmacol Ther 43:262–271. https://doi.org/10.1111/apt.13460

    Article  CAS  PubMed  Google Scholar 

  21. Feuerstein JD, Nguyen GC, Kupfer SS et al (2017) American gastroenterological association institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology 153:827–834. https://doi.org/10.1053/j.gastro.2017.07.032

    Article  PubMed  Google Scholar 

  22. Moriyama T, Nishii R, Perez-Andreu V et al (2016) NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity. Nat Genet 48:367–373. https://doi.org/10.1038/ng.3508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schaeffeler E, Jaeger SU, Klumpp V et al (2019) Impact of NUDT15 genetics on severe thiopurine-related hematotoxicity in patients with European ancestry. Genet Med. https://doi.org/10.1038/s41436-019-0448-7

  24. Heap GA, Weedon MN, Bewshea CM et al (2014) HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants. Nat Genet 46:1131–1134. https://doi.org/10.1038/ng.3093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wilson A, Jansen LE, Rose RV et al (2018) HLA-DQA1-HLA-DRB1 polymorphism is a major predictor of azathioprine-induced pancreatitis in patients with inflammatory bowel disease. Aliment Pharmacol Ther 47:615–620. https://doi.org/10.1111/apt.14483

    Article  CAS  PubMed  Google Scholar 

  26. Pierik M, Vermeire S, Steen KV et al (2004) Tumour necrosis factor-alpha receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab. Aliment Pharmacol Ther 20:303–310. https://doi.org/10.1111/j.1365-2036.2004.01946.x

    Article  CAS  PubMed  Google Scholar 

  27. Niess JH, Klaus J, Stephani J et al (2012) NOD2 polymorphism predicts response to treatment in Crohn’s disease--first steps to a personalized therapy. Dig Dis Sci 57:879–886. https://doi.org/10.1007/s10620-011-1977-3

    Article  CAS  PubMed  Google Scholar 

  28. Lügering A, Schmidt M, Lügering N et al (2001) Infliximab induces apoptosis in monocytes from patients with chronic active Crohn’s disease by using a caspase-dependent pathway. Gastroenterology 121:1145–1157

    Article  PubMed  Google Scholar 

  29. Scallon BJ, Moore MA, Trinh H et al (1995) Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine 7:251–259. https://doi.org/10.1006/cyto.1995.0029

    Article  CAS  PubMed  Google Scholar 

  30. Bek S, Nielsen JV, Bojesen AB et al (2016) Systematic review: genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases. Aliment Pharmacol Ther 44:554–567. https://doi.org/10.1111/apt.13736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Verstockt B, Verstockt S, Blevi H et al (2018) TREM-1, the ideal predictive biomarker for endoscopic healing in anti-TNF-treated Crohn’s disease patients? Gut. https://doi.org/10.1136/gutjnl-2018-316845

  32. Barber GE, Yajnik V, Khalili H et al (2016) Genetic markers predict primary non-response and durable response to anti-TNF biologic therapies in Crohn’s disease. Am J Gastroenterol 111:1816–1822. https://doi.org/10.1038/ajg.2016.408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. West NR, Hegazy AN, Owens BMJ et al (2017) Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease. Nat Med 23:579–589. https://doi.org/10.1038/nm.4307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dulai PS, Boland BS, Singh S et al (2018) Development and validation of a scoring system to predict outcomes of vedolizumab treatment in patients with Crohn’s disease. Gastroenterology 155:687–695.e10. https://doi.org/10.1053/j.gastro.2018.05.039

    Article  PubMed  Google Scholar 

  35. Ananthakrishnan AN, Luo C, Yajnik V et al (2017) Gut microbiome function predicts response to anti-integrin biologic therapy in inflammatory bowel diseases. Cell Host Microbe 21:603–610.e3. https://doi.org/10.1016/j.chom.2017.04.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Vermeire S, O’Byrne S, Keir M et al (2014) Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial. Lancet 384:309–318. https://doi.org/10.1016/S0140-6736(14)60661-9

    Article  CAS  PubMed  Google Scholar 

  37. Sands BE, Chen J, Feagan BG et al (2017) Efficacy and safety of MEDI2070, an antibody against interleukin 23, in patients with moderate to severe Crohn’s disease: a phase 2a study. Gastroenterology 153:77–86.e6. https://doi.org/10.1053/j.gastro.2017.03.049

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Ryan C. Ungaro & Jean-Frederic Colombel

Authors
  1. Ryan C. Ungaro
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  2. Jean-Frederic Colombel
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Corresponding author

Correspondence to Jean-Frederic Colombel .

Editor information

Editors and Affiliations

  1. Gastroenterology unit, Patient Area Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden

    Charlotte Hedin

  2. Montreal Heart Institute and Université de Montréal, Montréal, QC, Canada

    John D. Rioux

  3. School of Biological Sciences, Monash University, Clayton, VIC, Australia

    Mauro D'Amato

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Ungaro, R.C., Colombel, JF. (2019). Toward Personalized Therapy in Inflammatory Bowel Disease. In: Hedin, C., Rioux, J., D'Amato, M. (eds) Molecular Genetics of Inflammatory Bowel Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-28703-0_17

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