This is getting personal: Precision medicine in the care of Inflammatory Bowel Disease patients in 2024

TMED Blog

| 10 October 2024

Written by Christine Ha, MSc '26 (Candidate)

On October 3, 2024, our TMED students attended the Medical Grand Rounds and had the privilege to listen to Dr. Mark Ropeleski’s presentation on precision medicine in the care of Inflammatory Bowel Disease (IBD) patients.

IBD is an autoimmune disorder that is characterized by chronic inflammation in the gastrointestinal tract (1). Two major categories of IBD are ulcerative colitis and Crohn’s disease (1). Although current understanding suggests that the etiopathology of IBD is multifactorial, involving genetics, immune dysregulation, and environmental risk factors, the exact cause remains unclear (2). Some studies report that IBD is caused by persistent immune responses to gut microbiota, which are essential for maintaining structural integrity of the intestine, nutrient metabolism, and protection against other harmful pathogens (1,3). Thus, damage to the gut microbiota can deteriorate the lining of the gastrointestinal tract and increase gut permeability, thereby exacerbating the inflammation (4).

Dr. Ropeleski identifies IBD as a heterogenous disease, given its variability in its pathogenesis, disease onset, phenotypes, prognosis, and response to treatment. Initial genome-wide association studies have identified more than 240 genetic risk loci associated with IBD susceptibility, yet its potential for hereditability remains unknown (5,6). While genetic studies have investigated IBD susceptibility, limited studies support its role in prognosis and choice of treatment due to its phenotype differences and individual response to therapy (7). Hence, these limitations call for future studies to further investigate the cellular networks of IBD using both retrospective and prospective analysis.

Given the heterogeneity nature of IBD and absence of curative therapies, immunomodulators and anti-TNFa inhibitors are prescribed for symptom management to achieve long-term remission and reduce inflammation (8). However, in cases when medications fail to control inflammation, surgery is performed to open or excise severely inflamed intestinal segments (8). Despite these existing therapies, current literature has introduced the concept of deep remission and mucosal healing during its early stages as a therapeutic potential to reduce disease progression (8). Dr. Ropeleski presents the idea of precision medicine to develop personalized treatments for IBD patients by accounting clinical, genetic, and environmental factors (9). Using this medical model, he emphasizes that future longitudinal prospective studies should stratify data with early diagnosed IBD patients to identify prognostic biomarkers and incorporate top-down treatment approaches (10). Studies also report that prognostic biomarkers does show potential in predicting which patients can benefit from early therapies (10).

During Dr. Ropeleski’s discussion with TMED students, he shares his career journey as a gastroenterologist and clinician scientist at Queen’s University. He highlights the importance of top-down rather than bottom-up approaches to elucidate IBD’s heterogeneity and integrate these findings into clinical practices. He also discusses the implications of JAK inhibitors, Remicade, and anti-TNF inhibitors for IBD management. Particularly, he expresses concerns surrounding Remicade as he believes that while it is accessible and cost-effective, further clinical trials must demonstrate its safety and efficacy. Though prior studies demonstrate the association between prognostic biomarkers and IBD treatment, Dr. Ropeleski stresses the need for prospective studies to identify those specific biomarkers. Ultimately, he hopes to translate this knowledge into personalized and early treatment strategies to improve patient outcomes.

References

1. Zhang YZ, Li YY. Inflammatory bowel disease: Pathogenesis. World J Gastroenterol. 2014;20(1):91-99. doi:10.3748/wjg.v20.i1.91

2. Cai Z, Wang S, Li J. Treatment of Inflammatory Bowel Disease: A Comprehensive Review. Front Med. 2021;8. doi:10.3389/fmed.2021.765474

3. Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Reddy DN. Role of the normal gut microbiota. World J Gastroenterol. 2015;21(29):8787-8803. doi:10.3748/wjg.v21.i29.8787

4. Khan I, Ullah N, Zha L, et al. Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome. Pathogens. 2019;8(3):126. doi:10.3390/pathogens8030126

5. Turpin W, Goethel A, Bedrani L, Croitoru M Kenneth. Determinants of IBD Heritability: Genes, Bugs, and More. Inflammatory Bowel Diseases. 2018;24(6):1133-1148. doi:10.1093/ibd/izy085

6. Hu S, Uniken Venema WT, Westra HJ, et al. Inflammation status modulates the effect of host genetic variation on intestinal gene expression in inflammatory bowel disease. Nat Commun. 2021;12(1):1122. doi:10.1038/s41467-021-21458-z

7. Cleynen I, Boucher G, Jostins L, et al. Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study. The Lancet. 2016;387(10014):156-167. doi:10.1016/S0140-6736(15)00465-1

8. Hazel K, O’Connor A. Emerging treatments for inflammatory bowel disease. Therapeutic Advances in Chronic Disease. 2020;11:2040622319899297. doi:10.1177/2040622319899297

9. Akhoon N. Precision Medicine: A New Paradigm in Therapeutics. Int J Prev Med. 2021;12:12. doi:10.4103/ijpvm.IJPVM_375_19

10. Noor NM, Lee JC, Bond S, et al. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn’s disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol Hepatol. 2024;9(5):415-427. doi:10.1016/S2468-1253(24)00034-7

This is getting personal: Precision medicine in the care of Inflammatory Bowel Disease patients in 2024

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This is getting personal: Precision medicine in the care of Inflammatory Bowel Disease patients in 2024

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