Using Immunosuppressive Therapies to Treat Inflammatory Bowel Diseases (IBD) in the Post‑Cancer Setting

Authors

  • Rana Kandel, MD Division of Gastroenterology, Department of Medicine, University of Ottawa, Ottawa, ON
  • Sanjay K. Murthy, MD, MSc, FRCPC Division of Gastroenterology, Department of Medicine, University of Ottawa, Ottawa, ON

DOI:

https://doi.org/10.58931/cibdt.2025.3139

Abstract

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD), and ulcerative colitis (UC), are chronic immune-mediated inflammatory disorders (IMID) affecting both intestinal and extraintestinal organs. Chronic intestinal inflammation causes multifocal DNA damage, increasing the risks of intestinal cancers. While the widespread use of effective biologic and small molecule therapies and intensified immune modulating (IM) regimens in recent years may have contributed toward declining colorectal cancer risks, these treatments could have introduced unexpected cancer risks in organs not directly affected by IBD due to reduced immune surveillance. Among individuals with IBD, the use of thiopurines has been frequently associated with risks of lymphoma, non‑melanoma skin cancer (NMSC), and cervical cancer. Several large studies have also reported increased risks of lymphoma, and melanoma associated with anti-tumour necrosis factor alpha (anti‑TNF) therapies, although other studies have not shown these associations. A randomized controlled trial (RCT) in elderly individuals with rheumatoid arthritis (RA) and cardiovascular risk factors reported a slightly increased all‑cause cancer risk with the non-selective Janus kinase inhibitor (JAKi), tofacitinib. Other immunosuppressive (IS) therapies, including methotrexate, anti-interleukin (IL)‑12/23 or anti‑IL-23 therapies, anti-α4β7 integrin therapy, JAK-1-selective inhibitors (upadacitinib), and sphingosine-1-phosphate receptor agonists, have not been associated with increased cancer risks to date. However, some of these newer therapies have only been available for a few years.   

Given the low absolute risk of treatment‑related cancers, controlling underlying IBD with IS therapies is typically prioritized to improve quality of life and reduce IBD-related complications. However, the decision to start or continue IS therapy in individuals with current or prior malignancy is more complex, as immune surveillance may be more crucial for these patients. Clinical trials generally exclude patients with a cancer history, which limits the available evidence on cancer recurrence risks associated with specific therapies. Additionally, some cytotoxic chemotherapy regimens can control IBD for prolonged periods, suggesting that additional immunomodulation may be unnecessary, and potentially harmful, during cancer treatment. Conversely, hormonal, radiation, and immune checkpoint inhibitor therapies have been associated with increased risks of IBD flares. Therefore, a careful and collaborative approach with oncologists is essential for the optimal management of IBD patients diagnosed with cancer.

Recently, the European Crohn’s and Colitis Organization (ECCO) and the American Gastroenterological Association (AGA) released practice recommendations regarding the use of IS therapies in individuals with IBD in the post‑cancer setting. This review summarizes the evidence regarding cancer risks associated with specific IBD therapies in this context and presents a management approach based on both scientific and practical considerations.

Author Biographies

Rana Kandel, MD , Division of Gastroenterology, Department of Medicine, University of Ottawa, Ottawa, ON

Dr. Kandel is currently a fourth-year Gastroenterology resident at the University of Ottawa. She completed her undergraduate medical degree at the University of Ottawa in 2021 and Core Internal Medicine training at Queen’s University in 2024. Her clinical interests include Inflammatory Bowel Diseases (IBD) in which she intends to pursue an advanced IBD fellowship training.

Sanjay K. Murthy, MD, MSc, FRCPC, Division of Gastroenterology, Department of Medicine, University of Ottawa, Ottawa, ON

Dr. Murthy is an Associate Professor of Medicine at the University of Ottawa, Gastroenterologist at the Ottawa Hospital IBD Centre and Scientist at The Ottawa Hospital Research Institute. He completed his medical degree at the University of Ottawa, Internal Medicine Residency at the University of Manitoba and Gastroenterology Residency at the University of Toronto. He completed advanced clinical and research fellowships in inflammatory bowel diseases (Mount Sinai Hospital, Toronto), clinical nutrition (Toronto General Hospital) and diagnostic endoscopy (University of Mainz, Germany) and an M.Sc. degree in Clinical Epidemiology and Health Care Research (University of Toronto). Dr. Murthy’s research program uses clinical and health administrative data to conduct epidemiological studies, pragmatic trials and clinical prediction models, which he applies to the study of inflammatory bowel diseases (IBD) and gastrointestinal cancers. He is currently leading multiple national studies evaluating cancer epidemiology and prevention in IBD and is supported by a Faculty of Medicine Research Chair in IBD from the University of Ottawa.

References

Rubin CE, Haggitt RC, Burmer GC, Brentnall TA, Stevens AC, Levine DS, et al. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. Gastroenterology. 1992;103(5):1611-1620. doi:10.1016/0016-5085(92)91185-7 DOI: https://doi.org/10.1016/0016-5085(92)91185-7

Lyda MH, Noffsinger A, Belli J, Fenoglio-Preiser CM. Microsatellite instability and K-ras mutations in patients with ulcerative colitis. Hum Pathol. 2000;31(6):665-671. doi:10.1053/hupa.2000.7643 DOI: https://doi.org/10.1053/hupa.2000.7643

Sandborn WJ, Rebuck R, Wang Y, Zou B, Adedokun OJ, Gasink C, et al. Five-year efficacy and safety of ustekinumab treatment in Crohn’s disease: the IM-UNITI trial. Clin Gastroenterol Hepatol. 2022;20(3):578-590.e574. doi:10.1016/j.cgh.2021.02.025 DOI: https://doi.org/10.1016/j.cgh.2021.02.025

Lutgens MW, van Oijen MG, van der Heijden GJ, Vleggaar FP, Siersema PD, Oldenburg B. Declining risk of colorectal cancer in inflammatory bowel disease: an updated meta-analysis of population-based cohort studies. Inflamm Bowel Dis. 2013;19(4):789-799. doi:10.1097/MIB.0b013e31828029c0 DOI: https://doi.org/10.1097/MIB.0b013e31828029c0

Shah SC, Itzkowitz SH. Colorectal cancer in inflammatory bowel disease: mechanisms and management. Gastroenterology. 2022;162(3):715-730.e713. doi:10.1053/j.gastro.2021.10.035 doi:10.1053/j.gastro.2021.10.035 DOI: https://doi.org/10.1053/j.gastro.2021.10.035

Murthy SK, Tandon P, Matthews P, Ahmed F, Pugliese M, Taljaard M, et al. A population-based matched cohort study of digestive system cancer incidence and mortality in individuals with and without inflammatory bowel disease. Am J Gastroenterol. 2024;119(11):2275-2287. doi:10.14309/ajg.0000000000002900 DOI: https://doi.org/10.14309/ajg.0000000000002900

Beaugerie L, Brousse N, Bouvier AM, Colombel JF, Lemann M, Cosnes J, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet. 2009;374(9701):1617-1625. doi:10.1016/S0140-6736(09)61302-7 DOI: https://doi.org/10.1016/S0140-6736(09)61302-7

Lemaitre M, Kirchgesner J, Rudnichi A, Carrat F, Zureik M, Carbonnel F, et al. Association between use of thiopurines or tumor necrosis factor antagonists alone or in combination and risk of lymphoma in patients with inflammatory bowel disease. JAMA. 2017;318(17):1679-1686. doi:10.1001/jama.2017.16071 DOI: https://doi.org/10.1001/jama.2017.16071

Kotlyar DS, Lewis JD, Beaugerie L, Tierney A, Brensinger CM, Gisbert JP, et al. Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis. Clin Gastroenterol Hepatol. 2015;13(5):847-858.e844; quiz e848-850. doi:10.1016/j.cgh.2014.05.015 DOI: https://doi.org/10.1016/j.cgh.2014.05.015

Narous M, Nugent Z, Singh H, Bernstein CN. Risks of melanoma and nonmelanoma skin cancers pre- and post-inflammatory bowel disease diagnosis. Inflamm Bowel Dis. 2023;29(7):1047-1056. doi:10.1093/ibd/izac171 DOI: https://doi.org/10.1093/ibd/izac171

Huang SZ, Liu ZC, Liao WX, Wei JX, Huang XW, Yang C, et al. Risk of skin cancers in thiopurines-treated and thiopurines-untreated patients with inflammatory bowel disease: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2019;34(3):507-516. doi:10.1111/jgh.14533 DOI: https://doi.org/10.1111/jgh.14533

Long MD, Herfarth HH, Pipkin CA, Porter CQ, Sandler RS, Kappelman MD. Increased risk for non-melanoma skin cancer in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2010;8(3):268-274. doi:10.1016/j.cgh.2009.11.024 DOI: https://doi.org/10.1016/j.cgh.2009.11.024

Dugué PA, Rebolj M, Hallas J, Garred P, Lynge E. Risk of cervical cancer in women with autoimmune diseases, in relation with their use of immunosuppressants and screening: population-based cohort study. Int J Cancer. 2015;136(6):E711-E719. doi:10.1002/ijc.29209 DOI: https://doi.org/10.1002/ijc.29209

McKenna MR, Stobaugh DJ, Deepak P. Melanoma and non-melanoma skin cancer in inflammatory bowel disease patients following tumor necrosis factor-α inhibitor monotherapy and in combination with thiopurines: analysis of the Food and Drug Administration Adverse Event Reporting System. J Gastrointestin Liver Dis. 2014;23(3):267-271. doi:10.15403/jgld.2014.1121.233.mrmk DOI: https://doi.org/10.15403/jgld.2014.1121.233.mrmk

Long MD, Martin CF, Pipkin CA, Herfarth HH, Sandler RS, Kappelman MD. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143(2):390-399.e391. doi:10.1053/j.gastro.2012.05.004 DOI: https://doi.org/10.1053/j.gastro.2012.05.004

Muller M, D’Amico F, Bonovas S, Danese S, Peyrin-Biroulet L. TNF inhibitors and risk of malignancy in patients with inflammatory bowel diseases: a systematic review. J Crohns Colitis. 2021;15(5):840-859. doi:10.1093/ecco-jcc/jjaa186 DOI: https://doi.org/10.1093/ecco-jcc/jjaa186

Ytterberg SR, Bhatt DL, Mikuls TR, Koch GG, Fleischmann R, Rivas JL, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386(4):316-326. doi:10.1056/NEJMoa2109927 DOI: https://doi.org/10.1056/NEJMoa2109927

Chaparro M, Baston-Rey I, Fernández-Salgado E, González García J, Ramos L, Diz-Lois Palomares MT, et al. Long-term real-world effectiveness and safety of ustekinumab in Crohn’s disease patients: The SUSTAIN study. Inflamm Bowel Dis. 2022;28(11):1725-1736. doi:10.1093/ibd/izab357 DOI: https://doi.org/10.1093/ibd/izab357

Menter A, Papp KA, Gooderham M, Pariser DM, Augustin M, Kerdel FA, et al. Drug survival of biologic therapy in a large, disease-based registry of patients with psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Eur Acad Dermatol Venereol. 2016;30(7):1148-1158. doi:10.1111/jdv.13611 DOI: https://doi.org/10.1111/jdv.13611

Kridin K, Abdelghaffar M, Mruwat N, Ludwig RJ, Thaçi D. Are interleukin 17 and interleukin 23 inhibitors associated with malignancies?-Insights from an international population-based study. J Eur Acad Dermatol Venereol. 2024;38(2):315-324. doi:10.1111/jdv.19520 DOI: https://doi.org/10.1111/jdv.19520

Card T, Ungaro R, Bhayat F, Blake A, Hantsbarger G, Travis S. Vedolizumab use is not associated with increased malignancy incidence: GEMINI LTS study results and post-marketing data. Aliment Pharmacol Ther. 2020;51(1):149-157. doi:10.1111/apt.15538 DOI: https://doi.org/10.1111/apt.15538

Loftus EV, Jr., Feagan BG, Panaccione R, Colombel JF, Sandborn WJ, Sands BE, et al. Long-term safety of vedolizumab for inflammatory bowel disease. Aliment Pharmacol Ther. 2020;52(8):1353-1365. doi:10.1111/apt.16060 DOI: https://doi.org/10.1111/apt.16060

Puca P, Del Gaudio A, Iaccarino J, Blasi V, Coppola G, Laterza L, et al. Cancer risk in IBD patients treated with JAK inhibitors: reassuring evidence from trials and real-world data. Cancers (Basel). 2025;17(5):735. doi:10.3390/cancers17050735 DOI: https://doi.org/10.3390/cancers17050735

Panaccione R, Lichtenstein G, Colombel JF, Nakase H, Yao X, Klaff J, et al. DOP002 Efficacy and safety of upadacitinib after 4 years of treatment in patients with moderately to severely active ulcerative colitis: interim long-term data from the phase 3 open-label extension study (U-ACTIVATE). Journal of Crohn’s and Colitis. 2025;19(Supplement_1):i84-i86. doi:10.1093/ecco-jcc/jjae190.0041 DOI: https://doi.org/10.1093/ecco-jcc/jjae190.0041

Sandborn WJ, Feagan BG, Hanauer S, Vermeire S, Ghosh S, Liu WJ, et al. Long-term efficacy and safety of ozanimod in moderately to severely active ulcerative colitis: results from the open-label extension of the randomized, Phase 2 TOUCHSTONE study. J Crohns Colitis. 2021;15(7):1120-1129. doi:10.1093/ecco-jcc/jjab012 DOI: https://doi.org/10.1093/ecco-jcc/jjab012

Peyrin-Biroulet L, Dubinsky MC, Sands BE, Panés J, Schreiber S, Reinisch W, et al. Efficacy and safety of etrasimod in patients with moderately to severely active isolated proctitis: results from the Phase 3 ELEVATE UC Clinical Programme. J Crohns Colitis. 2024;18(8):1270-1282. doi:10.1093/ecco-jcc/jjae038 DOI: https://doi.org/10.1093/ecco-jcc/jjae038

Vermeire S, Chiorean M, Panés J, Peyrin-Biroulet L, Zhang J, Sands BE, et al. Long-term safety and efficacy of etrasimod for ulcerative colitis: results from the open-label extension of the OASIS study. J Crohns Colitis. 2021;15(6):950-959. doi:10.1093/ecco-jcc/jjab016 DOI: https://doi.org/10.1093/ecco-jcc/jjab016

Fiorillo C, Schena CA, Quero G, Laterza V, Pugliese D, Privitera G, et al. Challenges in Crohn’s disease management after gastrointestinal cancer diagnosis. Cancers (Basel). 2021;13(3):574. doi:10.3390/cancers13030574 DOI: https://doi.org/10.3390/cancers13030574

Hong SJ, Zenger C, Pecoriello J, Pang A, Vallely M, Hudesman DP, et al. Ustekinumab and vedolizumab are not associated with subsequent cancer in IBD Patients with prior malignancy. Inflamm Bowel Dis. 2022;28(12):1826-1832. doi:10.1093/ibd/izac035 DOI: https://doi.org/10.1093/ibd/izac035

Abu-Sbeih H, Faleck DM, Ricciuti B, Mendelsohn RB, Naqash AR, Cohen JV, et al. Immune checkpoint inhibitor therapy in patients with preexisting inflammatory bowel disease. J Clin Oncol. 2020;38(6):576-583. doi:10.1200/JCO.19.01674 DOI: https://doi.org/10.1200/JCO.19.01674

Gordon H, Biancone L, Fiorino G, Katsanos KH, Kopylov U, Al Sulais E, et al. ECCO guidelines on inflammatory bowel disease and malignancies. J Crohns Colitis. 2023;17(6):827-854. doi:10.1093/ecco-jcc/jjac187 DOI: https://doi.org/10.1093/ecco-jcc/jjac187

Axelrad JE, Hashash JG, Itzkowitz SH. AGA clinical practice update on management of inflammatory bowel disease in patients with malignancy: commentary. Clin Gastroenterol Hepatol. 2024;22(7):1365-1372. doi:10.1016/j.cgh.2024.03.032 DOI: https://doi.org/10.1016/j.cgh.2024.03.032

Herfarth HH, Kappelman MD, Long MD, Isaacs KL. Use of methotrexate in the treatment of inflammatory bowel diseases. Inflamm Bowel Dis. 2016;22(1):224-233. doi:10.1097/MIB.0000000000000589 DOI: https://doi.org/10.1097/MIB.0000000000000589

de Boer NKH, Peyrin-Biroulet L, Jharap B, Sanderson JD, Meijer B, Atreya I, et al. Thiopurines in inflammatory bowel disease: new findings and perspectives. J Crohns Colitis. 2018;12(5):610-620. doi:10.1093/ecco-jcc/jjx181 DOI: https://doi.org/10.1093/ecco-jcc/jjx181

Shelton E, Laharie D, Scott FI, Mamtani R, Lewis JD, Colombel JF, et al. Cancer Recurrence Following Immune-Suppressive Therapies in Patients With Immune-Mediated Diseases: A Systematic Review and Meta-analysis. Gastroenterology. 2016;151(1):97-109.e4. DOI: https://doi.org/10.1053/j.gastro.2016.03.037

Khan N, Patel D, Trivedi C, Kavani H, Medvedeva E, Pernes T, et al. Repeated occurrences of basal cell cancer in patients with inflammatory bowel disease treated with immunosuppressive medications. Am J Gastroenterol. 2020;115(8):1246-1252. doi:10.14309/ajg.0000000000000679 DOI: https://doi.org/10.14309/ajg.0000000000000679

Vedamurthy A, Gangasani N, Ananthakrishnan AN. Vedolizumab or tumor necrosis factor antagonist use and risk of new or recurrent cancer in patients with inflammatory bowel disease with prior malignancy: a retrospective cohort study. Clin Gastroenterol Hepatol. 2022;20(1):88-95. doi:10.1016/j.cgh.2020.10.007 DOI: https://doi.org/10.1016/j.cgh.2020.10.007

Poullenot F, Amiot A, Nachury M, Viennot S, Altwegg R, Bouhnik Y, et al. Comparative risk of incident cancer in patients with inflammatory bowel disease with prior non-digestive malignancy according to immunomodulator: a multicentre cohort study. J Crohns Colitis. 2022;16(10):1523-1530. doi:10.1093/ecco-jcc/jjac061 DOI: https://doi.org/10.1093/ecco-jcc/jjac061

Waljee AK, Higgins PDR, Jensen CB, Villumsen M, Cohen-Mekelburg SA, Wallace BI, et al. Anti-tumour necrosis factor-α therapy and recurrent or new primary cancers in patients with inflammatory bowel disease, rheumatoid arthritis, or psoriasis and previous cancer in Denmark: a nationwide, population-based cohort study. Lancet Gastroenterol Hepatol. 2020;5(3):276-284. doi:10.1016/S2468-1253(19)30362-0 DOI: https://doi.org/10.1016/S2468-1253(19)30362-0

Colombel JF, Sands BE, Rutgeerts P, Sandborn W, Danese S, D’Haens G, et al. The safety of vedolizumab for ulcerative colitis and Crohn’s disease. Gut. 2017;66(5):839-851. doi:10.1136/gutjnl-2015-311079 DOI: https://doi.org/10.1136/gutjnl-2015-311079

D’Haens G, Panaccione R, Baert F, Bossuyt P, Colombel JF, Danese S, et al. Risankizumab as induction therapy for Crohn’s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022;399(10340):2015-2030. doi:10.1016/S0140-6736(22)00467-6 DOI: https://doi.org/10.1016/S0140-6736(22)00467-6

Danese S, Panaccione R, Feagan BG, Afzali A, Rubin DT, Sands BE, et al. Efficacy and safety of 48 weeks of guselkumab for patients with Crohn’s disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial. Lancet Gastroenterol Hepatol. 2024;9(2):133-146. doi:10.1016/S2468-1253(23)00318-7 DOI: https://doi.org/10.1016/S2468-1253(23)00318-7

Hasan B, Tandon KS, Miret R, Khan S, Riaz A, Gonzalez A, et al. Ustekinumab does not increase risk of new or recurrent cancer in inflammatory bowel disease patients with prior malignancy. J Gastroenterol Hepatol. 2022;37(6):1016-1021. doi:10.1111/jgh.15806 DOI: https://doi.org/10.1111/jgh.15806

Beaugerie L, Carrat F, Colombel JF, Bouvier AM, Sokol H, Babouri A, et al. Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer. Gut. 2014;63(9):1416-1423. doi:10.1136/gutjnl-2013-305763 DOI: https://doi.org/10.1136/gutjnl-2013-305763

Itzkowitz SH, Jiang Y, Villagra C, Colombel JF, Sultan K, Lukin DJ, et al. Safety of immunosuppression in a prospective cohort of inflammatory bowel disease patients with a HIstoRy of CancEr: SAPPHIRE Registry. Clin Gastroenterol Hepatol2025;23(5):855-865.e5. doi:10.1016/j.cgh.2024.05.006 DOI: https://doi.org/10.1016/j.cgh.2024.05.006

Gupta A, Peyrin-Biroulet L, Ananthakrishnan AN. Risk of cancer recurrence in patients with immune-mediated diseases with use of immunosuppressive therapies: an updated systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2024;22(3):499-512.e496. doi:10.1016/j.cgh.2023.07.027 DOI: https://doi.org/10.1016/j.cgh.2023.07.027

Penn I. The effect of immunosuppression on pre-existing cancers. Transplantation. 1993;55(4):742-747. doi:10.1097/00007890-199304000-00011 DOI: https://doi.org/10.1097/00007890-199304000-00011

Poullenot F, Laharie D. Management of inflammatory bowel disease in patients with current or past malignancy. Cancers (Basel). 2023;15(4):1083. doi:10.3390/cancers15041083 DOI: https://doi.org/10.3390/cancers15041083

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Kandel R, Murthy SK. Using Immunosuppressive Therapies to Treat Inflammatory Bowel Diseases (IBD) in the Post‑Cancer Setting. Can IBD Today [Internet]. 2025 Jun. 23 [cited 2025 Jul. 19];3(1):13–20. Available from: https://canadianibdtoday.com/article/view/3-1-Kandel_et_al

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