Cancer Risks and Therapy for IBD

All drugs have risks and benefits, but when there is a small risk of something very serious, like lymphoma, it can be hard to process.

Inflammatory bowel disease, or IBD, includes ulcerative colitis and Crohn's disease. Both are incurable chronic diseases of the intestinal tract. Both have treatments that can reduce surgeries and hospitalizations.

Having IBD and being treated for it is associated with some increased risk of lymphoma, and the risks vary with other factors besides simply being treated.

Inflammatory Bowel Disease

IBD develops due to inflammation in the intestine, which can result in bleeding, fever, elevation of the white blood cell count, as well as diarrhea and cramping abdominal pain.

Abnormalities in IBD are often present in imaging studies such as a CT scan, or a colonoscopy, for instance.

Lymphoma Risk

People with IBD treated with certain therapies -- such as anti-TNF agents and immune modifiers -- are at increased risk for some cancers that involve the lymphocyte white blood cells, according to several studies. There is some uncertainty about how much risk there is, however.

Lymphoma is a cancer that starts in lymphocyte white blood cells, which are part of the body’s immune system. The two main categories of lymphoma are Hodgkin and non-Hodgkin lymphoma, or NHL. There are numerous types and subtypes. It’s been observed that NHL occurs at higher than the expected rates in a number of different diseases that require immune suppression, such as IBD.

The risks of lymphoma are not the same for everybody who has IBD. Risks vary according to factors such as age, gender, and other individual factors.

Evaluating the risks and benefits of IBD therapies with your doctor is an important part of the treatment decision. Often, it is decided that the substantial benefit of these therapies outweighs the very small risk that is incurred.

IBD Treatments

Using anti-inflammatory medication for IBD to induce remission followed by maintenance therapy with immunosuppressant medications is still the main approach to therapy.

Thiopurines -- such as azathioprine -- are widely used in the therapy of chronic active inflammatory bowel disease.

In patients with IBD treated with thiopurines, there is an increased risk of some types of blood cancer, but the number of cancers that develop as a result of treatment is believed to be very small. In people who get organ transplants, NHL associated with immune suppression is called post-transplant lymphoproliferative disorder, and some of what is known about lymphoma risk comes from this group of patients.

Particular patterns of lymphoma have been seen with immune-modifying agents used in IBD. Lymphoma after the transplant is one of them. Lymphoma after having mononucleosis, or mono, is a possibility, and this form tends to affect men younger than 35 years. Rarely, hepatosplenic T-cell lymphoma may develop, and it tends to develop after at least 2 years of therapy with a combination of thiopurines and anti-tumor necrosis factor treatment, or thiopurines alone.

  • Azathioprine was associated with a 2.40 x increased lymphoma risk in a study published in the “American Journal of Epidemiology.”
  • The combination of azathioprine and 6-mercaptopurine has a 4.92 fold elevated risk for lymphoma development among people with IBD, according to a study published in “Clinical Gastroenterology and Hepatology.”

Much less is known about methotrexate and lymphoma risk in IBD. With anti-TNF agents, a 2009 study found that the risk of lymphoma with anti-TNF + immunomodulator was greater than immunomodulator alone.

Bottom Line

There are many unanswered questions about lymphoma risk in the context of IBD therapy. If you have IBD and need therapy, it is best to discuss any concerns you may have about the risks with your doctor, who can help put things in perspective and help tailor the facts and figures to your particular situation.

Without appropriate treatment, patients with Crohn's disease and ulcerative colitis can have a greatly diminished quality of life. Some doctors highlight the fact that we are probably dealing with a very small number of extra cases of lymphoma among thousands of patients and many years that leads us to make conclusions about risk.

One thing is certain: excessive worry and chronic stress are associated with all kinds of health problems, so if your and your doctor have decided that you need treatment, it doesn't do you any good to worry.

Sources

Pasternak B, Svanstrom H, Schmiegelow K, et al. Use of Azathioprine and the Risk of Cancer in Inflammatory Bowel Disease. Am. J. Epidemiol. 2013;177(11): 1296-1305.

Kotlyar DS, Lewis JD, Beaugerie L, 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.e4.

Bär F, Sina C, Fellermann K. Thiopurines in inflammatory bowel disease revisited. World J Gastroenterol. 2013;19(11):1699-1706.

Sokol H, Beaugerie L. Inflammatory bowel disease and lymphoproliferative disorders: the dust is starting to settle. Gut. 2009 Oct;58(10):1427-36.

Kandiel A, Fraser AG, Korelitz BI, Brensinger C, Lewis JD. Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut. 2005;54(8):1121-1125.

Askling J, Brandt L, Lapidus A, et al. Risk of haematopoietic cancer in patients with inflammatory bowel disease. Gut. 2005;54(5):617-622.

Bhandari BM, Kroser JA, Bloomfeld RS, Lynch SP. Inflammatory Bowel Disease. American College of Gastroenterology. 2013.

Siegel CA. Risk of Lymphoma in Inflammatory Bowel Disease. Gastroenterol Hepatol. 2009;5(11):784-790.

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