From the Guidelines
Thiopurines are the primary IBD medications that increase cancer risk, particularly for non-melanoma skin cancers, nonintestinal lymphoma, and genitourinary cancer. Several studies have demonstrated this association, with a recent commentary published in Clinical Gastroenterology and Hepatology in 2024 1 highlighting the increased risk of these cancers in patients with IBD treated with thiopurines. The risk of non-melanoma skin cancer is almost 2-fold higher in patients treated with thiopurines, and ongoing use may increase the risk of recurrent skin cancer.
Key points to consider include:
- The risk of nonintestinal lymphoma is also higher in patients treated with thiopurines, with a standardized incidence ratio ranging from 2.8 to 9.2 compared to those not exposed to thiopurines 1.
- Genitourinary cancer, particularly urinary tract cancers, is associated with thiopurine use, with a 2.8-times higher risk in males 1.
- The combination of thiopurines with anti-TNF agents may further increase the risk of certain cancers, such as hepatosplenic T-cell lymphoma, which is often fatal 1.
- Patients on thiopurines should undergo regular dermatologic examinations and be vigilant about sun protection to mitigate the risk of skin cancer.
The benefits of thiopurines in managing IBD often outweigh the potential cancer risks, but patients should be aware of these risks and take steps to minimize them. Regular monitoring and sun protection are essential for patients on thiopurines, particularly those with a history of skin cancer or prolonged use of these medications.
From the FDA Drug Label
Mercaptopurine is mutagenic in animals and humans, carcinogenic in animals, and may increase the patient's risk of neoplasia. Cases of hepatosplenic T-cell lymphoma have been reported in patients treated with mercaptopurine for inflammatory bowel disease. Mercaptopurine is immunosuppressive and may impair the immune response to infectious agents or vaccines. Patients receiving immunosuppressive therapy, including mercaptopurine, are at an increased risk of developing lymphoproliferative disorders and other malignancies, notably skin cancers (melanoma and non-melanoma), sarcomas (Kaposi's and non-Kaposi's) and uterine cervical cancer in situ.
IBD medications that increase cancer risk:
- Mercaptopurine 2
The incidence of malignancies, including invasive cervical cancer and lymphoma, was greater in TNF blocker treated patients than in controls. Due to the risk of HSTCL carefully assess the risk/benefit especially if the patient has Crohn's disease or ulcerative colitis, is male, and is receiving azathioprine or 6-mercaptopurine treatment.
- Infliximab, a TNF blocker, may also increase the risk of cancer, particularly in patients with Crohn's disease or ulcerative colitis who are receiving azathioprine or 6-mercaptopurine treatment 3
From the Research
IBD Medications and Cancer Risk
- Thiopurines, such as azathioprine and mercaptopurine, increase the relative risk for skin, urinary tract, and lymphoid tissue malignancies, although the absolute risk is low 4
- The use of thiopurines is generally avoided in patients over the age of 65 years due to the increased risk of malignancies 4
- Methotrexate has a better safety profile relating to malignancies compared to thiopurines, but its use is often reserved as a second-line therapy 4
- Biologic therapies, such as infliximab, may increase the risk of malignancies, particularly lymphoma, although the data does not provide clear evidence for a causal association 5
- Immunosuppressive drugs, including thiopurines and tumor necrosis factor antagonists, increase the risk of infections and cancers, with the nature and magnitude of the risks varying with drug class and patient characteristics 6
Patient-Specific Risk Assessment
- The decision to use immunosuppressive drugs should be based on a clear explanation of treatment risks and integration of the patient's emotional perception of risks 6
- Models to assess the benefit:risk ratio of long-term use of immunosuppressive drugs should be adapted based on patients' age, sex, and IBD phenotype 6
- Patients with IBD should be informed of the potential risks of their medications, including the risk of cancer, and should be involved in the decision-making process 7
Management of IBD Medications
- Patients with IBD who do not have COVID-19 should continue their prescribed IBD therapies, although steroids should be weaned when possible 8
- Patients with IBD who test positive for COVID-19 should hold biologics, thiopurines, methotrexate, and tofacitinib for at least 2 weeks, and those who have symptoms should not restart these medications until symptom resolution 8