The U.S. Food and Drug Administration (FDA) is informing the public that it continues to receive reports of a rare cancer of white blood cells (known as hepatosplenic T-Cell lymphoma or HSTCL), primarily in adolescents and young adults being treated for Crohn’s disease and ulcerative colitis with medicines known as tumor necrosis factor (TNF) blockers, as well as with azathioprine, and/or mercaptopurine.
Crohn's disease and ulcerative colitis cause inflammation of the digestive system. Common symptoms are pain in the abdomen, cramps, and diarrhea. Bleeding from the rectum, weight loss, joint pain, skin problems and fever also may occur. Children with the disease may have growth problems, develop intestinal blockage, and experience malnutrition.
Facts about TNF Blockers, Azathioprine, and Mercaptopurine
- TNF blockers suppress the immune system by blocking the activity of TNF, a substance in the body that can cause inflammation and lead to immune-system diseases, such as Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis. The drugs in this class include Remicade (infliximab), Enbrel (etanercept), Humira (adalimumab), Cimzia (certolizumab pegol) and Simponi (golimumab).
- Azathioprine (also known as Imuran) and mercaptopurine (known as Purinethol) also suppress the immune system. They are commonly used as part of a combination regimen or used alone to treat Crohn’s disease and ulcerative colitis, although they are not approved for those uses.
- Azathioprine is approved for the prevention of rejection following renal transplantation and for the reduction of signs and symptoms of rheumatoid arthritis.
- Mercaptopurine is approved to treat acute lymphatic leukemia.
HSTCL is an aggressive (fast-growing) cancer and is usually fatal. The majority of cases reported were in patients being treated for Crohn’s disease or ulcerative colitis, but also included a patient being treated for psoriasis and two patients being treated for rheumatoid arthritis. FDA is now updating the number of reported cases of HSTCL.
Although most reported cases of HSTCL occurred in patients treated with a combination of medicines known to suppress the immune system, including the TNF blockers, azathioprine, and/or mercaptopurine, there have been cases reported in patients receiving azathioprine or mercaptopurine alone.
FDA believes the risks and benefits of using TNF blockers, azathioprine, and/or mercaptopurine should be carefully weighed when prescribing these drugs to children and young adults, especially for the treatment of Crohn’s disease and ulcerative colitis. Patients should continue to talk to their Healthcare Professionals about the potential risk of HSTCL with use of these medications in order to make the best decision about their medical treatment.
FDA previously communicated about the increased risk of lymphomas and other cancers associated with the use of TNF blockers in children and adolescents in June 2008 and in August 2009 when warnings were added to the TNF blocker labels.
The product labels for Remicade (infliximab) and Humira (adalimumab) have been updated and the product labels for azathioprine and mercaptopurine are being updated to include warnings about HSTCL that have been reported in patients treated with these products.
FDA will continue to communicate any new safety information to the public as it becomes available.
Additional Information for Patients
- • Be aware that taking TNF blockers, azathioprine, and/or mercaptopurine may increase the risk of HSTCL.
- • Review the Medication Guide that accompanies a prescription for TNF blockers.
- • Do not stop taking TNF blockers, azathioprine, and/or mercaptopurine without talking to your healthcare professional.
- • Discuss any questions or concerns about these medications with your healthcare professional
Data Summary
FDA is updating the public about the number of reported cases of Hepatosplenic T-cell Lymphoma (HSTCL). From initiation of TNF blocker marketing to December 31, 2010, the following HSTCL cases have been identified in the Adverse Event Reporting System (AERS) database (de-duplicated), the literature, and the HSTCL Cancer Survivors' Network in association with the following agents (mutually exclusive): Infliximab (20), etanercept (1), adalimumab (2), infliximab/adalimumab (5), certolizumab (0), golimumab (0), azathioprine (12), and mercaptopurine (3). Of note, in the 20 cases identified with infliximab use, 18 of the patients also were using concomitant mercaptopurine or azathioprine (for the remaining two patients, concomitant drug use was not reported). Of the 5 cases identified with infliximab/adalimumab use, 4 patients were using concomitant mercaptopurine or azathioprine (for the remaining patient, concomitant drug use was not reported). Complete medical histories have not been obtained on some cases to exclude a history of exposure to a potential confounder/co-factor.
