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FDA Drug Safety Podcast for Healthcare Professionals: Safety Review update on reports of Hepatosplenic T-Cell Lymphoma in adolescents and young adults receiving tumor necrosis factor (TNF) blockers, azathioprine and/or mercaptopurine

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Welcome, my name is Catherine Chew, a pharmacist in the Division of Drug Information. On April, 14, 2011, the Food and Drug Administration issued a Drug Safety Communication 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). This is primarily in adolescents and young adults being treated for Crohn's disease and ulcerative colitis with medicines known as tumor necrosis factor, or TNF, blockers, as well as 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 may also occur. Children with the disease may have growth problems, develop intestinal blockage, and experience malnutrition. HSTCL is an aggressive 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 is updating the public about the number of reported cases of HSTCL. From initiation of TNF blocker marketing to December 31, 2010, the following HSTCL cases have been identified in the Adverse Event Reporting System database, the literature, and the HSTCL Cancer Survivors' Network in association with the following agents: 20 with Infliximab, 1 with etanercept, 2 with adalimumab, 5 with the combination of infliximab and adalimumab, none with certolizumab, none with golimumab, 12 with azathioprine, and 3 with mercaptopurine. Of note, in the 20 cases identified with infliximab use, 18 of the patients were also using concomitant mercaptopurine or azathioprine. For the remaining two patients, concomitant drug use was not reported. Of the 5 cases identified with the combination of infliximab and 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 or co-factor. A complete list of cumulative cases associated with selected immunosuppressant use reported as of December 31, 2010 can be found in the Drug Safety Communication on our website.

Due to the potential increased risk for cancers, including HSTCL, the risks and benefits of using TNF blocker products, azathioprine and/or mercaptopurine should be carefully weighed when prescribing these drugs especially in adolescents and young adults.

FDA will continue to communicate any new safety information to the public as it becomes available.

At this time, FDA recommends that Healthcare Professionals:

  1. Discuss with patients and caregivers the increased risk of developing HSTCL, especially in adolescents and young adults, taking into account the risks and benefits of TNF blockers, azathioprine, and/or mercaptopurine, and other immunosuppressive therapies.
  2. Educate patients and caregivers about the signs and symptoms of malignancies such as HSTCL so that they are aware of and can seek evaluation and treatment of any signs or symptoms. These may include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.
  3. Monitor for the emergence of malignancies when a patient has been treated with TNF blockers, azathioprine, and/or mercaptopurine.
  4. Know that people with rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis may be more likely to develop lymphoma than the general U.S. population. Therefore, it may be difficult to measure the added risk of TNF blockers, azathioprine, and/or mercaptopurine.
  5. Report adverse events involving TNF blockers, azathioprine and/or mercaptopurine to the FDA MedWatch program at www.fda.gov/medwatch.

Thank you for listening. The FDA is committed to keeping healthcare professionals informed of the latest safety information. To learn more about this Drug Safety Communication, go to www.fda.gov/Drugs. If you have any drug questions, you can reach us at druginfo@fda.hhs.gov.

 

 

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