Anti-Tumor Necrosis Factor (TNF) Agents
November 4, 2011
In April 2011, FDA warned the public of the potential risk of hepatosplenic T-cell lymphoma (HSTCL) in patients treated with anti-TNF agents, azathioprine, or mercaptopurine. An association between anti-TNF agents and several types of cancer, including HSTCL, was originally reported by FDA in June 2008. In August 2009, FDA reported several malignancies, including 10 cases of HSTCL, in an ongoing safety analysis of anti-TNF agents. All cases of HSTCL in the 2009 report were in children or adolescents with inflammatory bowel disease (ie, ulcerative colitis or Crohn disease), treated with an anti-TNF agent in combination with either azathioprine or mercaptopurine. FDA has now documented 43 distinct cases of HSTCL in patients using anti-TNF agents, azathioprine, or mercaptopurine, as combination therapy or monotherapy. Most of these cases occurred in patients with ulcerative colitis or Crohn disease, but patients with psoriasis or rheumatoid arthritis have also developed HSTCL. Patients ranged in age from 12 to 74 years. Labeling for the anti-TNF agents already contains warnings about malignancy risk as a result of the 2008 FDA findings. Labeling for azathioprine and mercaptopurine will be updated to include specific warnings about HSTCL.
Hepatosplenic T-cell lymphoma is an aggressive cancer of the white blood cells that is usually fatal. Signs and symptoms of HSTCL may include abdominal pain, hepatomegaly, night sweats, persistent fever, splenomegaly, or weight loss. Monitor closely for signs or symptoms of malignancy. FDA recommends carefully balancing the risks and benefits of treatment with these agents particularly in those patients with inflammatory bowel disease.
FDA is encouraging healthcare providers to continue to report malignancies occurring in patients treated with anti-TNF agents. Reports should include de-identified patient demographic information, risk factors for malignancy, concurrent or past immunosuppressant exposure, anti-TNF agent indication, dose, and duration, and date of malignancy diagnosis and outcome.
More information is available at the following links:
- MedWatch Alert April 14, 2011; Updated November 4, 2011:
- FDA Safety Communication April 14, 2011:
- FDA Questions and Answers August 25, 2009:
- MedWatch Alert August 7, 2009:
- Information for Healthcare Professionals August 4, 2009:
- MedWatch Alert June 4, 2008:
- Early Communication About Ongoing Safety Review: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ DrugSafetyInformationforHeathcareProfessionals/ucm070725.htm
November 4, 2011; April 15, 2011; University of Utah, Drug Information Service. Copyright 2011, Drug Information Service, University of Utah, Salt Lake City, UT.