TNF Blockers and Cancer: FDA Requires Increased Surveillance

Emma Hitt, PhD


November 03, 2011

November 3, 2011 (UPDATED November 4, 2011) — The US Food and Drug Administration (FDA) announced today that it is requiring the manufacturers of tumor necrosis factor (TNF)-α blockers to perform enhanced safety surveillance of these drugs because of the potential risk for cancer in children and adults aged 30 years or younger.

Manufacturers will be required to submit reports of all malignancies and, in the case of malignancy in pediatric and young adult patients, expedited reports (provided within 15 days).

"This type of safety surveillance is important for our improved understanding of malignancies in pediatric and young adult patients treated with TNF blockers because it will allow FDA to more completely capture and analyze all reported malignancies based on more complete and consistent reports," the FDA states in an alert sent today from the Division of Drug Information of the FDA's Center for Drug Evaluation and Research'.

The FDA recommends that healthcare professionals "remain vigilant" for TNF blocker–related malignancies and report them to the FDA's MedWatch program or to the manufacturer. They add that "healthcare professionals may be queried by FDA or the manufacturer for additional clinical and diagnostic information related to the malignancy cases."

On November 4, 2011, MedWatch, the FDA's safety information and adverse event reporting program, sent out a new alert asking healthcare professionals to include specific information in its reports of malignancy in patients treated with TNF blockers. This information includes:

  • patient characteristics (age, sex, no patient identifiers);

  • risk factors for malignancy;

  • exposure to other immune-suppressing products or products with risk for malignancy;

  • indication for TNF blocker treatment;

  • TNF blocker exposure (duration, dose);

  • cancer diagnosis (date of diagnosis, stage);

  • biopsy results; and

  • outcomes of malignancy (treatments, event outcome)

The FDA first warned of the increased risk for childhood and adolescent cancers associated with TNF blockers in 2008, and warnings were added to the product labels of these drugs in 2009.

Today's announcement comes in the wake of several somewhat conflicting findings about TNF blockers and cancer risk.

One report in the August 2010 issue of Arthritis & Rheumatism found that children treated with TNF-α blockers may have increased cancer risk but that cancer cases reported in these children were confounded by underlying illnesses and concomitant use of immunosuppressants.

Likewise, another report found that TNF inhibitors used to treat rheumatoid arthritis (RA) may increase the risk for skin cancer (including melanoma) but did not appear to be associated with increased risk for other malignancies. The pooled analysis, published in the September 1, 2011, issue of the Annals of the Rheumatic Diseases, found negligible increase or no increase in overall risk of developing any cancer.

However, several studies have demonstrated an increased risk with these agents. In the August 2011 issue of Rheumatology, a study including data from over 20,000 US military veterans showed that nonmelanoma skin cancer risk is about one third higher for patients with RA treated with TNF inhibitors than for similar patients treated with nonbiologic disease-modifying antirheumatic drugs.

In addition, in April of this year, the FDA reported an association between hepatosplenic T-cell lymphoma in adolescents and young adults treated with TNF blockers, azathioprine, and/or mercaptopurine.

Drugs included in the TNF blocker class include infliximab (Remicade, Centocor), etanercept (Enbrel, Amgen and Pfizer), adalimumab (Humira, Abbott Laboratories), certolizumab pegol (Cimzia, UCB), and golimumab (Simponi, Centocor Ortho Biotech Inc).

Even in the absence of immunosuppressive drugs, a higher incidence of lymphomas has been found in patients being treated for RA, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.

More information about the announcement is available on the FDA Web site and on the MedWatch Web site.

Adverse events related to use of TNF blockers should be communicated to the MedWatch by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.


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