TNF Blockers and Risk of Infection

Is Risk of Infection Increased With Use of a TNF Blocker?

What is the relationship between TNF (tumor necrosis factor) and infection? Is there any case in which a patient's medical history or clinical symptoms would preclude prescribing TNF blockers? Also, is there any time when these drugs should be discontinued or even temporarily discontinued, such as if a patient has a cold, flu, infection, or upcoming surgery?

Nurse setting up an IV bag

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Side Effects of TNF Blockers

TNF blockers are a very effective treatment for rheumatoid arthritis. Like all medications, however, there are potential side effects.

In particular, the five TNF blockers—Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab), Simponi (golimumab), and Cimzia (certolizumab pegol)—increase the risk for development of tuberculosis (TB). The reason this occurs is that tumor necrosis factor (TNF) plays a crucial role in the body's immune defense against the mycobacteria that cause TB.

As a result, it is recommended that doctors screen patients with a TB skin test prior to starting treatment with a TNF blocker. If there is evidence of prior exposure (a raised red area will develop within two to three days at the site of the skin test), a medication can be given in combination with the TNF blocker to allow treatment.

In addition, there is evidence from clinical studies as well as post-marketing reports (reports from patients and doctors who used the drugs after they were approved by the FDA) that TNF blockers increase the risk of other serious infections (in addition to tuberculosis) in those using them compared to the general population.


Despite good clinical outcomes in people with rheumatoid arthritis, concerns remain because, typically, the healthiest patients are entered into clinical studies, and many cases of infection are not reported once the drug is on the market. Here's the bottom line:

  • It is recommended that TNF blockers not be started by someone who has an active infection.
  • Patients who have serious recurrent infections or chronic infections should avoid using TNF blockers.
  • Furthermore, TNF blockers should be temporarily discontinued in those patients who develop a serious infection while using a TNF blocker or those who require antibiotics to treat their infection.

Scott J. Zashin, M.D. said, "Whether to discontinue therapy in patients with minor infections is unclear, but I typically recommend avoiding treatment, as I do not feel the benefits of continuing treatment during infection outweigh the risks. With elective surgery, there are no recommendations from the companies as to whether to temporarily stop treatment. There is limited and conflicting data on the effect of TNF blockers on surgical outcomes. In most cases, I recommend stopping Enbrel 1-2 weeks before surgery, and resume 1 week later, if there are no signs or symptoms of infection. Humira should be stopped 2 weeks before and resumed 1 week after. Remicade should be stopped 4 weeks before and resumed 10 days to 4 weeks after surgery."

Note: Please consult your physician for advice on whether you must temporarily stop Enbrel, Humira, Remicade, Simponi, or Cimzia prior to surgery. Individual physicians may have different requirements.

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  • Scott J. Zashin, M.D., clinical assistant professor at University of Texas Southwestern Medical School, phone interview.

By Carol Eustice
Carol Eustice is a writer covering arthritis and chronic illness, who herself has been diagnosed with both rheumatoid arthritis and osteoarthritis.