Why is there an increased risk of infection which occurs with the TNF blockers (Enbrel, Remicade, and Humira)? What is the relationship between TNF and infection? Is there any patient medical history or clinical symptoms which would preclude prescribing TNF blockers? Also, is there any time when these drugs should be discontinued or even temporarily discontinued (if a patient has a cold, flu, infection, or upcoming surgery)?
The three TNF blockers: Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab), 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 bacteria causing this illness.
As a result, it is recommended that doctors screen patients with a TB skin test prior to starting these medications. If there is evidence of prior exposure, (a raised red area will develop within 2-3 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 took the drugs after approval by the FDA) that The TNF blockers increase the risk of serious infections (in addition to tuberculosis) compared to the general population.
On the other hand, there is no evidence that they increase the risk of serious infection compared to a similar group of rheumatoid arthritis patients. Despite good clinical outcomes in the rheumatoid group, there is still concern that these drugs actually do increase the risk of serious infection 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.
Whether or not to discontinue therapy in patients with minor infections is unclear but I typically will recommend avoiding treatment as I do not feel the benefits of continuing treatment during infection outweighs the risks. With elective surgery, there are no recommendations from the companies as to whether or not to temporarily stop treament. There is limited and conflicting data on the effect of TNF blockers on surgical outcomes. In most cases, I (Dr. Zashin) recommend stopping Enbrel 1-2 weeks before surgery, and resume 1 week later if there are no signs or symptoms of infections. Humira stop 2 weeks before and resume 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, or Remicade prior to surgery. Physicians may have different requirements.)
Answer provided by Scott J. Zashin, M.D., clinical assistant professor at University of Texas Southwestern Medical School, Division of Rheumatology, in Dallas, Texas. Dr. Zashin is also an attending physician at Presbyterian Hospitals of Dallas and Plano. He is a fellow of the American College of Physicians and the American College of Rheumatology and a member of the American Medical Association. Dr. Zashin is author of Arthritis Without Pain - The Miracle Of Anti-TNF Blockers. The book is a must-have for anyone on one of the biologic drugs (Enbrel, Remicade, Humira) or considering the biologic drugs. Read Carol Eustice's review of the book.
