DNC News

Anti-Tumor Necrosis Factor Drugs: Are they worth the risk?

January 5, 2006

Jacob Schor, ND


Last summer in a newsletter that was mostly about my favorite mosquito repellent, I strayed into a discussing Tumor Necrosis Factor (TNF) and West Nile Virus (WNV). Tumor Necrosis Factor is an important element in defending the body against WNV. There are several drugs on the market that stop TNF activity and these may, as I wrote, “…..make a West Nile Virus infection worse. People taking these medications are at greater risk of injury or death from WNV infections. [i] These drugs include: monoclonal antibodies, such as infliximab (Remicade®) or adalimumab (Humira®); or circulating receptor fusion proteins such as etanercept (Enbrel®). These drugs are used to treat various autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease and psoriasis.”


Within day of my sending out that newsletter, one of Denver 's eminent rheumatologists wrote defending the use of these medications, arguing that no instances of severe WNV infection were seen in drug trials. As WNV is a new to this part of the world and still rarely seen, the absence of severe WNV infections in the trials did not exculpate these medications to my thinking.


It turns out that several months before our correspondence, a study had been published that put these drugs in a far worse light than my little worries about West Nile Virus. Tumor Necrosis Factor's primary function, as one should guess from the name, is to kill tumor cells. In the May 17 issue of the Journal of the American Medical Association (JAMA), Bongartz et al. from the Mayo Clinic, published a meta-analysis of data collected from the various trials using anti- TNF drugs in treating rheumatoid arthritis. They looked at the risk of serious infections and malignancies with troubling results.

[ JAMA. 2006 May 17;295(19):2275-85. ]


Data was collected from nine randomized, controlled trials that compared either of the anti-TNF antibody drugs, adalimumab or infliximab, against a placebo. The trials had to last at least 12 weeks. This combined analysis had a total of 3,493 patients treated with the anti-TNF drugs and 1,512 patients who received placebo. With this pooled data, the researchers had a large enough group of patients to look for two outcomes that were difficult to prove in smaller studies. They measured increased incidence of serious infections and malignancy in patients given the drugs. Their results were not pretty.


The risk of getting cancer was 3.3 times higher in people taking the drugs compared to those taking a placebo. That translates into one person in 154 got cancer in a 6-12 month period of treatment who wouldn't have gotten it without the drug. For serious infections, the numbers are worse. One in 59 patients developed a serious infection in a period of 3–12 months who wouldn't have without the drug. [ii] Keep in mind that these drugs are not short term. Doctors prescribe these drugs to treat chronic diseases and patients use them for years. Assume that the risk of cancer or infection will only increase the longer the drugs are used. The authors showed that the increased risks were dose dependent, the more drug a patient took, the better their chance of getting cancer or infection. This fact should silence the skeptics.

Autoimmune diseases of the sorts these dugs are prescribed for are common. Our experience is that they often respond well to naturopathic treatment. Simple things like diet changes, vitamins and herbs may adequately control them. To this simple practitioner of naturopathy, it would seem that prescribing Anti-TNF drugs, with both theoretical and proven risks associated with their use, somehow overlooks that Hippocratic injunction to, “First, Do no harm.”



Last July's mosquito repellent article is posted at: http://denvernaturopathic.com/news/westnile.html






J Rheumatol. 2006 Jan;33(1):191-2. Epub 2005 Dec 1.


West nile virus meningoencephalitis and acute flaccid paralysis after infliximab treatment.

Chan-Tack KM , Forrest G .

Institute of Human Virology and the Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. kchan@medicine.umaryland.edu

West Nile virus (WNV) can cause severe central nervous system (CNS) illnesses including meningoencephalitis (MNE) and acute flaccid paralysis (AFP). Risk factors include advanced age, immunosuppression, cancer, and diabetes. In vitro studies show that tumor necrosis factor (TNF) has anti-WNV activity and is protective against WNV infection. Anti-TNF-a monoclonal antibodies may increase susceptibility to WNV by inhibiting an adequate TNF-a response, leading to prolonged viremia, viral penetration into the CNS, and fulminant WNV-CNS disease. We describe a fatal case of WNV with MNE and AFP after infliximab therapy. During WNV outbreaks, clinicians should encourage patients receiving anti-TNF-a drugs to take appropriate preventive measures because of the risk of severe WNV-CNS disease



JAMA. 2006 May 17;295(19):2275-85.

Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials.

Bongartz T , Sutton AJ , Sweeting MJ , Buchan I , Matteson EL , Montori V .

Division of Rheumatology and Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA. bongartz.tim@mayo.edu

CONTEXT: Tumor necrosis factor (TNF) plays an important role in host defense and tumor growth control. Therefore, anti-TNF antibody therapies may increase the risk of serious infections and malignancies. OBJECTIVE: To assess the extent to which anti-TNF antibody therapies may increase the risk of serious infections and malignancies in patients with rheumatoid arthritis by performing a meta-analysis to derive estimates of sparse harmful events occurring in randomized trials of anti-TNF therapy. DATA SOURCES: A systematic literature search of EMBASE, MEDLINE, Cochrane Library, and electronic abstract databases of the annual scientific meetings of both the European League Against Rheumatism and the American College of Rheumatology was conducted through December 2005. This search was complemented with interviews of the manufacturers of the 2 licensed anti-TNF antibodies. STUDY SELECTION: We included randomized, placebo-controlled trials of the 2 licensed anti-TNF antibodies (infliximab and adalimumab) used for 12 weeks or more in patients with rheumatoid arthritis. Nine trials met our inclusion criteria, including 3493 patients who received anti-TNF antibody treatment and 1512 patients who received placebo. DATA EXTRACTION: Data on study characteristics to assess study quality and intention-to-treat data for serious infections and malignancies were abstracted. Published information from the trials was supplemented by direct contact between principal investigators and industry sponsors. DATA SYNTHESIS: We calculated a pooled odds ratio (Mantel-Haenszel methods with a continuity correction designed for sparse data) for malignancies and serious infections (infection that requires antimicrobial therapy and/or hospitalization) in anti-TNF-treated patients vs placebo patients. We estimated effects for high and low doses separately. The pooled odds ratio for malignancy was 3.3 (95% confidence interval [CI], 1.2-9.1) and for serious infection was 2.0 (95% CI, 1.3-3.1). Malignancies were significantly more common in patients treated with higher doses compared with patients who received lower doses of anti-TNF antibodies. For patients treated with anti-TNF antibodies in the included trials, the number needed to harm was 154 (95% CI, 91-500) for 1 additional malignancy within a treatment period of 6 to 12 months. For serious infections, the number needed to harm was 59 (95% CI, 39-125) within a treatment period of 3 to 12 months. CONCLUSIONS: There is evidence of an increased risk of serious infections and a dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy. The formal meta-analysis with pooled sparse adverse events data from randomized controlled trials serves as a tool to assess harmful drug effects.


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