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Treatment with anti-TNF ( tumor necrosis factor ) blockers is recognized as a risk factor for tuberculosis ( TB ) in patients with immune-mediated inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, psoriatic arthritis and psoriasis. Most tuberculosis cases develop as a result of reactivation of a latent TB infection, and health authorities worldwide recommend screening for latent tuberculosis and treating patients before initiating anti-TNF treatment.

A new study examined cases of tuberculosis associated with anti-TNF therapy and found that the risk of tuberculosis is higher for patients receiving anti-TNF monoclonal antibody therapy [ Infliximab ( Remicade ) or Adalimumab ( Humira ) ] than for those receiving soluble TNF receptor therapy [ Etanercept ( Enbrel ) ].

Led by Xavier Mariette of the Université Paris-Sud, researchers set up a national registry in France to collect all cases of tuberculosis occurring during a three-year period in patients receiving anti-TNF therapy for any reason. Researchers collected data on 69 cases of tuberculosis, assessing risk factors for tuberculosis before anti-TNF therapy began and anti-TNF treatment history.

The results showed that the risk of tuberculosis for patients receiving anti-TNF therapy compared with the French population differed depending on the anti-TNF agent used; those receiving monoclonal anti-TNF therapy had a higher risk than those receiving sTNFR therapy. The risk of tuberculosis was higher during the first year of anti-TNF treatment, which enhanced the reactivation of latent tuberculosis. Two thirds of tuberculosis cases occurred in patients with negative skin tests.

The Authors noted that other countries have set up registries to investigate the safety of anti-TNF agents, but TB rates were so low that it was difficult to discern a difference in risk between the different types of anti-TNF agents; the current study, however, clearly demonstrates this difference. This study examined tuberculosis cases in the entire French population and researchers were therefore able to collect many more cases. In addition, it is the only registry to collect safety data for patients receiving anti-TNF therapy for any indication.

The mechanism by which TNF antagonists reactivate latent tuberculosis is not fully understood, but the authors suggest that differences in the action of the two types of anti-TNF agents in specific T helper cells ( which play an important role in maximizing the capabilities of the immune system ) and T regulatory cells ( which suppress activation of the immune system ) may help explain the differences in the risk of tuberculosis that were observed. The Authors conclude that the differences seen with the two types of anti-TNF treatment may also explain the better efficacy of monoclonal antibody therapy in certain diseases, such as Crohn's disease, sarcoidosis and uveitis.

Source: Arthritis & Rheumatism, 2009


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