PARIS, France—The risk of developing tuberculosis (TB) is 7 to 17 fold higher among patients receiving anti-TNF monoclonal antibody (mAb) therapy than for those receiving soluble TNF receptors, finds a new study in the July issue of Arthritis & Rheumatism.1

“Our study provides clear evidence of a higher risk of TB with anti-TNF mAb therapy than soluble TNF receptors.”—Florence Tubach, MD, PhD
“Our study provides clear evidence of a higher risk of TB with anti-TNF mAb therapy than soluble TNF receptors,” states lead researcher Florence Tubach, MD, PhD, of Université Paris in France. The increased risk, which was seen early in the course of anti-TNF treatment and in the absence of correct prophylactic antibiotic treatment, favor the reactivation of latent TB over new infection.

TB risk differences reflect different effects on membrane-bound TNF

“These differences [in risk] can be supported by differences in the action of the 2 types of agents on membrane-bound TNF, leading to a differential effect in effector T-cells and Treg cells,” states lead researcher Florence Tubach, MD, PhD, of Université Paris in France. “These different mechanisms of action could also explain a better efficacy of mAb therapy in Crohn’s disease, in other granulomatous diseases such as sarcoidosis and in uveitis.”

Researchers collected data on TB cases among French patients receiving anti-TNF mAb therapy for any indication for 3 years. There were 2 patients treated with anti-TNF agents per case who served as controls. Overall, there were 69 cases of TB seen among patients treated for rheumatoid arthritis, spondylarthritides, inflammatory colitis, psoriasis, and Behçet's disease with infliximab (Remicade®), adalimumab (Humira®), and etanercept (Enbrel®). None of the patients had received the correct chemoprophylactic treatment.

According to the new report, the sex- and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The standardized incidence ratio was 12.2 and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (Enbrel®), the study showed. In the case-control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB. Age, the first year of anti-TNF mAb treatment, and being born in an endemic area were also risk factors for developing active TB, the study showed.

Translating research into practice: Better TB screening warranted

“Our study suggests that taking into account whether patients are born in an endemic area could improve screening for latent TB,” the researchers suggest. Two-thirds of the TB cases in the study occurred in patients with negative skin test results. If the national recommendations for preventive treatment in France were followed many of these patients would have received antibiotic therapy based on the diameter of their tuberculin skin reaction. Such adherence to recommendations could have staved off active TB in many patients.

Going forward, other ways to evaluate latent TB infection may include specific in vitro blood tests for anti-TB cells.

Reference
1. Tubach F, Salmon D, Ravaud P, et al. Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy. Arthritis Rheum. 2009;60:1884-1894.