BOSTON – The risk of Legionnaires’ disease associated with tumor necrosis factor-alpha antagonist therapy is greatest during the first year of treatment and is significantly higher for patients receiving adalimumab or infliximab, compared with etanercept, according to a study reported Sept. 15 at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
Using data from the prospective French RATIO (Research Axed on Tolerance of Biotherapies) registry, which was designed to collect information on opportunistic and severe bacterial infections and lymphoma in patients treated with anti–tumor necrosis factor–alpha (anti-TNF-alpha) agents, Dr. Fanny Lanternier of the Necker Hospital for Sick Children in Paris and colleagues conducted an incidence and risk factor study to investigate the relationship between the three drugs included in the registry – adalimumab, infliximab, and etanercept – and Legionella pneumophila infection, which they previously reported in patients receiving anti-TNF–alpha treatment. The researchers used the French population as the reference for the incidence analysis and they conducted a case control study – with four anti-TNF-alpha–treated controls per case – to investigate the risk of newly diagnosed cases of L. pneumophila infection. The mean patient age was 53 years.
From Feb. 1, 2004, to Jan.1, 2007, the RATIO registry received reports of 27 cases of laboratory-confirmed L. pneumophila infection. “The overall annual incidence rate of infection for patients on anti-TNF–alpha therapy, adjusted for age and sex, was 47/100,000 patients per year, which represents a 13-fold increased risk, compared with the reference population,” Dr. Lanternier reported. When evaluated by agent, the standardized incidence risk was significantly higher, at 22.3, for patients taking infliximab or adalimumab – both anti-TNF-alpha monoclonal antibody agents – compared with 3.0 for patients taking etanercept, which is a soluble TNF-alpha receptor therapy, she said at the meeting, sponsored by the American Society for Microbiology.
Similarly, in the case-control analysis, exposure to adalimumab or infliximab vs. etanercept was an independent risk factor for L. pneumophila infection, as was the first year of anti-TNF-alpha treatment, Dr. Lanternier said.
Compared with patients with L. pneumophila infection in the French population, anti-TNF-alpha–treated patients with the infection were younger and had a markedly lower infection-related mortality rate at 3.7% vs. the 10%-20% observed in the population not treated with anti-TNF-alpha drugs, said Dr. Lanternier, attributing the difference to the probability that the immunosuppressed patients are more closely monitored.
In a separate study also presented today, Dr. Alfred F. Sorbello, medical officer for the Food and Drug Administration reported an association between L. pneumophila infection-related mortality and onset of the infection within 90 days of initiating anti-TNF-alpha therapy in patients of younger mean age receiving concomitant steroids or methotrexate. This finding was based on a review of post-marketing adverse event reports for 21 of 80 patients from the FDA Adverse Event Reporting System between 1999 and 2010. Although the results are limited by the small number of patients included in the analysis because of missing data, lack of randomization, and underreporting, they do suggest a key role for TNF-alpha in host defense against L. pneumophila, and they point to the need for clinical vigilance with appropriate diagnostic testing and treatment in these patients, he stressed.
Dr. Lanternier disclosed no conflicts of interests. One of her co-investigators, Dr. Dominique Salmon, disclosed research relationships with Schering, Wyeth, and Abbott. Dr. Sorbello had no financial conflicts. The investigators did not give information on who funded the study.