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Original Research: Chest Infections |

Incidence and Risk Factors of Legionella pneumophila Pneumonia During Anti-Tumor Necrosis Factor TherapyLegionellosis and Anti-TNF Therapy: A Prospective French Study

Fanny Lanternier, MD; Florence Tubach, MD, PhD; Philppe Ravaud, MD, PhD; Dominique Salmon, MD, PhD; Pierre Dellamonica, MD, PhD; Stephane Bretagne, MD, PhD; Marie Couret, MD; Beatrice Bouvard, MD; Michel Debandt, MD; Isabelle Gueit, MD; Jean-Pierre Gendre, MD; Jean Leone, MD; Nathalie Nicolas, MD; Dider Che, PharmD, MPH; Xavier Mariette, MD, PhD; Olivier Lortholary, MD, PhD; for the Research Axed on Tolerance of Biotherapies Group*
Author and Funding Information

From the Université Paris Descartes (Drs Lanternier and Lortholary), Sorbonne Paris Cité, IHU Imagine, APHP, Hôpital Necker Enfants malades, Centre d’Infectiologie Necker Pasteur, Service de maladies infectieuses et tropicales, Paris; the Université Paris Diderot (Drs Tubach and Nicolas), Sorbonne Paris Cité, UFR de médecine, Paris; APHP (Dr Tubach), Hôpital Bichat, Département d’Epidémiologie et Recherche Clinique, Paris; INSERM (Dr Tubach), CIE 801, Paris; UMR-S 738 (Dr Ravaud), INSERM, Paris; UMR-S 738 (Dr Ravaud), Université Paris Diderot, Paris; the Université Paris Descartes (Dr Ravaud), Paris; the Centre d’Epidémiologie Clinique (Dr Ravaud), Hôpital Hôtel-Dieu, APHP, Paris; the Université Paris Descartes (Dr Salmon), Service de médecine interne, APHP, Hopital Cochin, Paris; the Service de maladies infectieuses et tropicales (Dr Dellamonica), CHU de Nice, Nice; the Service de parasitologie-mycologie (Dr Bretagne), groupe hospitalier Lariboisière-Saint-Louis, APHP, Paris; the Service de rhumatologie (Dr Couret), Hôpital de Valence, Valence; the Service de rhumatologie (Dr Bouvard), CHU, Angers; the Service de rhumatologie (Dr Debandt), Hôpital Robert Ballanger, Aulnay sous Bois; the Service d’infectiologie (Dr Gueit), Hôpital Charles Nicolle, Rouen; the Service de gastro-entérologie, Université Pierre et Marie Curie (Dr Gendre), Hôpital St Antoine, Paris; the Service de médecine Interne (Dr Leone), CHU de Reims, Reims; the Institut de Veille Sanitaire (Dr Che), Saint Maurice Cedex; APHP (Dr Mariette), hopital Bicêtre, Service de Rhumatologie, Le Kremlin Bicêtre; the Université Paris-Sud, Le Kremlin Bicêtre, (Dr Mariette); and INSERM U1012 (Dr Mariette), Le Kremlin Bicêtre, France.

Correspondence to: Olivier Lortholary, MD, PhD, Université Paris Descartes, Sorbonne Paris Cité, IHU Imagine, Hôpital Necker Enfants malades, APHP, Service des maladies infectieuses et tropicales, Centre d’Infectiologie Necker Pasteur, 149, rue de Sèvres, 75015 Paris, France; e-mail: olivier.lortholary@nck.aphp.fr


*

A list of RATIO participants is located in e-Appendixes 1 and 2.

This article was presented in part at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, September 12-15, 2010, Boston, MA, Abstract L1-1988.

Funding/Support: The RATIO was supported by a research grant from INSERM [A-02-02-PRO-AX-11-ed.3] (Réseau de recherche clinique 2003 and 2006) and by an unrestricted grant from Abbott Laboratories [convention ratio/hum/2007-2009], Schering-Plough (now Merck & Co, Inc), and Wyeth [convention 0711RC26, 0611RC19, 0911RC02, 0511RC03, 0411RC08, 0811RC02] (now Pfizer Inc).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(3):990-998. doi:10.1378/chest.12-2820
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Objective:  Our objective was to describe the incidence and risk factors of legionellosis associated with tumor necrosis factor (TNF)-α antagonist use.

Methods:  From February 1, 2004, to January 31, 2007, we prospectively collected all cases of legionellosis among French patients receiving TNF-α antagonists in the Research Axed on Tolerance of Biotherapies (RATIO) national registry. We conducted an incidence study with the French population as a reference and a case-control analysis with four control subjects receiving TNF-α antagonists per case of legionellosis.

Results:  Twenty-seven cases of legionellosis were reported. The overall annual incidence rate of legionellosis for patients receiving TNF-α antagonists, adjusted for age and sex, was 46.7 (95% CI, 0.0-125.7) per 100,000 patient-years. The overall standardized incidence ratio (SIR) was 13.1 (95% CI, 9.0-19.1; P < .0001) and was higher for patients receiving infliximab (SIR, 15.3 [95% CI, 8.5-27.6; P < .0001]) or adalimumab (SIR, 37.7 [95% CI, 21.9-64.9; P < .0001]) than etanercept (SIR, 3.0 [95% CI, 1.00-9.2; P = .06]). In the case-control analysis, exposure to adalimumab (OR, 8.7 [95% CI, 2.1-35.1]) or infliximab (OR, 9.2 [95% CI, 1.9-45.4]) vs etanercept was an independent risk factor for legionellosis.

Conclusions:  The incidence rate of legionellosis for patients receiving TNF-α antagonists is high, and the risk is higher for patients receiving anti-TNF-α monoclonal antibodies than soluble TNF-receptor therapy. In case of pneumonia occurring during TNF-α antagonist therapy, specific urine antigen detection should be performed and antibiotic therapy should cover legionellosis.

Trial registry:  ClinicalTrials.gov; No.: NCT00224562; URL: www.clinicaltrials.gov

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