title: Incidence and risk factors of Legionella pneumophila pneumonia during anti-tumor necrosis factor therapy: a prospective French study.
abstract: 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 &lt; .0001) and was higher for patients receiving infliximab (SIR, 15.3 [95% CI, 8.5-27.6; P &lt; .0001]) or adalimumab (SIR, 37.7 [95% CI, 21.9-64.9; P &lt; .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.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT00224562; URL: www.clinicaltrials.gov.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, IHU Imagine, APHP, Hôpital Necker Enfants malades, Centre d'Infectiologie Necker Pasteur, Service de maladies infectieuses et tropicales, Paris.
authors.forename: Fanny
authors.initials: F
authors.lastname: Lanternier
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, UFR de médecine, Paris; APHP, Hôpital Bichat, Département d'Epidémiologie et Recherche Clinique, Paris; INSERM, CIE 801, Paris.
authors.forename: Florence
authors.initials: F
authors.lastname: Tubach
authors.affiliation: UMR-S 738, INSERM, Paris; UMR-S 738, Université Paris Diderot, Paris; Université Paris Descartes, Paris; Centre d'Epidémiologie Clinique, Hôpital Hôtel-Dieu, APHP, Paris.
authors.forename: Philppe
authors.initials: P
authors.lastname: Ravaud
authors.affiliation: Université Paris Descartes, Service de médecine interne, APHP, Hopital Cochin, Paris.
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.affiliation: Service de maladies infectieuses et tropicales, CHU de Nice, Nice.
authors.forename: Pierre
authors.initials: P
authors.lastname: Dellamonica
authors.affiliation: Service de parasitologie-mycologie, groupe hospitalier Lariboisière-Saint-Louis, APHP, Paris.
authors.forename: Stephane
authors.initials: S
authors.lastname: Bretagne
authors.affiliation: Service de rhumatologie, Hôpital de Valence, Valence.
authors.forename: Marie
authors.initials: M
authors.lastname: Couret
authors.affiliation: Service de rhumatologie, CHU, Angers.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bouvard
authors.affiliation: Service de rhumatologie, Hôpital Robert Ballanger, Aulnay sous Bois.
authors.forename: Michel
authors.initials: M
authors.lastname: Debandt
authors.affiliation: Service d'infectiologie, Hôpital Charles Nicolle, Rouen.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gueit
authors.affiliation: Service de gastro-entérologie, Université Pierre et Marie Curie, Hôpital St Antoine, Paris.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gendre
authors.affiliation: Service de médecine Interne, CHU de Reims, Reims.
authors.forename: Jean
authors.initials: J
authors.lastname: Leone
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, UFR de médecine, Paris.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nicolas
authors.affiliation: Institut de Veille Sanitaire, Saint Maurice Cedex.
authors.forename: Dider
authors.initials: D
authors.lastname: Che
authors.affiliation: APHP, hopital Bicêtre, Service de Rhumatologie, Le Kremlin Bicêtre; Université Paris-Sud, Le Kremlin Bicêtre, France; INSERM U1012, Le Kremlin Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, IHU Imagine, APHP, Hôpital Necker Enfants malades, Centre d'Infectiologie Necker Pasteur, Service de maladies infectieuses et tropicales, Paris. Electronic address: olivier.lortholary@nck.aphp.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
mesh_terms: D000068879:Adalimumab; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D000069285:Infliximab; D016952:Legionella pneumophila / Q000302:isolation & purification*; D007877:Legionnaires' Disease / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept