title: Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry.
abstract: BACKGROUND
  Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs).
  
  
  OBJECTIVE
  To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors.
  
  
  METHODS
  A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case-control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease.
  
  
  RESULTS
  45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3 - 72.9); p<0.0001)or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use >10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002).
  
  
  CONCLUSIONS
  Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use >10 mg/day are independently associated with OI.
authors.affiliation: Service de Rhumatologie, Hôpital Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre.
authors.forename: D
authors.initials: D
authors.lastname: Salmon-Ceron
authors.forename: F
authors.initials: F
authors.lastname: Tubach
authors.forename: O
authors.initials: O
authors.lastname: Lortholary
authors.forename: O
authors.initials: O
authors.lastname: Chosidow
authors.forename: S
authors.initials: S
authors.lastname: Bretagne
authors.forename: N
authors.initials: N
authors.lastname: Nicolas
authors.forename: E
authors.initials: E
authors.lastname: Cuillerier
authors.forename: B
authors.initials: B
authors.lastname: Fautrel
authors.forename: C
authors.initials: C
authors.lastname: Michelet
authors.forename: J
authors.initials: J
authors.lastname: Morel
authors.forename: X
authors.initials: X
authors.lastname: Puéchal
authors.forename: D
authors.initials: D
authors.lastname: Wendling
authors.forename: M
authors.initials: M
authors.lastname: Lemann
authors.forename: P
authors.initials: P
authors.lastname: Ravaud
authors.forename: X
authors.initials: X
authors.lastname: Mariette
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects*; D004812:Epidemiologic Methods; D000068800:Etanercept; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects; D007155:Immunologic Factors / Q000009:adverse effects*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000139:chemically induced* / Q000453:epidemiology; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept