title: Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry.
abstract: OBJECTIVE
  The risk of severe infection is a crucial factor in the assessment of the short-term risk:benefit ratio of biologic drugs in rheumatoid arthritis (RA). There is no increase in severe infections in RA patients treated with rituximab (RTX) in controlled trials, but this has not yet been assessed in daily practice. We undertook this study to investigate the occurrence of and risk factors for severe infections in off-trial patients using data from the AutoImmunity and Rituximab (AIR) registry.
  
  
  METHODS
  The AIR registry was set up by the French Society of Rheumatology. The charts of patients with severe infections were reviewed.
  
  
  RESULTS
  Of the enrolled patients, 1,303 had at least 1 followup visit at 3 months or later, with a mean ± SD followup period of 1.2 ± 0.8 years (1,629 patient-years). Eighty-two severe infections occurred in 78 patients (5.0 severe infections per 100 patient-years), half of them in the 3 months following the last RTX infusion. Multivariate analysis showed that chronic lung disease and/or cardiac insufficiency (odds ratio 3.0 [95% confidence interval 1.3-7.3], P = 0.01), extraarticular involvement (odds ratio 2.9 [95% confidence interval 1.3-6.7], P = 0.009), and low IgG level (<6 gm/liter) before initiation of RTX treatment (odds ratio 4.9 [95% confidence interval 1.6-15.2], P = 0.005) were significantly associated with increased risk of a severe infection.
  
  
  CONCLUSIONS
  The rate of severe infections in current practice is similar to that reported in clinical trials. The risk factors for severe infections include chronic lung and/or cardiac disease, extraarticular involvement, and low IgG before RTX treatment. This suggests that serum IgG should be checked and the risk:benefit ratio of RTX discussed for patients found to have low levels of IgG.
authors.affiliation: Hôpitaux Universitaires de Strasbourg and Université de Strasbourg, Strasbourg, France. jacques-eric.gottenberg@chru-strasbourg.fr
authors.forename: J-E
authors.initials: JE
authors.lastname: Gottenberg
authors.forename: P
authors.initials: P
authors.lastname: Ravaud
authors.forename: T
authors.initials: T
authors.lastname: Bardin
authors.forename: P
authors.initials: P
authors.lastname: Cacoub
authors.forename: A
authors.initials: A
authors.lastname: Cantagrel
authors.forename: B
authors.initials: B
authors.lastname: Combe
authors.forename: M
authors.initials: M
authors.lastname: Dougados
authors.forename: R M
authors.initials: RM
authors.lastname: Flipo
authors.forename: B
authors.initials: B
authors.lastname: Godeau
authors.forename: L
authors.initials: L
authors.lastname: Guillevin
authors.forename: X
authors.initials: X
authors.lastname: Le Loët
authors.forename: E
authors.initials: E
authors.lastname: Hachulla
authors.forename: T
authors.initials: T
authors.lastname: Schaeverbeke
authors.forename: J
authors.initials: J
authors.lastname: Sibilia
authors.forename: G
authors.initials: G
authors.lastname: Baron
authors.forename: X
authors.initials: X
authors.lastname: Mariette
mesh_terms: D000361:Agammaglobulinemia / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D001424:Bacterial Infections / Q000150:complications / Q000276:immunology*; D000075202:Contraindications; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D000069283:Rituximab; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab