title: The comparative risk of serious infections among rheumatoid arthritis patients starting or switching biological agents.
abstract: BACKGROUND
  It is unclear whether anti-tumour necrosis factor alpha and biological agents with different mechanisms of action have similar safety. This study evaluated the incidence of hospitalised infections among rheumatoid arthritis (RA) patients starting or switching various biological agents.
  
  
  METHODS
  Using a database from a large US healthcare organisation from January 2005 to August 2009, the authors identified enrollees with RA and their treatment episodes entailing the new use of a biological agent, stratified by no biological use in the previous year ('biological-free') or switching from a different biological agent ('switchers'). Outcomes were hospitalised infections identified using previously validated algorithms. Proportional hazards models estimated the hazard ratio of hospitalised infections, comparing each biological agent with infliximab.
  
  
  RESULTS
  Among 7847 biological treatment episodes, 63% were for biological-free patients and 37% for switchers. There were 364 hospitalised infections. Rates of hospitalised infection among biological-free patients and switchers were 4.6 and 7.0 per 100 person-years, respectively (p<0.0001). After multivariable adjustment controlling for biological-free/switcher status and other infection-related factors and compared with infliximab, users of abatacept (HR 0.68, 95% CI 0.48 to 0.96), adalimumab (HR 0.52, 0.39 to 0.71), etanercept (HR 0.64, 0.49 to 0.84) and rituximab (HR 0.81, 0.55 to 1.20) had lower rates of hospitalised infection. Patient risk factors contributed more to the risk of infection than did the risk associated with specific biological therapies.
  
  
  CONCLUSIONS
  The rate of hospitalised infections among RA patients was highest for infliximab. Most of the variability in patients' risk of infection was driven by factors other than biological agent exposure.
authors.affiliation: Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA. jcurtis@uab.edu
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.forename: Fenglong
authors.initials: F
authors.lastname: Xie
authors.forename: Lang
authors.initials: L
authors.lastname: Chen
authors.forename: John W
authors.initials: JW
authors.lastname: Baddley
authors.forename: Timothy
authors.initials: T
authors.lastname: Beukelman
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Saag
authors.forename: Claire
authors.initials: C
authors.lastname: Spettell
authors.forename: Raechele M
authors.initials: RM
authors.lastname: McMahan
authors.forename: Joaquim
authors.initials: J
authors.lastname: Fernandes
authors.forename: Kevin
authors.initials: K
authors.lastname: Winthrop
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Delzell
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D001424:Bacterial Infections / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology / Q000276:immunology; D001688:Biological Products / Q000009:adverse effects*; D016208:Databases, Factual; D057915:Drug Substitution / Q000706:statistics & numerical data; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D016867:Immunocompromised Host; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014481:United States / Q000453:epidemiology
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001688:Biological Products; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab