title: Non-viral opportunistic infections in new users of tumour necrosis factor inhibitor therapy: results of the SAfety Assessment of Biologic ThERapy (SABER) study.
abstract: OBJECTIVE
  To determine among patients with autoimmune diseases in the USA whether the risk of non-viral opportunistic infections (OI) was increased among new users of tumour necrosis factor α inhibitors (TNFI), when compared to users of non-biological agents used for active disease.
  
  
  METHODS
  We identified new users of TNFI among cohorts of rheumatoid arthritis (RA), inflammatory bowel disease and psoriasis-psoriatic arthritis-ankylosing spondylitis patients during 1998-2007 using combined data from Kaiser Permanente Northern California, two pharmaceutical assistance programmes for the elderly, Tennessee Medicaid and US Medicaid/Medicare programmes. We compared incidence of non-viral OI among new TNFI users and patients initiating non-biological disease-modifying antirheumatic drugs (DMARD) overall and within each disease cohort. Cox regression models were used to compare propensity-score and steroid- adjusted OI incidence between new TNFI and non-biological DMARD users.
  
  
  RESULTS
  Within a cohort of 33 324 new TNFI users we identified 80 non-viral OI, the most common of which was pneumocystosis (n=16). In the combined cohort, crude rates of non-viral OI among new users of TNFI compared to those initiating non-biological DMARD was 2.7 versus 1.7 per 1000-person-years (aHR 1.6, 95% CI 1.0 to 2.6). Baseline corticosteroid use was associated with non-viral OI (aHR 2.5, 95% CI 1.5 to 4.0). In the RA cohort, rates of non-viral OI among new users of infliximab were higher when compared to patients newly starting non-biological DMARD (aHR 2.6, 95% CI 1.2 to 5.6) or new etanercept users (aHR 2.9, 95% CI 1.5 to 5.4).
  
  
  CONCLUSIONS
  In the USA, the rate of non-viral OI was higher among new users of TNFI with autoimmune diseases compared to non-biological DMARD users.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA Medical Service, Birmingham VA Medical Center, Birmingham, Alabama, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Baddley
authors.affiliation: Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Winthrop
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Lang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
authors.forename: Liyan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Grijalva
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Delzell
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Beukelman
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Nivedita M
authors.initials: NM
authors.lastname: Patkar
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Fenglong
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Saag
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Herrinton
authors.affiliation: Department of Medicine, Boston, Brigham and Women's Hospital-Harvard University, Boston, Massachusetts, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perlman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology; D001688:Biological Products / Q000009:adverse effects* / Q000627:therapeutic use; D001691:Biological Therapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000139:chemically induced* / Q000453:epidemiology / Q000276:immunology; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States / Q000453:epidemiology
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha
keywords: DMARDs (biologic); Infections; Rheumatoid Arthritis; TNF-alpha; Tuberculosis