title: Association between disease activity and risk of serious infections in subjects with rheumatoid arthritis treated with etanercept or disease-modifying anti-rheumatic drugs.
abstract: OBJECTIVE
  To determine the risk of serious infection in patients with rheumatoid arthritis (RA) receiving etanercept (ETN) or disease-modifying anti-rheumatic drugs (DMARDs) and to identify factors that predict a higher risk.
  
  
  METHODS
  Five-year data from the British Society of Rheumatology Biologics Register (BSRBR), a prospective observational study of patients with active RA treated with ETN, were used. These data were compared with a cohort of patients receiving DMARDs with active RA.
  
  
  RESULTS
  Total follow-up was 19,964 patient-years (py; ETN, 14,381 py; DMARDs, 5583 py). Over the study period, 651 first-recorded serious infections were reported (ETN, 469 [39.9 per 1000 py]; DMARDs, 182 [35.0 per 1000 py]). Overall the risk of serious infection was similar for the 2 treatments; however, in the first 6 months of treatment the hazard ratio (HR) was higher in the ETN than the DMARD group (1.979; p=0.015). A linear association was observed between the serious infection rate and disease-activity score in 28 joints (DAS28) in patients from each treatment group and overall (DAS28 <4, 27.1 per 1000 py; DAS28 ≥8, 64.4 per 1000 py; 7.5% increase in serious infection for each unit increase of DAS28 score at baseline). In a time-dependent analysis, a DAS28 change of 1 unit during follow-up predicted a 27% increase in serious infection rates.
  
  
  CONCLUSIONS
  No significant increase in the risk of serious infection was observed with ETN versus DMARDs over the 5-year study; a linear relationship existed between the serious infection rate and disease activity, as measured by DAS28.
authors.affiliation: Academic Unit of Musculoskeletal Disease, Leeds University, Leeds, UK. p.emery@leeds.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Gaia
authors.initials: G
authors.lastname: Gallo
authors.forename: Helen
authors.initials: H
authors.lastname: Boyd
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Morgan
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Currie
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Poole
authors.forename: Henk W
authors.initials: HW
authors.lastname: Nab
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D003141:Communicable Diseases / Q000139:chemically induced / Q000209:etiology* / Q000276:immunology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept