title: Comparative safety of infliximab and etanercept on the risk of serious infections: does the association vary by patient characteristics?
abstract: OBJECTIVE
  Infliximab, a chimeric monoclonal anti-TNFα antibody, has been found to increase the risk of serious infections compared with the TNF receptor fusion protein etanercept in some studies. It is unclear whether the risk varies by patient characteristics. We conducted a study to address this question.
  
  
  METHODS
  We identified members of Kaiser Permanente Northern California who initiated infliximab (n = 793) or etanercept (n = 2692) in 1997-2007. Using a Cox model, we estimated the propensity-score-adjusted hazard ratio (HR) and 95% confidence interval (CI) of serious infections requiring hospitalization or opportunistic infections comparing infliximab initiators to etanercept initiators. We tested whether the adjusted HR differed by age, sex, race/ethnicity, body mass index, and smoking status.
  
  
  RESULTS
  The crude incidence rate of serious infections per 100 person-years was 5.4 (95%CI: 3.8, 7.5) in patients <65 years and 16.0 (95%CI: 10.4, 23.4) in patients ≥ 65 years during the first 3 months following treatment initiation. Compared with etanercept, the adjusted HR during this period was elevated for infliximab in patients <65 years (HR: 3.01; 95%CI: 1.49, 6.07), but not in those ≥ 65 years (HR 0.94; 95%CI: 0.41, 2.13). Findings did not suggest that the HR varied by the other patient characteristics examined.
  
  
  CONCLUSIONS
  An increased risk of serious infections associated with infliximab relative to etanercept did not appear to be modified by patients' sex, race/ethnicity, body mass index, or smoking status. There was an indication that the increased risk might be limited to patients <65 years. Additional studies are warranted to verify or refute this finding.
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA 02215, USA. darrentoh@post.harvard.edu
authors.forename: Sengwee
authors.initials: S
authors.lastname: Toh
authors.forename: Lingling
authors.initials: L
authors.lastname: Li
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Harrold
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bayliss
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.forename: Liyan
authors.initials: L
authors.lastname: Liu
authors.forename: Lang
authors.initials: L
authors.lastname: Chen
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Grijalva
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Herrinton
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy*; D002140:California / Q000453:epidemiology; D015331:Cohort Studies; D016208:Databases, Factual; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use; D007239:Infections / Q000453:epidemiology* / Q000209:etiology; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012306:Risk; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept