title: Treatment benefit or survival of the fittest: what drives the time-dependent decrease in serious infection rates under TNF inhibition and what does this imply for the individual patient?
abstract: OBJECTIVE
  To examine the risk of serious infection conveyed by tumour necrosis factor α (TNFα) inhibitors in the treatment of rheumatoid arthritis (RA).
  
  
  METHODS
  Data from patients with RA enrolled in the German biologics register RABBIT were used for analysis. Baseline patient characteristics, time-varying risk factors (treatment changes, functional capacity) and selection processes caused by dropout, death or switching to non-anti-TNF treatment were taken into account to estimate the adjusted incidence rate ratios (IRR(adj)) of serious infection during treatment with TNF inhibitors compared with non-biological disease-modifying antirheumatic drug treatment.
  
  
  RESULTS
  Data were available on 5044 patients, in whom 392 serious infections occurred. The crude rates of serious infections in patients treated with TNF inhibitors declined over the first 3 years of observation (from 4.8 to 2.2/100 patient-years). This decline was driven by (1) treatment termination or loss to follow-up in patients at increased risk and (2) a risk reduction through decreasing glucocorticoid doses and improvement in function. Adjusted for selection processes and time-varying risk factors, the following parameters assessed at baseline (age, chronic diseases) or at follow-up prior to the infection were significantly associated with an increased risk: age >60 years, chronic lung or renal disease, low functional capacity, history of serious infections, treatment with glucocorticoids (7.5-14 mg/day, IRR(adj) 2.1 (95% CI 1.4 to 3.2); ≥ 15 mg/day, IRR(adj) 4.7 (95% CI 2.4 to 9.4)) and treatment with TNFα inhibitors (IRR(adj) 1.8 (95% CI 1.2 to 2.7)).
  
  
  CONCLUSIONS
  Reasons for the decline in infection rates observed at the group level were identified. The results enable expected infection rates to be calculated in individual patients based on their risk profiles.
authors.affiliation: Correspondence to Dr A Strangfeld, Programmbereich Epidemiologie, Deutsches Rheuma-Forschungszentrum Berlin, ein Leibniz Institut, Charitéplatz 1, 10117 Berlin, Germany. strangfeld@drfz.de
authors.forename: A
authors.initials: A
authors.lastname: Strangfeld
authors.forename: M
authors.initials: M
authors.lastname: Eveslage
authors.forename: M
authors.initials: M
authors.lastname: Schneider
authors.forename: H J
authors.initials: HJ
authors.lastname: Bergerhausen
authors.forename: T
authors.initials: T
authors.lastname: Klopsch
authors.forename: A
authors.initials: A
authors.lastname: Zink
authors.forename: J
authors.initials: J
authors.lastname: Listing
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology; D001688:Biological Products / Q000009:adverse effects* / Q000627:therapeutic use; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005260:Female; D005858:Germany / Q000453:epidemiology; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000453:epidemiology; D008171:Lung Diseases / Q000150:complications / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000139:chemically induced* / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha