title: Differences in biologic dose-escalation, non-biologic and steroid intensification among three anti-TNF agents: evidence from clinical practice.
abstract: OBJECTIVE
  To evaluate prevalence of dose escalation among RA patients in normal clinical practice treated with etanercept, adalimumab or infliximab and to estimate its economic impact.
  
  
  METHODS
  A retrospective observational study of 739 patients with RA receiving continuous treatment with etanercept (n=319), adalimumab (n=313) or infliximab (n=107) for 18 months. Dose escalation, intensification of concomitant DMARDs and risk of dose escalation were evaluated, as well as costs.
  
  
  RESULTS
  Significantly more patients prescribed adalimumab (10%, p<0.001) or infliximab (35%, p<0.001) experienced dose escalation compared with patients treated with etanercept (3%). DMARD or steroid dose adjustment, when added as criteria of escalation, occurred more often among patients treated with adalimumab (28%; p=0.022) or infliximab (47%; p<0.001) than those prescribed etanercept (19%). Independent of confounding covariates, hazard of dose escalation was significantly higher for either infliximab (28.1-fold) or adalimumab (4.9-fold) relative to etanercept. Escalation among subjects treated with either infliximab or adalimumab incurred statistically significant increases in total cost of care compared with non-escalators whereas such differences observed for subjects treated with etanercept were not significant.
  
  
  CONCLUSIONS
  Patients receiving monoclonal antibody therapies, adalimumab or infliximab, had significantly higher rates of dose escalation than patients receiving the soluble TNF receptor, etanercept, and related costs were higher.
authors.affiliation: University of Liverpool Academic Rheumatology Unit, University Hospital Aintree, Liverpool, UK. rjmoots@liv.ac.uk
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Moots
authors.forename: Boulos
authors.initials: B
authors.lastname: Haraoui
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
authors.forename: Jörn
authors.initials: J
authors.lastname: Kekow
authors.forename: Thierry
authors.initials: T
authors.lastname: Schaeverbeke
authors.forename: Alan
authors.initials: A
authors.lastname: Davis
authors.forename: Michael A
authors.initials: MA
authors.lastname: Tedeschi
authors.forename: Bruce
authors.initials: B
authors.lastname: Freundlich
authors.forename: David J
authors.initials: DJ
authors.lastname: Chang
authors.forename: Amitabh
authors.initials: A
authors.lastname: Singh
mesh_terms: D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D000068800:Etanercept; D005260:Female; D006304:Health Status; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept