title: Frequency and effectiveness of dose increase of adalimumab, etanercept, and infliximab in daily clinical practice.
abstract: OBJECTIVE
  To describe the frequency and effectiveness of dose increase of adalimumab, etanercept, and infliximab in the treatment of rheumatoid arthritis (RA) in daily clinical practice.
  
  
  METHODS
  All RA patients with a dose increase of tumor necrosis factor (TNF)-blocking therapy between January 1997 and January 2008 were selected from a register including data from RA patients starting a first TNF-blocking agent (the Dutch Rheumatoid Arthritis Monitoring registry). The primary outcome was change in Disease Activity Score in 28 joints (DAS28) at 3 months after dose increase. Secondary outcomes were the change in DAS28 at 6 months after dose increase, the European League Against Rheumatism response rates, and the percentages of patients reaching a DAS28 of ≤3.2 at 3 and at 6 months after dose increase. Furthermore, the effectiveness of dose increase was assessed for the different reasons for dose increase: nonresponse, loss of response, and partial response.
  
  
  RESULTS
  During the study period, the dose was increased in 44 (12%) of the 368 adalimumab patients, 32 (8%) of the 420 etanercept patients, and 115 (36%) of the 323 infliximab patients. The change in DAS28 at 3 months and 6 months after dose increase was limited and only significant in etanercept patients at 3 months (-0.51; P = 0.035). Disease activity decreased significantly at 3 months from dose increase in the nonresponders and patients with loss of response (-0.66 and -0.99, respectively; both P = 0.001), but not in the partial responders.
  
  
  CONCLUSIONS
  Although dose increase was applied in all 3 TNF-blocking agents in daily clinical practice, these results suggest that the effectiveness of dose increase is limited.
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.blom@reuma.umcn.nl
authors.forename: M
authors.initials: M
authors.lastname: Blom
authors.forename: W
authors.initials: W
authors.lastname: Kievit
authors.forename: H H
authors.initials: HH
authors.lastname: Kuper
authors.forename: T L
authors.initials: TL
authors.lastname: Jansen
authors.forename: H
authors.initials: H
authors.lastname: Visser
authors.forename: A A
authors.initials: AA
authors.lastname: den Broeder
authors.forename: H L M
authors.initials: HL
authors.lastname: Brus
authors.forename: M A F J
authors.initials: MA
authors.lastname: van de Laar
authors.forename: P L C M
authors.initials: PL
authors.lastname: van Riel
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D012042:Registries; 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