title: Dose escalation of the anti-TNF-alpha agents in patients with rheumatoid arthritis. A systematic review.
abstract: OBJECTIVE
  To estimate the proportion of rheumatoid arthritis (RA) patients on anti-tumour necrosis factor (anti-TNF) who require dose escalation.
  
  
  METHODS
  Systematic review of the scientific literature. Infliximab, etanercept and adalimumab studies in RA were considered. Primary outcome was the proportion of patients requiring dose escalation. American College Rheumatology (ACR) and Disease activity score (DAS) responses post-escalation were assessed when available.
  
  
  RESULTS
  From 1801 references, 16 studies with 8510 patients were included. Of all the infliximab patients, 53.7% underwent dose escalation. Fourty-four per cent of the infliximab patients experienced dose increase and 8.3%, frequency increase. The ACR20 response to dose escalation ranged from 27 to 36% and DAS28 improved from 5.2 to 4.5 in one study and from 4.1 to 3.7 in another. Of the etanercept patients, 17.5% experienced a dose increase but changes on the mean dose were not statistically significant.
  
  
  CONCLUSIONS
  Dose escalation is common in patients treated with infliximab, and less frequent with etanercept. In a proportion of patients, the dose escalation seems effective. The design and evidence level of the available studies limit the strength of the conclusions.
authors.affiliation: Rheumatology Service, Hospital Universitário Virgen Macarena, Seville, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Ariza-Ariza
authors.forename: F
authors.initials: F
authors.lastname: Navarro-Sarabia
authors.forename: B
authors.initials: B
authors.lastname: Hernández-Cruz
authors.forename: L
authors.initials: L
authors.lastname: Rodríguez-Arboleya
authors.forename: V
authors.initials: V
authors.lastname: Navarro-Compán
authors.forename: J
authors.initials: J
authors.lastname: Toyos
mesh_terms: D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004334:Drug Administration Schedule; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D007155:Immunologic Factors / Q000008:administration & dosage*; D000069285:Infliximab; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept