title: Adalimumab dose escalation and dose de-escalation success rate and predictors in a large national cohort of Crohn's patients.
abstract: OBJECTIVE
  Adalimumab is efficacious in inducing and maintaining remission in Crohn's disease but dose escalation is needed in 30-40% after 1 year. Attempts for dose de-escalation have not been studied. This study aimed to assess the need for, predictors, and outcome of dose escalation and de-escalation in a large cohort of adalimumab treated Crohn's patients.
  
  
  METHODS
  All consecutive patients treated with open label adalimumab for active Crohn's disease from the participating centres were included in this cohort study. A detailed retrospective chart review was performed to look for possible factors predicting outcome.
  
  
  RESULTS
  Eighty four percent of 720 patients had a primary response and were followed up for a median of 14 months. Thirty four percent needed escalation after a median of 7 months (0-55 months). Multivariate predictors for dose escalation were the following: prior anti-TNF use (p<0.0001), no concomitant azathioprine or <3 m (p<0.02) and abnormal CRP at start (p<0.05). Dose escalation re-induced response for at least 6 months in 67%. Only abnormal CRP at start correlated with failure of dose escalation (p=0.02). Dose de-escalation was attempted in 54% and was successful in 63%. After a median follow-up of 14 m adalimumab was discontinued in 29% of patients.
  
  
  CONCLUSIONS
  In this study real life nationwide cohort of Crohn's patients treated with adalimumab dose escalation was needed in 34% and was successful in 67%. Dose de-escalation was attempted in 54% and was successful in 63%. Overall 71% of patients maintained long term response on adalimumab.
authors.affiliation: Department of Internal Medicine, H.-Hart ziekenhuis Roeselare-Menen, Belgium. fbaert@hhr.be
authors.forename: Filip
authors.initials: F
authors.lastname: Baert
authors.forename: Elien
authors.initials: E
authors.lastname: Glorieus
authors.forename: Cathérine
authors.initials: C
authors.lastname: Reenaers
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.forename: Harald
authors.initials: H
authors.lastname: Peeters
authors.forename: Dennis
authors.initials: D
authors.lastname: Franchimont
authors.forename: Olivier
authors.initials: O
authors.lastname: Dewit
authors.forename: Philippe
authors.initials: P
authors.lastname: Caenepeel
authors.forename: Edouard
authors.initials: E
authors.lastname: Louis
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D001379:Azathioprine / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069285:Infliximab; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D002097:C-Reactive Protein; D000069285:Infliximab; D000068879:Adalimumab; D001379:Azathioprine