title: Dose tailoring of anti-tumour necrosis factor-alpha therapy delivers useful clinical efficacy in Crohn disease patients experiencing loss of response.
abstract: BACKGROUND
  'Dose tailoring' of anti-tumour necrosis factor alpha (TNF-α) therapy in Crohn disease (CD), by dose escalation, or shortening of dosing intervals, has been suggested to regain clinical response following a flare in a proportion of patients. However, reported outcome data are sparse and none exists from Australia.
  
  
  METHODS
  In an observational multicentre, retrospective study, the impact of anti-TNF-α dose tailoring on corticosteroid use, the need for surgery and physician perception of clinical efficacy was examined in a real-world setting at six Australian adult teaching hospitals. Demographics, disease characteristics, medications, indication for and duration of dose tailoring were documented.
  
  
  RESULTS
  Fifty-five CD patients were identified as requiring dose tailoring and secondary loss of response was the indication in 96%. Either adalimumab (64%) or infliximab (36%) was dose escalated for a median of 5 months (range 1-47), with a median of 20 months follow up (range 3-65). At 3 months, dose tailoring reduced the mean number of days on high-dose corticosteroids (45 vs 23, P = 0.01). Most (78%) patients remained resection free, and 73% of physicians reported good clinical efficacy of dose tailoring. Of those who de-escalated therapy due to induction of remission, long-term (>12 months) follow up and complete data on steroid use were available in 15/28, with 12/15 (80%) remaining steroid free at 1 year.
  
  
  CONCLUSIONS
  Short-term dose tailoring regains disease response in the majority of patients with CD. Of these, most will remain free of corticosteroids at 1 year after de-escalating therapy.
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Sydney, New South Wales, Australia; Centre for Inflammatory Bowel Disease, Fremantle Hospital, Fremantle, Western Australia, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Ghaly
authors.forename: S
authors.initials: S
authors.lastname: Costello
authors.forename: L
authors.initials: L
authors.lastname: Beswick
authors.forename: A
authors.initials: A
authors.lastname: Pudipeddi
authors.forename: A
authors.initials: A
authors.lastname: Agarwal
authors.forename: A
authors.initials: A
authors.lastname: Sechi
authors.forename: S
authors.initials: S
authors.lastname: Antoniades
authors.forename: B
authors.initials: B
authors.lastname: Headon
authors.forename: S
authors.initials: S
authors.lastname: Connor
authors.forename: I C
authors.initials: IC
authors.lastname: Lawrance
authors.forename: M
authors.initials: M
authors.lastname: Sparrow
authors.forename: A J
authors.initials: AJ
authors.lastname: Walsh
authors.forename: J M
authors.initials: JM
authors.lastname: Andrews
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D001315:Australia; D015331:Cohort Studies; D016001:Confidence Intervals; D003424:Crohn Disease / Q000175:diagnosis* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D016015:Logistic Models; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D012074:Remission Induction / Q000379:methods; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D062606:Tertiary Care Centers; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab
keywords: Crohn disease; adalimumab; anti-TNF-α; dose escalation; infliximab