Dose tailoring of anti-tumour necrosis factor-alpha therapy delivers useful clinical efficacy in Crohn disease patients experiencing loss of response

Intern Med J. 2015 Feb;45(2):170-7. doi: 10.1111/imj.12621.

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.

Method: 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.

Conclusion: 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.

Keywords: Crohn disease; adalimumab; anti-TNF-α; dose escalation; infliximab.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adalimumab
  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage
  • Adult
  • Aged
  • Analysis of Variance
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Australia
  • Cohort Studies
  • Confidence Intervals
  • Crohn Disease / diagnosis*
  • Crohn Disease / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Infliximab
  • Logistic Models
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Remission Induction / methods
  • Retrospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Tertiary Care Centers
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab