Adalimumab Maintenance Treatment in Ulcerative Colitis: Outcomes by Prior Anti-TNF Use and Efficacy of Dose Escalation

Dig Dis Sci. 2017 Feb;62(2):481-490. doi: 10.1007/s10620-016-4398-5. Epub 2016 Dec 19.

Abstract

Background: The impact of prior anti-TNF use on "real-life" outcomes of adalimumab therapy in ulcerative colitis (UC) is not well known.

Aim: To compare the influence of prior anti-TNF use on the outcomes of adalimumab maintenance treatment in UC patients. We also assessed the effectiveness of adalimumab dose escalation.

Methods: This retrospective multicenter cohort study included consecutive UC who advanced to an adalimumab maintenance regimen. Patients in whom adalimumab was discontinued prior to week eight of treatment were excluded. The co-primary efficacy endpoints were the cumulative probabilities of adalimumab failure-free survival and colectomy-free survival. We also assessed the need for and the effectiveness of adalimumab dose escalation.

Results: Of 184 UC on maintenance treatment with adalimumab, 116 (63%) had previous anti-TNF use. After a median follow-up of 23 months (interquartile range 13-49), 112 patients (60%) maintained corticosteroid-free clinical response. Sixty-nine patients (37%) had adalimumab failure, and 22 (12%) needed colectomy. Anti-TNF-naïve patients had significantly lower adjusted rates of adalimumab failure (hazard ratio [HR] 0.65; p < 0.001), adalimumab dose escalation (HR 0.35; p = 0.002), and need for colectomy (HR 0.26; p < 0.004). Seventy-six patients (41%) needed dose escalation after secondary loss of response, and 47% of these regained response after escalation. Short-term response after escalation was identified as a significant predictor of colectomy avoidance (HR 0.53; p = 0.007).

Conclusions: In this "real-life" cohort of UC patients on maintenance treatment with adalimumab, anti-TNF-naïve patients had significantly better long-term outcomes. Adalimumab dose escalation enabled recovery of response in nearly half of patients.

Keywords: Adalimumab; Colectomy; Dose escalation; Infliximab; Secondary loss of response; Ulcerative colitis.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adalimumab / therapeutic use*
  • Adult
  • Antirheumatic Agents / therapeutic use*
  • Cohort Studies
  • Colectomy / statistics & numerical data
  • Colitis, Ulcerative / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Substitution
  • Female
  • Humans
  • Infliximab / therapeutic use
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies
  • Treatment Failure
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab