Prevention of Antidrug Antibody Formation to Infliximab in Crohn's Patients With Prior Failure of Thiopurines

Haggai Bar-Yoseph, Matti Waterman, Ronit Almog, Thomas Billiet, Séverine Vermeire, Bella Ungar, Henit Yanai, Iris Dotan, Shomron Ben-Horin, Yehuda Chowers

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims Combination thiopurine-infliximab (IFX) therapy is associated with reduced generation of antidrug antibodies (ADA) compared with IFX monotherapy. Whether past clinical response to thiopurine therapy bears an effect on ADA prevention is unknown. Methods This was a retrospective observational multicenter study of patients with Crohn's disease (CD) treated by IFX and thiopurines who had serial ADA measurements. Therapy was classified into past thiopurine response or its lack of, de novo combination, or IFX monotherapy. The primary endpoint was risk of ADA appearance. Results Out of 494 patients with serial ADA measurements 207 eligible patients were included in the final analysis. The 1-year cumulative risk of ADA development was similar in past thiopurine responders (19.3%) compared with past thiopurine failures (16.1%) (log rank P =.54). ADA was found in 46.6% of the monotherapy group and was significantly different compared with past thiopurine responders (P =.007) and past thiopurine failures (P =.007). The adjusted hazards for ADA development were significantly lower in past responders and past failures compared with the monotherapy group (hazard ratio, 0.47 [95% CI, 0.22–1.00] and 0.32 [95% CI, 0.11–0.93], respectively). Conclusions Thiopurines-IFX cotherapy in patients with Crohn's disease is associated with reduced ADA formation compared with IFX monotherapy. This is probably regardless of initial thiopurine therapeutic effect.

Original languageEnglish
Pages (from-to)69-75
Number of pages7
JournalClinical Gastroenterology and Hepatology
Volume15
Issue number1
DOIs
StatePublished - 1 Jan 2017

Bibliographical note

Publisher Copyright:
© 2017 AGA Institute

Keywords

  • Antidrug Antibodies
  • Crohn's Disease
  • Infliximab
  • Thiopurines

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

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