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

Clin Gastroenterol Hepatol. 2017 Jan;15(1):69-75. doi: 10.1016/j.cgh.2016.06.028. Epub 2016 Jul 9.


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.

Keywords: Antidrug Antibodies; Crohn's Disease; Infliximab; Thiopurines.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Antibody Formation*
  • Crohn Disease / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / immunology*
  • Infliximab / administration & dosage
  • Infliximab / immunology*
  • Male
  • Mercaptopurine / administration & dosage
  • Mercaptopurine / analogs & derivatives*
  • Mercaptopurine / immunology
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult


  • Immunologic Factors
  • azathiopurine
  • Infliximab
  • Mercaptopurine