Concerns and Side Effects of Azathioprine During Adalimumab Induction and Maintenance Therapy for Japanese Patients With Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]

J Crohns Colitis. 2019 Sep 19;13(9):1097-1104. doi: 10.1093/ecco-jcc/jjz030.

Abstract

Background: Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn's disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab.

Methods: In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group.

Results: There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher's exact test, p <0.001]. Kaplan-Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group.

Conclusions: Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

Keywords: Adalimumab; Crohn’s disease; anti-TNF-alpha antibody; thiopurine.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adalimumab / administration & dosage
  • Adalimumab / therapeutic use*
  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use*
  • Azathioprine / administration & dosage
  • Azathioprine / adverse effects*
  • Azathioprine / therapeutic use
  • Crohn Disease / drug therapy*
  • Drug Therapy, Combination / adverse effects
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Japan
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Patient Dropouts / statistics & numerical data
  • Prospective Studies
  • Risk Factors
  • Sex Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Immunosuppressive Agents
  • Adalimumab
  • Azathioprine