Withdrawal of thiopurines in Crohn's disease treated with scheduled adalimumab maintenance: a prospective randomised clinical trial (DIAMOND2)

J Gastroenterol. 2019 Oct;54(10):860-870. doi: 10.1007/s00535-019-01582-w. Epub 2019 Apr 30.

Abstract

Background: The risk:benefit ratio of concomitant use of thiopurines with scheduled adalimumab (ADA) maintenance therapy for Crohn's disease is controversial. The aim of this study is to identify the influence of withdrawal of thiopurines in patients in remission with combination therapy in an open-label, randomised, controlled trial (DIAMOND2; UMIN000009596).

Methods: Patients in corticosteroid-free clinical remission (CFCR) for ≥ 6 months with ADA (40 mg, s.c., every other week) scheduled maintenance combined with thiopurines were randomised into two groups, "continue" (Con) or "discontinue" (Dis) group of thiopurines, whereas all other patients kept receiving scheduled ADA maintenance therapy for 52 weeks. The primary endpoint was the proportion of patients in CFCR at week 52. Secondary endpoints were endoscopic remission (ER), trough levels of ADA in serum, and safety.

Results: Fifty patients were randomised to Con or Dis groups. Characteristics of patients were not significantly different between the groups. CFCR and ER prevalence at week 52 were not significantly different between groups (log rank, P = 0.704, P = 1.000, respectively). Trough levels of ADA were not significantly different between groups (P = 0.515). The proportion of patients with AAA positivity at week 52 was not significantly different (P = 0.437). ER at week 0 was involved in ER and triple remission at week 52. No serious adverse effects were observed in either group.

Conclusion: Continuation of thiopurines > 6 months offers no clear benefit over scheduled ADA monotherapy. CFCR, ER, and ADA trough level at week 52 were not significantly different between groups. ER at week 0 may be involved in better long-term clinical outcomes.

Keywords: Adalimumab; Crohn’s disease; Thiopurines.

Publication types

  • Equivalence Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adalimumab / adverse effects
  • Adalimumab / therapeutic use*
  • Adolescent
  • Adult
  • Aged
  • Azathioprine / administration & dosage*
  • Azathioprine / adverse effects
  • Azathioprine / therapeutic use
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Crohn Disease / drug therapy*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Endoscopy, Gastrointestinal
  • Female
  • Gastrointestinal Agents / administration & dosage*
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / therapeutic use
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Prospective Studies
  • Remission Induction
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / adverse effects
  • Tumor Necrosis Factor Inhibitors / therapeutic use
  • Young Adult

Substances

  • Biomarkers
  • Gastrointestinal Agents
  • Immunosuppressive Agents
  • Tumor Necrosis Factor Inhibitors
  • C-Reactive Protein
  • Adalimumab
  • Azathioprine