Positive pharmacokinetic effect of azathioprine co-medication on infliximab trough levels is dose-dependent

Dig Liver Dis. 2019 Aug;51(8):1112-1116. doi: 10.1016/j.dld.2019.05.001. Epub 2019 May 28.

Abstract

Background: Thiopurines seem to have positive effect on the pharmacokinetics of anti-tumor necrosis factor biologics. It has been suggested that a reduced dose of thiopurines is sufficient to achieve this synergism.

Aims: To assess the differences of infliximab (IFX) trough levels according to the dose of concomitantly used azathioprine (AZA).

Patients & methods: All IBD patients treated with IFX (Remicade®) in two IBD centres between November 2015 and April 2017 were eligible. Infliximab trough levels were assessed by ELISA (Ridascreen®, R-Biopharm). The differences in IFX trough levels according to AZA dose were analyzed statistically.

Results: In total, 125 patients were included, 42 pts (33.6%) on infliximab monotherapy, 83 pts (66.4%) using combined immune suppression. The respective median IFX levels according to AZA dose were as follows: group 1 (no concomitant AZA) 2.83 μg/ml (range 0-12); group 2 (AZA dose less than 1 mg/kg) 4.91 μg/ml (range 0.09-15.36); group 3 (AZA dose 1 < 2 mg/kg) 5.67 (range 0.16-16.97); group 4 (AZA dose above 2 mg/kg) 7.53 μg/ml (range 1.15-8.73). The differences in IFX trough levels between the respective groups according to AZA dose were statistically significant (p = 0.0159).

Conclusion: The positive effect of azathioprine on infliximab levels seems to be dependent on the dose of concomitantly used azathioprine.

Keywords: Azathioprine; Inflammatory bowel disease; Infliximab; Pharmacokinetics.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies / blood*
  • Azathioprine / administration & dosage*
  • Azathioprine / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Gastrointestinal Agents / administration & dosage*
  • Gastrointestinal Agents / pharmacokinetics
  • Humans
  • Inflammatory Bowel Diseases / blood
  • Inflammatory Bowel Diseases / drug therapy*
  • Infliximab / administration & dosage*
  • Infliximab / pharmacokinetics
  • Male
  • Middle Aged
  • Remission Induction
  • Slovakia
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Young Adult

Substances

  • Antibodies
  • Gastrointestinal Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Azathioprine