Randomised clinical trial: Individualised vs. weight-based dosing of azathioprine in Crohn's disease

T. Dassopoulos*, M. C. Dubinsky, J. L. Bentsen, C. F. Martin, J. A. Galanko, E. G. Seidman, R. S. Sandler, S. B. Hanauer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Background Azathioprine (AZA), a pro-drug metabolised to the active metabolites 6-tioguanine nucleotides (6TGN), is a steroid-sparing therapy for Crohn's disease (CD). Aim To investigate whether AZA therapy is optimised by individualised dosing based on thiopurine methyltransferase (TPMT) activity and 6TGN concentrations. Methods This multicentre, double-blind, randomised controlled trial compared the efficacy and safety of weight-based vs. individualised AZA dosing in inducing and maintaining remission in adults and children with steroid-treated CD. The primary outcome was clinical remission (CR) at 16 weeks. In the weight-based arm, subjects received 2.5 mg/kg/day. In the individualised dosing arm, the initial AZA dose was 1.0 mg/kg/day (if intermediate TPMT) or 2.5 mg/kg/day (if normal TPMT). Starting at week 5, the dose was adjusted to target 6TGN concentrations of 250-400 pmol/8 × 108 red blood cells (RBC), or to a maximal dose of 4 mg/kg/day. Results After randomising 50 subjects, the trial was stopped prematurely due to insufficient enrolment. In intention-to-treat analysis, CR rates at week 16 were 40% in the individualised arm vs. 16% in the weight-based arm (P = 0.11). In per-protocol (PP) analysis, week 16 CR rates were 60% in the individualised arm and 25% in the weight-based arm (P = 0.12). At week 16, median 6TGN concentrations in PP remitters and nonremitters were 216 and 149 pmol/8 × 108 RBC respectively (P = 0.07). Conclusions Despite trends favouring individualised over weight-based AZA dosing, there were no statistically significant differences in efficacy, likely due to low statistical power and inability to achieve the target 6TGN concentrations in the individualised arm. [Clinicaltrials.Gov Identifier Nct00113503].

Original languageEnglish (US)
Pages (from-to)163-175
Number of pages13
JournalAlimentary Pharmacology and Therapeutics
Issue number2
StatePublished - Jan 2014

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)


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