Institutional members access full text with Ovid®

Share this article on:

Mucosal Improvement in Patients With Moderate to Severe Postoperative Endoscopic Recurrence of Crohn’s Disease and Azathioprine Metabolite Levels

Angelberger, Sieglinde MD*; Schaeffeler, Elke PhD; Teml, Alexander MD*,†; Petritsch, Wolfgang MD; Shonova, Olga MD§; Lukas, Milan MD; Bar-Meir, Simon MD; Dilger, Karin MD**; Greinwald, Roland PhD**; Mueller, Ralph PhD**; Stange, Eduard F. MD††; Herrlinger, Klaus R. MD††,‡‡; Schwab, Matthias MD†,§§; Reinisch, Walter MD*

doi: 10.1097/MIB.0b013e31827eea8b
Original Clinical Articles

Background: The value of azathioprine metabolites (6-thioguanine nucleotides [6-TGN]) in monitoring clinical treatment response is still controversially discussed. Data regarding thiopurine metabolite levels and endoscopic improvement are lacking.

Methods: Data were analyzed post hoc from a 1-year, multicenter, double-blind, double-dummy, randomized trial comparing azathioprine 2.0 to 2.5 mg/kg per day versus mesalamine 4 g/d in a subset of 23 postoperative patients with Crohn’s disease (CD) treated with azathioprine and having moderate-to-severe endoscopic recurrence according to a modified 6-grade score. Red blood cell (RBC) concentrations of 6-TGN, 6-methyl-mercaptopurine ribonucleotides (6-MMPR), and 6-methyl-thioguanine nucleotides (6-MTGN) were indicated as follows: area under the concentration–time curve, average concentration (C av), and concentration at the final study visit.

Results: Overall, 74% of patients showed an improvement in the modified endoscopic score (P = 0.022). Median endoscopic score reduced from 4 at the baseline to 2 at the final visit. Patients with a high C av for 6-TGN (≥193 pmol/8 × 108 RBC; P = 0.017) or 6-MTGN (≥79.2 pmol/8 × 108 RBC; P = 0.035) significantly improved in endoscopic score, and the improvement in endoscopic score correlated with C av for 6-TGN (r = −0.51; P = 0.013). For concentration at the final visit, higher values for 6-TGN (≥142 pmol/8 × 108 RBC; P = 0.017) were associated with a better postoperative score. Sensitivity analysis revealed a significant correlation between 6-TGN (area under the concentration–time curve) and postoperative endoscopic improvement.

Conclusions: Our post hoc analysis from a double-blind, randomized trial suggests that higher RBC 6-TGN levels are associated with endoscopic improvement in patients with severe postoperative endoscopic recurrence of CD. Thus, our study provides first evidence on the utility of monitoring of thiopurine metabolites to achieve mucosal response in CD.

Article first published online 6 February 2013

*Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tübingen, Tübingen, Germany

Division of Gastroenterology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

§Gastroenterologicke oddeleni, Nemocnice Ceske Budejovice, Ceske Budejovice, Czech Republic

Klinické Centrum Iscare Lighthouse, Prague, Czech Republic

Chaim Sheba Medical Center, Tel Hashomer, Tel Hashomer, Israel

**Dr. Falk Pharma GmbH, Freiburg, Germany

††Department of Internal Medicine I, Robert-Bosch Krankenhaus, Stuttgart, Germany

‡‡Department of Internal Medicine I, Asklepios Klinik Nord – Heidberg, Hamburg, Germany

§§Department Clinical Pharmacology, University of Tübingen, Tübingen, Germany.

Reprints: Walter Reinisch, MD, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria (e-mail:

The study was funded by Dr. Falk Pharma GmbH, Freiburg, Germany. E. Schaeffeler and M. Schwab were supported by the Robert Bosch Foundation (Stuttgart, Germany), the Federal Ministry for Education and Research (BMBF, Berlin, Germany) grant 03 IS 2061C and the FP7-grant PITN-GA-2009-238132.

M. Schwab and W. Reinisch contributed equally.

Received June 01, 2012

Accepted June 18, 2012

© Crohn's & Colitis Foundation of America, Inc.
You currently do not have access to this article

To access this article:

Note: If your society membership provides full-access, you may need to login on your society website