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Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e31827eea8b
Original Clinical Articles

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*

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Abstract

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 (Cav), 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 Cav 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 Cav 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.

© Crohn's & Colitis Foundation of America, Inc.

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