Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Angelberger, S; Schaeffeler, E; Teml, A; Petritsch, W; Shonova, O; Lukas, M; Bar-Meir, S; Dilger, K; Greinwald, R; Mueller, R; Stange, EF; Herrlinger, KR; Schwab, M; Reinisch, W.
Mucosal improvement in patients with moderate to severe postoperative endoscopic recurrence of Crohn's disease and azathioprine metabolite levels.
Inflamm Bowel Dis. 2013; 19(3):590-598
Doi: 10.1097/MIB.0b013e31827eea8b
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Petritsch Wolfgang
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- Abstract:
- 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. 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. 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 × 10(8) RBC; P = 0.017) or 6-MTGN (≥ 79.2 pmol/8 × 10(8) 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 × 10(8) 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. 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Aged -
- Azathioprine - metabolism Azathioprine - pharmacokinetics Azathioprine - therapeutic use
- Biomarkers - blood
- Crohn Disease - blood Crohn Disease - drug therapy Crohn Disease - pathology Crohn Disease - surgery
- Drug Administration Schedule -
- Drug Monitoring -
- Endoscopy, Gastrointestinal -
- Female -
- Guanine Nucleotides - blood
- Humans -
- Immunosuppressive Agents - metabolism Immunosuppressive Agents - pharmacokinetics Immunosuppressive Agents - therapeutic use
- Intestinal Mucosa - pathology
- Male -
- Middle Aged -
- ROC Curve -
- Recurrence -
- Severity of Illness Index -
- Thioguanine - analogs & derivatives Thioguanine - blood
- Thioinosine - analogs & derivatives Thioinosine - blood
- Thionucleotides - blood
- Treatment Outcome -
- Young Adult -
- Find related publications in this database (Keywords)
- azathioprine
- metabolite levels
- Crohn's disease
- postoperative recurrence
- mucosal healing