Indicators of clinical response to treatment with six-mercaptopurine or azathioprine in patients with inflammatory bowel disease.

• Abstract: OBJECTIVES: There is some uncertainty regarding how to best dose and therapeutically monitor 6-mercaptopurine or azathioprine in patients with inflammatory bowel disease. The purpose of this study was to assess the relation between clinical response, 6-mercaptopurine metabolite levels, relative leukopenia, and drug dose. METHODS: 60 patients with inflammatory bowel disease who were on stable doses of 6-mercaptopurine or azathioprine for > or = 3 months and who had measurements of 6-mercaptopurine metabolite levels were evaluated. Patients were classified as complete responders (N = 24), partial responders (N = 7), or non-responders (N = 29). RESULTS: Drug dose was associated with clinical response when we analyzed adjusted doses based on molecular drug weight (P = 0.002). 6-Thioguanine levels also were associated with clinical response (P = 0.003) and the maximal difference between responders and non-responders was seen at 6-thioguanine levels greater than 260 pmol/8 x 10(8) RBC. Relative leukopenia, defined as white blood cell count less than either 5.0 or 4.0 K/uL, was not associated with clinical response (P = 0.13 and 0.77 respectively). CONCLUSIONS: 1. Drug dose and 6-thioguanine levels are related to clinical response in patients with inflammatory bowel disease on 6-mercaptopurine or azathioprine. 2. For 6-thioguanine levels, there is a fair amount of overlap, but maximal differentiation between responders and non-responders is seen at levels > 260 pmol/8 x 10(8) RBC. 3. Relative leukopenia does not correlate well with clinical response.
• Authors: Jean-Paul Achkar, Tyler Stevens, Kirk Easley, Aaron Brzezinski, Douglas Seidner, Bret Lashner (Affiliation: Center for Inflammatory Bowel Disease, Departments of Gastroenterology and Biostatistics, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. achkarj at ccf.org)
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 10 Issue 4 Pg. 339-45 (Jul 2004) ISSN: 1078-0998 [Print] United States
• PMID: 15475740 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antirheumatic Agents
• Immunosuppressive Agents
• Azathioprine
• 6-Mercaptopurine

Topics

• 6-Mercaptopurine (administration & dosage, pharmacology, therapeutic use)
• Adult
• Antirheumatic Agents
• Azathioprine (administration & dosage, pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Endpoint Determination
• Female
• Humans
• Immunosuppressive Agents (administration & dosage, pharmacology, therapeutic use)
• Inflammatory Bowel Diseases (drug therapy, pathology)
• Leukopenia (chemically induced)
• Male
• Middle Aged
• Treatment Outcome