Indicators of clinical response to treatment with six-mercaptopurine or azathioprine in patients with inflammatory bowel disease.
OBJECTIVE
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.
Center for Inflammatory Bowel Disease, Departments of Gastroenterology and Biostatistics, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. achkarj@ccf.org
Jean-Paul
JP
Achkar
Tyler
T
Stevens
Kirk
K
Easley
Aaron
A
Brzezinski
Douglas
D
Seidner
Bret
B
Lashner
D000328:Adult; D018501:Antirheumatic Agents; D001379:Azathioprine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000473:pathology; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine