Relevance of thiopurine methyltransferase activity in inflammatory bowel disease patients maintained on low-dose azathioprine.
BACKGROUND
It is well-recognized that patients with low thiopurine methyltransferase activity are more susceptible to the development of bone marrow suppression side-effects.


OBJECTIVE
To study the impact of thiopurine methyltransferase activity on the clinical course of inflammatory bowel disease patients treated with low-dose azathioprine (< 2 mg/kg).


METHODS
We measured the thiopurine methyltransferase activity of blood samples from 113 inflammatory bowel disease patients who were taking azathiopurine, had discontinued azathioprine because of side-effects, or had never taken azathioprine. The thiopurine methyltransferase activity was compared with that of 17 healthy controls. Relapse rates and time to first relapse were compared in inflammatory bowel disease patients and stratified according to their thiopurine methyltransferase activity.


RESULTS
Patients who became neutropenic had a significantly lower mean thiopurine methyltransferase activity than that of patients who developed other side-effects (analysis of variance, P < 0.05). Survival curves were constructed (time to first relapse) for patients treated with low-dose azathioprine for thiopurine methyltransferase activities of < 20 and > 20 nmol/mL red blood cells/h. There was a significantly lower number of relapses in inflammatory bowel disease patients with lower thiopurine methyltransferase levels (P < 0.05).


CONCLUSIONS
The mean thiopurine methyltransferase activity was significantly lower in patients on a low dose of azathioprine in remission compared with those who relapsed. The thiopurine methyltransferase activity was significantly lower in patients who discontinued azathioprine due to neutropenia than in those who discontinued due to other side-effects.
Campbell
S
S
Department of Medical Sciences, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Kingstone
K
K
Ghosh
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D008780:Methyltransferases / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D012008:Recurrence; D016019:Survival Analysis
D015415:Biomarkers; D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine