Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease.
BACKGROUND
Adverse events leading to discontinuation or dose reduction of thiopurine therapy occur in 9-28% of patients with inflammatory bowel disease.


OBJECTIVE
To evaluate the influence of thiopurine methyltransferase status and thiopurine metabolites in a large patient population for the risk of developing adverse event.


METHODS
Three hundred and sixty-four patients with inflammatory bowel disease and present or previous thiopurine therapy were identified from a local database.


RESULTS
The adverse event observed in 124 patients (34%) were more common in adults than children (40% vs. 15%; P < 0.001) and in low to intermediate (<or=9.0 U/mL red blood cell) than normal thiopurine methyltransferase activity (P = 0.02). Myelotoxicity developed later than other types of adverse event. An increased frequency of adverse event was observed in patients with tioguanine (thioguanine) nucleotide above 400 or methylated thioinosine monophosphate above 11 450 pmol/8 x 10(8) red blood cell. A shift to mercaptopurine was successful in 48% of azathioprine-intolerant patients and in all cases of azathioprine-induced myalgia or arthralgia.


CONCLUSIONS
A pre-treatment determination of thiopurine methyltransferase status might be appropriate as patients with low to intermediate thiopurine methyltransferase activity are more prone to develop an adverse event; determination of metabolite levels can be useful in the case of an adverse event. Mercaptopurine therapy should be considered in azathioprine-intolerant patients.
Hindorf
U
U
Department of Clinical Sciences, Division of Gastroenterology, Faculty of Medicine, Lund University, Lund, Sweden. ulf.hindorf@med.lu.se
Lindqvist
M
M
Hildebrand
H
H
Fagerberg
U
U
Almer
S
S
D000293:Adolescent; D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D013997:Time Factors
D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine