Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease

• Published in: Alimentary pharmacology & therapeutics Vol. 24; no. 2; pp. 331 - 342
• Main Authors: HINDORF, U., LINDQVIST, M., HILDEBRAND, H., FAGERBERG, U., ALMER, S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 15.07.2006; Blackwell
• Subjects: Adolescent; Adult; Azathioprine - administration & dosage; Azathioprine - adverse effects; Biological and medical sciences; Clinical Medicine; Digestive system; Female; Gastroenterologi; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - enzymology; Inflammatory Bowel Diseases - genetics; Klinisk medicin; Male; Medical and Health Sciences; Medical sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Methyltransferases - genetics; Methyltransferases - metabolism; Other diseases. Semiology; Pharmacology. Drug treatments; Retrospective Studies; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Time Factors; Human; Crohn disease; Modification; Treatment; Toxicity; Cohort study; Secondary effect; Digestive diseases; Intestinal disease; Public health; Inflammatory disease; Ulcerative colitis
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/j.1365-2036.2006.02977.x

Summary Background Adverse events leading to discontinuation or dose reduction of thiopurine therapy occur in 9–28% of patients with inflammatory bowel disease. Aims 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 (≤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 × 108 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.