Optimising use of thiopurines in inflammatory bowel disease

Abstract

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are the most widely used immunosuppressive therapies in inflammatory bowel disease. Pretreatment measurement of thiopurine methyltransferase (TPMT) activity is recommended and although conventional practice is to use a dose of 2 mg/kg AZA (1 mg/kg 6-MP), higher doses of 2.5 mg/kg AZA or more may be required in some patients, particularly if TPMT activity is high. Dose raising is limited by toxicity, and a robust monitoring system is mandatory. Patients with side effects to AZA may tolerate 6-MP but pancreatitis is a contraindication to switching. Metabolite monitoring is not widely available but may be useful, particularly if non-compliance is possible or where metabolite shunting to 6-methylmercaptopurine is suspected, on the basis of non-response or toxicity. It may allow dose optimisation before switching to alternative immunosuppressants. The drug appears safe in pregnancy and breast feeding. Long term duration of therapy is a balance between benefits in relation to the underlying disease extent, activity and aggressiveness, and the risk of neoplasia, particularly lymphoma.

Ustekinumab for the Treatment of Crohn‘s Disease

“…However, pancreatitis, liver toxicity and neutropenia are important adverse events associated with this medication. Assessment of thiopurinemethyltransferase activity prior to initiation of therapy, frequent blood monitoring and careful dose titration are required to minimize toxicity [25]. Methotrexate has corticosteroid-sparing activity and is effective as a maintenance therapy [26,27], but is associated with teratogenicity, hepatotoxicity and pulmonary hypersensitivity reactions [28].…”

Vedolizumab for the treatment of inflammatory bowel diseases

“…Although multiple therapies for IBD currently exist, a substantial proportion of patients do not respond to conventional agents such as corticosteroids [2][3][4], antimetabolites [5][6][7][8] and tumor necrosis factor (TNF) antagonists [9][10][11][12][13][14]. Furthermore, important safety concerns exist regarding the use of these broad-spectrum [9,15,16] immunosuppressives [13,[17][18][19][20][21][22][23]. Specifically, the risks of serious infection and immunosuppressionrelated cancers such as lymphoma and nonmelanoma skin cancer, are relevant, especially in older patients.…”