Serious thiopurine adverse effects and discontinuation among inflammatory bowel disease patients in Sri Lanka

Abstract

INTRODUCTION & OBJECTIVES: Thiopurines such as azathioprine and 6-mercaptopurine use for long term is not uncommon for patients with inflammatory bowel disease (IBD). Severe thiopurine adverse effects are dependent on thiopurine methyltransferase (TPMT) activity. TPMT testing prior to commencing thiopurine has been suggested to identify individuals with low TPMT activity, so that thiopurine use can be avoided in such patients. There is very limited data on thiopurine adverse effects among IBD patients in South Asia. METHODS: Patients with histologically proven IBD [ulcerative colitis (UC), Crohn’s disease (CD)], diagnosed over a ten year period from May 2005 to April 2015, with at least one year of regular follow up, were included from Colombo North Teaching Hospital and National Hospital of Sri Lanka (two main IBD referral centers). Frequency of thiopurine use, thiopurine adverse effects (myelosuppression and hepatotoxicity), and drug discontinuation were noted. RESULTS: A total of 214 patients were eligible for inclusion [UC-148 (69.2%), 75 (50.7%) males, median follow up (IQR) 55.0 (30-81) months; CD-66 (30.8%), 31 (47.0%) males, median follow up (IQR) 41.5 (26.5-68) months]. Thiopurine was used in 74 (50.0%) and 60 (90.9%) of UC and CD patients, respectively. Very few had severe thiopurine adverse effects that led to discontinuation of treatment [UC-4 (2.7%); CD-4 (6%)]. These were myelosuppression (6 patients) and hepatotoxicity (2 patients). CONCLUSION: In this cohort of Sri Lankan IBD patients, severe thiopurine adverse effects resulting in discontinuation of treatment was uncommon. Routine TPMT testing prior to thiopurine use does not seem warranted in the Sri Lankan setting.