PTU-122A trial with mercaptopurine following azathioprine intolerance is a safe treatment strategy for the majority of patients with IBD

IntroductionAzathioprine intolerance (AZA-I) leads to withdrawal of therapy in up to 30% of patients with IBD. Smaller case series demonstrated that mercaptopurine (MP) could be a well tolerated alternative in selected patients.1 This study aims to further assess its tolerability, in a larger cohort of AZA-I patients, over a longer period of time, and to re-evaluate potential factors predictive of tolerance.MethodsA retrospective audit was made of 137 patients with IBD (78 women, median age at diagnosis 32years, 78 with CD, 59 with UC) who had been intolerant of AZA and then subsequently treated with MP.ResultsMP was tolerated by 58% of AZA-I patients (median follow-up 937days, median dose 0.91mg/kg). Tolerance was highest in patients with AZA related gastrointestinal intolerance (66%) and hepatotoxicity (61%), and lowest in patients with AZA related flu-like illness (40%). The number of patients with AZA induced neutropenia and pancreatitis were too small to draw firm conclusions (see Abstract PTU-122 table 1). Age at diagnosis was significantly associated with tolerability. Patients intolerant of MP were younger (28 vs 33 yro; p=0.024) and of those under the age of 40 only 55% tolerated MP compared with 69% of those aged 40years or over (p=Azathioprine-intolerant patients, subsequently treated with mercaptopurine (AZA-I/MP) grouped by azathioprine intoleranceAbstract PTU-122 Table 1Type of azathioprine intolerancenProportion with mercaptopurine tolerance (%)Type of mercaptopurine intoleranceProportion of patients where intolerance of mercaptopurine same as for azathioprine (%)80/137 (58%)GI IntoleranceFlu-like illnessHepatotoxicityNeutropeniaPancreatitisOther30/55 (55%)GI Intolerance*6744/67 (66%)142052014/23 (61%)Flu-like illness3514/35 (40%)410320210/21 (48%)Hepatotoxicity1811/18 (61%)1122012/7 (29%)Neutropenia43/4 (75%)0001001/1 (100%)Pancreatitis32/3 (67%)0000101/1 (100%)Other86/8 (75%)0000022/2 (100%)Unknown20/2 (0%)110000NA*Nausea, vomiting, abdominal pain, diarrhoea.Rash, Alopecia, Headaches, Itch, anaemia and acute kidney injury, acne.ConclusionConsistent with previous data, this, the largest series to date, with substantial follow- up, has shown that MP is a safe alternative for up to 60% of AZA-I patients, including some with a previous major intolerance. Patients with previous gastrointestinal intolerance or hepatotoxicity may be more likely to tolerate a trial of MP.Competing interestsNone declared.Reference1. Lees, et al. Aliment Pharmacol &