HomePublicationsCongress AbstractsAbstracts 2012Poster presentations: Clinical: Therapy and observation (2012)P341. A trial with mercaptopurine following azathioprine intolerance is a safe treatment strategy for the majority of patients with IBD

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Poster presentations: Clinical: Therapy and observation (2012)

P341. A trial with mercaptopurine following azathioprine intolerance is a safe treatment strategy for the majority of patients with IBD


E. Rhatigan1, I. Arnott2, C. Noble1, A. Shand1, J. Satsangui1, C. Lees1

1Western General Hospital, Molecular Medicine Centre, Gastrointestinal Unit, Edinburgh, United Kingdom; 2Western General Hospital, GI Unit, Edinburgh, United Kingdom



Background: Azathioprine 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.

Methods: A retrospective audit was made of 137 patients with IBD (78 women, median age at diagnosis 32 years, 78 with CD, 59 with UC) who had been intolerant of AZA and then subsequently treated with MP.

Table 1. AZA‑I patients and outcome of MP treatment. (Other: rash, alopecia, itch, headaches, anaemia)
Azathioprine intoleranceNumberMercaptopurine intoleranceSame intolerance
  Mercaptopurine toleranceGastrointestinal intoleranceFlu-like illnessHepatotoxicityNeutropeniaPancreatitisOther 
Gastrointestinal intolerance6744 (66%)142 52 14/23 (61%)
Flu-like illness3514 (40%)41032 210/21 (48%)
Hepatotoxicity1811 (61%)1122 12/7 (29%)
Neutropenia43 (75%)   1  1/1 (100%)
Pancreatitis32 (67%)    1 1/1 (100%)
Other86 (75%)     22/2 (100%)
Unknown20 (0%)11    N/A

Results: MP was tolerated by 58% of AZA‑I patients (median follow-up 937 days, median dose 0.91 mg/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 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 40 years or over (p ≤ 0.001). Type of disease was statistically associated with tolerance and patients with CD were more likely to be intolerant of MP (38/57 (67%) vs 19/57 (33%); p = 0.032). A significant trend to a shorter time period between AZA and MP in the tolerant group (median 10 (IQR: 1–71) vs 34 days (IQR: 5–390); p = 0.014) was observed. Tolerance was unaffected by TPMT (30.8 vs 33.0 pmol/hb/ml, p = 0.16), site of disease, behaviour, family history, smoking, surgery or, extra-intestinal manifestations.

Conclusions: Consistent 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.

1. C.W. Lees, A.K. Maan, B. Hansoti, J. Satsangi & I.D. R. Arnott (2007), Tolerability and safety of mercaptopurine in azathioprine-intolerant patients with inflammatory bowel disease, Blackwell Publishing Ltd, Alimentary Pharmacology & Therapeutics, 220–227, 27.