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P419. Low dose azathioprine and allopurinol in azathioprine intolerant patients: is it tolerated and is it effective in IBD?

H. Johnson, S. Weaver, S. McLaughlin, Royal Bournemouth Hospital, Gastroenterology, Bournemouth, United Kingdom

Background

Despite the advancement and introduction of new biological therapies, thiopurines remain effective treatment options for the maintenance of remission for both ulcerative colitis (UC) and Crohn's disease (CD). Once tolerated and therapeutic, thiopurines have many advantages over biologics for long-term maintenance therapy. However, it has been documented that intolerance and adverse events are common. We have previously published our 36 month follow-up data reporting that 56.5% of our patients stop thiopurines due to side effects, abnormal liver function tests (LFTs) or therapeutic failure.

Low dose azathioprine and allopurinol (LDAA) co-therapy is a well proven treatment option for patients who develop side effects or hepatotoxicity with standard dose azathioprine. LDAA has been used at our institution since 2010.

Aim: To report the safety, tolerability and therapeutic outcome at 12 months, for LDAA in patients who have failed standard dose azathioprine.

Methods

We maintain a prospective IBD data-base. After starting LDAA we monitor full blood count and LFTs weekly for 8 weeks. 6-Thioguanine (6-TGN) and 6-Methyl-mercaptopurine (6 MMPN) nucleotide levels are checked at 4–6 weeks. We searched our database for patients who started LDAA and had a minimum of 12 months follow-up. We recorded the indications for therapy, metabolite levels, and blood monitoring and clinical outcomes.

Results

62 patients were started on LDAA. 25 (40%) were male. Mean age was 47 (range 16–77). Disease type was UC, 21; CD, 35; IBD(U), 6. Reasons intolerant to standard dose azathioprine were: drug side effects (nausea and arthralgia) 24; hepatitis (ALT 2× upper limit normal) 20; Hypermethylation (TGN:MMPN ratio >11), 12. Gout 4; High TPMT 2.

At 12 months 44 (70%) remained on LDAA and were in clinical remission (HBI <1 for CD), (stool frequency <4 and no bleeding for UC) with therapeutic 6TGN levels on LDAA, of these 7 (11%) required additional treatment with biologic therapy.

Of the remaining 18 (29%) patients, 3 (5%) were lost to follow up and 1 (2%) chose to stop LDAA. 1 patient (UC) required a colectomy. 3 (5%) stopped LDAA to conceive. 10/62 (16%) remained intolerant and treatment was stopped.

One patient developed myelosuppression WCC <3 and stopped therapy. No patients developed abnormal LFTs on LDAA.

Conclusion

LDAA is well tolerated and effective in patients who failed standard dose azathioprine due to drug side effects and hepatotoxicity. This therapy results in resolution of hepatotoxicity and will allow more IBD patients to achieve clinical remission.