1. P0866
Combination of Low dose Thiopurine and Allopurinol in patients with ulcerative colitis
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Marianne Kiszka-Kanowitz1, Klaus Theede1, Anette Mertz Nielsen1
1Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
Results
The active metabolite increased from mean 130 pmol/nmol Hgb (range ) to mean 243 pmol/nmol Hgb (range ) and MeMP decreased from 4158 pmol/nmol Hgb (range ) to mean 134 pmol/nmol Hgb (range: ) and ratio between MeMP and 6TGN decreased from 31 to 0, 55 upon changing from thiopurine mono-therapy to combination-therapy.
Five (14 %) patients were intolerant to combinations therapy and had to stop treatment. All patients had the same adverse event as in mono-therapy.
4 (11 %) patients had no or poor response to combination therapy, 2 had colectomy and 2 started treatment with anti-TNF, but continued treatment with Azathioprine and Allopurinol.
27 (75 %) patient responded to combination treatment and have since start of treatment been in steroid and anti-TNF free clinical remission. Thirteen for more then 2 years and the rest for more then 1 year.
Introduction
Thiopuine is used as a second line therapy in patient with ulcerative colitis (UC) failing 5-ASA treatment. However up to 50 % of patients treated with thiopurine fail this treatment due to intolerance or to lack of efficacy. A high ratio between Metylmercaptupurine (MeMP) and the active metabolite 6-Thioguanine-nucleotide (6-TGN) can be the explanation for intolerance and thiopurine-faliure in some patients.
Adding Allopurinol to a low dose of thiopurine changes the ratio between MeMP and 6-TGN, thereby decreasing the risk of some adverse events and at the same time increasing the efficacy fig. 1
Aim
To determent the tolerance and efficacy of combination of low dose of thiopurine and allopurinol in patient with UC.
Methods
A retrospective analysis of patient with CU starting combination therapy between 2010 and October 1th 2013 in a single IBD-center in Denmark.
36 UC patients were identified. 21 males and 15 females. Disease duration was mean 7 years (range 2 – 28 years). 2 patients had proctitis, 23 patients had left-sides colitis and 11 patients had pancolits.
The reason for starting combination therapy was: abnormal liver test in 8 patients, high MeMP/6-TGN ratio in 24 (15 was proven to fail mono-treatment with thiopurine), 3 other adverse events and 1 patient failing thiopurine treatment but without a high MeMP/6-TGN ratio.
When starting combination therapy 22 patients had active disease despite of treatment with systemic steroid in 3 patient, anti-TNF treatment in 5, steroid and TNF treatment in 3 patients. 15 patients had inactive disease but 3 patients were receiving steroid and 6 anti-TNF treatment.
Conclusions
Combination therapy with low dose thiopurine and allopurinol is well tolerated, cheap and a highly effective treatment in patients with CU and a high MeMP/6-TGN ratio experience intolerance to thiopurine mono-therapy or having poor or no response to thiopurine mono-therapy.
Steroid treatment
INF
Infliximab
ADA
Adalimumab
Active disease
Inactive disease
The graph illustrates treatment with steroid and anti-TNF.
This for a 24 month period prior to commencing combination therapy in the thirty patients that tolerated the treatment.
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