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P573. A combination of low-dose thiopurine and allopurinol (ThioComp) is long-term efficacious and well-tolerated in IBD patients

S. Almer1, A. Wagner2, M. Måhl1, U. Hindorf3, 1Karolinska Institutet, Department of Medicine, Stockholm, Sweden, 2Blekinge Central Hospital, Department of Medicine, Karlskrona, Sweden, 3University Hospital, Gastoenterology and Hepatology, Lund, Sweden

Background

Up to half of thiopurine (TP)-treated patients with IBD experience adverse events or stop treatment due to lack of effect. An aberrant or ‘skewed’ metabolism is present in about 15 per cent of patients and is related to lack of response. A combination of low-dose thiopurine and allopurinol (ThioComp) reverses this kind of metabolism and leads to increased tolerance and effect.

Methods

Observational long-term follow-up study of patients treated with ThioComp. Results are given as median (range). Statistics used was the Wilcoxon's Signed Rank Test.

Results

58 patients (33 women; 38 (15–80) years) treated since January 2007 were included. Diagnoses were ulcerative colitis (n = 38), Crohn's disease (18), lymphocytic colitis (1), eosinophilic colitis (1). All patients had been treated with a thiopurine; azathioprine (AZA, n = 57), AZA and mercaptopurine (MP, n = 21), MP (1); 18 had previous or ongoing treatment with anti-TNF-antibodies. Half of the patients (n = 29) had suffered adverse events on previous TP-treatment. All had a normal TPMT genotype (*1/*1) and TPMT activity, 13.5 (10.1–23.7) U/ml pRBC. 52 (90%) displayed an aberrant metabolism with high meTIMP/TGN-ratios, 61 (22–541).

AZA was reduced to 29 (17–57)% and MP to 33 (17–40)% of previous TP-doses and 100 mg allopurinol daily was added two weeks later. TGN-levels increased from 147 (54–452) to 198 (44–512) after 2 weeks of ThioComp-treatment (P < 0.001) and to 255 (101–665) pmol/8×108 pRBC at 6 months (P < 0.001). meTIMP-levels decreased from 8650 (1000–74600) to 100 (0–7200) at 2 weeks (P < 0.001) and remained low, 100 (0–4200) pmol/8×108 pRBC, at 6 months (P < 0.001).

At last follow-up, 38 patients had continued treatment for 561 (53–2200) days; 34 (ITT 59%) were in clinical remission. The remaining 20 patients stopped treatment after 315 (14–1785) days due to lack of response (n = 9), wish to conceive (4; all in clinical remission), adverse events (4, of which 2 related to allopurinol), lack of compliance (1), or for unknown reason (2). Six of the 9 patients with lack of response underwent colectomy.

Conclusion

ThioComp treatment is very well tolerated and leads to dramatic changes in thiopurine metabolism resulting in long-standing clinical remission in two thirds of a group of difficult-to-treat IBD patients.