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* = Presenting author

P390 Thiopurines are more effective in Crohn's Disease than in Ulcerative Colitis, despite a global high rate of treatment failure: A single centre experience in the use of thiopurines in the era of biologics

C. Suarez Ferrer*, Y. Gonzalez Lama, G.P. Irene, V. Matallana Royo, M. Calvo Moya, M.I. Vera Mendoza, A.S.R. Leticia, L. Abreu Garcia

Hospital Puerta De Hierro, Gastroenterology, Madrid, Spain

Background

Thiopurines are widely used in inflammatory bowel disease(IBD) since they have shown efficacy in both ulcerative colitis(UC) and Crohn's disease(CD); whether or not thiopurines have different efficacy depending in the kind of IBD is still to be clarified. Treatment fails in a proportion of patients either due to adverse events or lack of efficacy. Biologics may have varied the clinical use of thiopurines as a primary treatment for IBD. We aimed to evaluate the current use of thiopurines in the era of biologics.

Methods

Retrospectively analyzed clinical records of all IBD patients treated with thiopurines at our centre, remain with an stable follow up. Dates of diagnosis and starting thiopurines were collected. We considered thiopurines failure(TF) if biologics had to be added to thiopurines or thiopurines had to be stopped due to lack of efficacy or adverse event(AE).

Results

575 patients included; 52,5% males, mean age 31yrs (range 17-84); 459CD, 116UC.

Overall, 304 patients (53%) experienced TF; a majority of them (67%) moved to or added biologics.

Median cumulative survival time of thiopurines (no TF) in CD was 86(95%IC 68-104) months and in UC was 23(95%IC 11-35) months (p<0.001). The cumulative proportion of CD patients that remained with no TF was 60%, 45%, 33% and 21%, and of UC patients was 35%, 25%, 12% and 8% at 50, 100, 150 and 200 months of treatment respectively (p<0.001). UC patients were twice as likely to experience thiopurines failure than CD patients (HR 2.2; 95%IC 1.7-2.8; p<0.001)

147 patients (25,5%) stopped thiopurines due to AE (8% digestive intolerance, 5% acute pancreatitis, 5% myelotoxicity, 4% hepatotoxicity). No differences between UC(31 %) and CD(24%) in probability of suffering AE forcing thiopurine withdrawal.

Most of those AE occurred in the early period of treatment: 67% of cases of digestive intolerance in the first year, 58% of cases of hepatotoxicity in the first 6 months and 80% of cases of acute pancreatitis in the first month. Myelotoxicity causing TF occurred along the follow up (mean 40 months, range 1-204).

157 patients had TF due to lack of efficacy. UC patients were twice as likely to experience thiopurines lack of efficacy than CD patients (HR 2.3; 95%IC 1.6-3.3; p<0.001)

Conclusion

In our experience, thiopurines were more effective in CD than in UC patients, although more than 50% of IBD patients experienced some kind of thiopurine treatment failure.

Current clinical usefulness of thiopurines as primary treatment for IBD seems to be modest in the long term favoring the use of biologics.