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P114 Outcome of thiopurine-intolerant patients with Crohn's disease (CD)

J. Attali*, P. Seksik, A. Bourrier, I. Nion-Larmurier, L. Beaugerie, H. Sokol, J. Cosnes

APHP Saint-Antoine, Service de Gastroentérologie et nutrition, Paris, France

Background

Approximately 10% of CD patients treated with thiopurines (TP) have an early immuno-allergic intolerance that prevents continuation of treatment. The aim of this study was to assess if the impossibility to use TP jeopardizes the outcome of such patients, and to which extent, before and after the advent of anti-TNF.

Methods

From a total of 1805 consecutive CD patients who had in our center a first prescription of TP between 1994 and 2006, 114 patients (42M, 72F, 29 +/- 14 years) developed an early and definitive TP intolerance. Evolution of CD, collected prospectively, was compared in these patients and 228 controls matched 2/1 for age, sex, and disease duration, who received TP at a proximate date and tolerate this treatment. The patients were separated into 2 calendar cohorts: before (1994-2000, n=31) and after (2001-2006, n=83) the advent of anti-TNF. The primary end point was need for intestinal surgery. Secondary end points were percentage of patients-years out of clinical remission (because of flare or complication), use of anti-TNF, and occurrence of a perianal fistula or abscess.

Results

In case of intolerance, TP was replaced within the first year by methotrexate (n=60) or anti-TNF (n=18). Median follow-up was 130 months (IQR 105-158). The cumulative rate of intestinal surgery was 41% (CI 95% 30-54) at 10 years in TP-intolerant patients vs 29% (22-37) in controls (log rank p=0.01). The percentage of patient-years out of clinical remission was 41% (527/1294) in TP-intolerant patients vs. 32% (891/2813) in controls (p<0.0001). The 10-yr cumulative rates of anti-TNF use and development of a perianal perforating complication were 72% (61-81) and 20% (12-33), respectively, in TP-intolerant patients vs 48% (41-56) (p<0,001), and 17% (11-24) (p=0.12), respectively, in controls. In the first calendar cohort, differences between TP-intolerant patients and controls were significant (p<0.01) regarding cumulative rates of intestinal surgery (10-yr rates: 66% vs. 31%), anti-TNF use (67% vs 30%), and perforating anal complication (32% vs 18%), and percentage of patient-years out of clinical remission (43% vs 33%). In the cohort 2001-2006, compared to controls, TP-intolerant patients required more anti-TNF (10-yr rates: 73% vs 56%) and were more often out of remission (39% vs. 31%, p<0.01). However there was no difference regarding need for intestinal surgery (36% vs 28%) nor perianal perforating complication (15% vs 16%).

Conclusion

Compared to patients who tolerate TP, TP-intolerant patients undergo a more severe evolution of CD. The use of anti-TNF compensates only in part this disadvantage. These Results emphasize that TP still have an important room in the treatment of CD.