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P029. Normalization of mucosal TNF-alpha as a criterion when to stop treatment with anti TNF in UC patients? A preliminary report

T. Olsen1, R. Rismo1, R. Goll1, G. Cui1, I. Christiansen1, J. Florholmen2

1Institute of Clinical Medicine, Tromsø, Norway; 2Department of Medical Gastroenterology, University Hospital North Norway, Tromsø, Norway

Background and Aims: There are no general guidelines if or when to stop treatment of the anti-TNF agent infliximab in ulcerative colitis. We have in earlier studies shown that the levels of TNF-alpha mRNA in colon mucosa correlate with the grade of inflammation in patients with ulcerative colitis and the clinical outcome of an induction therapy with infliximab is inversely associated with the pre-treatment levels of TNF-alpha. In this study we assessed whether measurement of TNF-alpha mRNA in mucosa could predict relapse of ulcerative colitis after induction therapy with infliximab (0, 2 and 6 weeks).

Methods: Sixty-five patients with moderate to severe ulcerative colitis were treated with Infliximab. Twenty-three (35%) patients achieved endoscopic remission after induction therapy. Colon mucosa biopsies were taken from 18 patients in clinical and endoscopic remission. TNF-alpha mRNA levels were measured by real-time PCR. The patients were followed, with regular clinical evaluations. Relapse was defined using endoscopic and clinical disease activity indices. The patients used 5-ASA and azathioprine as concomitant medication.

Results: Ten patients (62%) with UC had a relapse within the 12-month period. Mean TNF-alpha level in the relapse group (17710 copies/microgram mRNA) differed from those of the non-relapse group (8811 copies/microgram mRNA), but did not reach significant level (p-value = 0.1, Mann-Whitney test). At levels >10000 copies/microgram TNF-alpha mRNA (97% confidence limits of controls), 42% of the patients with low TNF-alpha relapsed within 12 months, compared with 77% of the patients with high TNF-alpha (p-value = 0.3, Mantel-Cox test, figure 1).

Conclusions: Normalization of mucosal TNF-alpha may be one of several criteria in the evaluation of when to stop treatment with infliximab.

Figure 1. Kaplan–Meier plot.