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P172. Mucosal TNF-alpha level as a criterion for when to stop treatment with adalimumab in patients with Crohn's disease? A preliminary report

R. Rismo1,2, T. Olsen1,2, R. Goll2,1, C. Guanglin1, I. Christiansen1, J. Florholmen1,2

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

Aim: Mucosal tumor necrosis factor-alpha (TNF-alpha) is a mediator of inflammation in Crohn's disease (CD). Adalimumab is a recombinant human monoclonal antibody against TNF-alpha, and is effective in CD for induction of remission. Our aim was to determine the tissue levels of TNF-alpha in CD patients treated with adalimumab to an apparent healed mucosa and the impact of this level on time to relapse after stop of treatment

Materials and Methods: CD patients with moderate to severe disease treated with adalimumab (80 mg/40 mg eow) for 10 weeks or longer, were included. Remission was defined as Crohn's disease activity index score <150 and endoscopic normalization of mucosa. Endoscopy was performed at week 12 or later in patients with clinical signs of remission, and adalimumab treatment was stopped when remission was achieved. Relapse was defined by endoscopic findings and/or increase in fecal calprotectin. Concomitant immunosuppressive therapy was performed in 32 of 39 patients. Measurements of gene expression of TNF-alpha by RT-PCR were performed in biopsies from patients in both remission and non-remission.

Results: A total of 21 (54%) out of 39 included patients achieved remission; 14 (67%) after standard induction treatment (10 wks), and 7 (33%) after prolonged treatment (16–32 wks). At 12 weeks or more of adalimumab treatment the mucosal TNF-alpha level was 15000 copies/ug (median) (range 3300–25000) in the remission group (n = 21), compared to 37000 copies/ug (median) (range 4500–135000) in the non-remission group (n = 18) (p < 0.005), and <9000 copies/ug (4000–8800 95% CI) in controls. TNF-alpha level was <12000 copies/ug in 10 (48%) of the 21 patients in remission. Of the 21 patients, 14 (67%) relapsed, whereas 6 patients are still in remission and 1 patient died in an accident. Median time to relapse after treatment was 32 weeks when TNF-alpha was <12000 copies/ug and 12 weeks when TNF-alpha was still elevated (p = 0.22) (fig 1).

Conclusion: Adalimumab induces remission to an apparent healed mucosa after 12 weeks or more, but the mucosal levels of TNF-alpha were not normalized in all patients. This may have an impact on time to relapse, and may be one of several criteria in the evaluation of when to stop treatment with adalimumab.

Figure 1. Kaplan–Meier plot.