Abstract

Background: To investigate the risk of relapse and the need of restarting biological treatment in patients affected of inflammatory bowel disease (IBD) in whom Anti-TNF drugs were discontinued after mucosal healing was proved, and the influencing factors on it. Methods: Retrospective study including 100 patients affected of IBD (70 Crohn's disease, 28 ulcerative colitis, 2 unclassified IBD) in whom biological treatment was stopped between June 2009 and May 2016, after mucosal healing had been proved. We have recorded the IBD characteristics, the biological treatment which reached mucosal healing, analytical and histopathological data, as well as the other IBD treatments used, and the needing of anti-TNF dose intensification at any time. We have analyzed the risk of relapse after discontinuation, the needing of restarting biological therapy, and the clinical response to it. Results: Anti-TNF (61 Infliximab, 37 Adalimumab) had been indicated after immunomodulators had failed in 65 cases. Steroid-dependence was the indication in 66 patients, and steroid-refractoriness in 32. 8 of them had needed dose intensification at any time. After anti-TNF withdrawal, 83 patients kept on receiving immunomodulator therapy. After discontinuation of anti-TNF drugs, 41 patients suffered disease relapse (average follow-up of 25 months); 34 of them needed to take up anti-TNF drugs again, and 28 of them achieved clinical response. Risk of retreatment on months 12, 24 and 36 was 21%, 42% and 48%, respectively. Univariate analysis showed lower risk of relapse in Crohn's disease with L2 extension (29% vs 54%, p 0.04) whereas it was higher when the indication was steroid-dependence (48% vs 25%, p 0.02), in the case of anti-TNF start up after immunomodulator had failed, and when there had been dose intensification needing (86% vs 36%, p 0.005). The same factors determined the future need of anti-TNF resuming, although the only factor achieving statistical significance was previous fail to immumomodulator drugs (49% vs 26%, p 0.02). In multivariate analysis, only previous fail to immumodulators, and intensification, predicted the relapse and the need of restarting anti-TNF drugs (not significant: p 0.07 and 0.05). Conclusions: At long term, about half of the patients need to restart biological therapy after discontinuation because of mucosal healing, with good response to it in more than 80% of the cases. In patients in whom immumodulator therapy fails prior to biological therapy, and in those who need anti-TNF dose intensification to reach mucosal healing, risk of relapse is higher. Nevertheless, the frequent good response to restarting biological therapy allows us to test discontinuation. Histological healing is not associated to better prognosis.

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