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P350 Mucosal and histologic response to cyclosporin in ulcerative colitis: a cohort study

C. Fron1, G. Belleannée2, E. Chabrun3, F. Poullenot1, C. Subtil1, F. Zerbib3, M. Capdepont1, D. Laharie*1

1CHU de Bordeaux, Gastroenterologie, Pessac, France, 2CHU de Bordeaux, Pathologie, Pessac, France, 3CHU de Bordeaux, Gastroenterologie, Bordeaux, France

Background

Cyclosporine (CsA) has demonstrated its efficacy for treating patients with steroid-refractory acute severe ulcerative colitis (UC). However, little is known about the impact of this drug on endoscopic and histologic responses, which are considered as relevant therapeutic goals in UC. The aim of the present study was to assess mucosal healing (MH) and histological remission (HR) rates under CsA and their predictive value on UC course.

Methods

All consecutive patients admitted in two academic hospitals from January 2008 to January 2014 for steroid-refractory acute severe UC and treated with intravenous CsA were eligible. CsA was given as a bridge therapy to azathioprine in all patients. Only primary clinical responders to CsA who had endoscopic assessments at entry and at the end of the treatment were analyzed. They were followed until relapse or until July 2014 for non-relapsing patients. MH was defined by a Mayo endoscopic subscore 0 or 1. HR was defined by absence of basal plasmocytosis or by a Geboes score < 3.1 (Bitton et al, Am J gastroenterol 2001, Bessisow et al, Am J Gastroenterol 2012). The primary outcome was UC relapse, defined by occurrence of clinical symptoms associated with inflammatory endoscopic lesions leading to systemic therapeutic change (steroids, immunosuppressant or biologic agent) or colectomy.

Results

Among 39 patients who received CsA, 18 were excluded (14 for CsA primary non-response and 4 for absence of endoscopic assessment). Therefore, 21 (54%) patients (11 W; median age: 36 [range: 16-69] years) were analyzed. Median duration of CsA treatment was 103 [60 - 145] days. MH was achieved in 81% patients, HR in 85% according to basal plasmocytosis and in 65% according to Geboes score. With a median follow-up duration of 42 [0.3 - 66.1] months after CsA withdrawal, survival rates without UC relapse at 1 and 2 years were respectively 79% and 79% in patients with MH as compared to 50% and 25% to those without MH (p=0.040). They were similar in patients achieving HR and in those without HR whatever the definition used. On multivariate analysis, Mayo endoscopic subscore 0 was the sole prognosis factor associated with absence of relapse with a relative risk of 12 (95%CI: 1.05-136.79).

Conclusion

CsA provided 81% of MH in patients with severe refractory UC responding to this drug and 65-85% of HR. With a long follow-up duration, complete MH was associated with absence of UC relapse. As observed with other UC treatments, these data with CsA further confirm the high prognostic value of MH.