P524 Systematic review of calcineurin inhibitors (CNI) and vedolizumab (VDZ) combination therapy in acute severe ulcerative colitis (ASUC)

Abstract

Introduction: Patients with acute severe ulcerative colitis (ASUC) may be refractory to treatment with steroids and anti-tumour necrosis factor agents (anti-TNF). Ciclosporin inhibitors (CNI) have been used effectively as a fast-acting bridge to slower-onset immunomodulators in thiopurinenaive patients; however concerns over toxicity limit prolonged use of CNI as maintenance therapy. Patients who are azathioprine-exposed or anti- TNF-refractory have limited medical treatment options, often resulting in colectomy. Combination of CNI as induction therapy, together with slower-acting but potentially safer vedolizumab (VDZ) has recently been used in patients with severe inflammatory bowel disease (IBD). We aim to review the utility of this combination treatment in ASUC. Aims &Methods: A systematic bibliographic review was conducted on PubMed using the keywords ?vedolizumab?, ?calcineurin inhibitors?, ?inflammatory bowel disease?, and ?severe ulcerative colitis?. Additional studies were identified by manual search of reference lists. 6 articles were identified within the period 2013 to March 2019. Only English language publications and abstracts on use of combination CNI+VDZ in adult ASUC patients were included. 1 paediatric study (1), 1 case report(6) and 1 abstract (2) (ASUC data not reported) were excluded. Results: There were 2 prospective observational studies(3,4) [N= 30] and 1 retrospective study (5) [N=39]. Patients were refractory to conventional treatment with steroids [1 study, N=17] and/or anti-TNF therapy [N=48]. CNI (ciclosporin or tacrolimus) was used for induction of remission in majority of cases, or as rescue agent in those failing induction with Vedolizumab [subgroup of 1 study, N=7]. In 2 studies, IV cyclosporine 2 mg/kg titrated to goal trough level 300- 400 or Tacrolimus 0.05mg-0.1mg/kg/d with target levels 10-14ng/mL was started; a week later, CNI-responsive patients were given vedolizumab (IV 300mg at week 0,2,6 then maintenance 8-weekly) and CNIs were stopped after 8-12 weeks per protocol. In another study, VDZ was initiated on average 30days after CNI, with average combination CNI+VDZ of 64 days. Combination CNI+VDZ showed good short-term efficacy (1 study: 14/15 in remission). At 1 year, there was a respectable colectomy-free rate of 75% (2 studies, N=39/52), comparable to other studies with infliximab/ciclosporin combined with azathioprine. In those receiving steroids at baseline, Steroid-free remission was achieved in 18/36 = 50% at week 14. Serious adverse events (N=7) were attributed to CNIs; there were no deaths. Conclusion: Preliminary studies of combination CNI and VDZ in patients with ASUC appear promising. However, the methodology in these limited studies was heterogenous. Further prospective trials are needed for the confirmation of the utility and efficacy of this treatment strategy in the management of ASUC.