P532 Efficacy of combination therapy with cyclosporin and vedolizumab in inflammatory bowel diseases refractory to anti-TNF agents

Abstract

Vedolizumab it is a promising agent in IBD patients refractory to anti-TNF therapy. However, a potential slower response has been documented in both GEMINI 2 and 3 trials, and also in clinical settings. Because of the slower onset of action of vedolizumab, monotherapy does not seem to be effective in more severe cases of IBD. However, cyclosporin is an effective “rescue therapy” which may serve as a rapidly acting “bridge” to maintenance therapy with the slowly acting agents such as thiopurines in patients with severe UC. The aim of the study to report our experiences with the use of combined cyclosporine and vedolizumab therapy in active IBD failed to respond to anti TNF therapy. Vedolizumab was registered in Hungary in 2016. Data were collected retrospectively from the Hungarian Registry on Vedolizumab therapy. We assessed clinical and endoscopic disease activity with CDAI and Mayo Score. Clinical outcome and safety profile was registrated. Six of 106 vedolizumab-treated patients (four colonic CD, two UC) diagnosed with moderate-to-severe IBD requiring rescue therapy received intravenous cyclosporine of 4 mg/kg for 5 days following oral treatment a mean of 69 days before the initiation of vedolizumab. The reason for late initiation of vedolizumab therapy was the awaiting time of the evaluation process. Cyclosporine levels were closely monitored and adjusted if needed. Mean values of CD activity index and partial Mayo score were 276 and 8, respectively. Three patients received concomitant immunomodulator therapy and 3 had azathioprine intolerance. Primary and secondary non-response to previous anti-TNF therapy was reported in two and four patients, while two patients developed infusion reaction. Combination therapy was effective in all cases and cyclosporine was discontinued after a mean of 130 days. After the induction phase of vedolizumab, control colonoscopy was performed. One patient had complete mucosal healing, the other patients had moderate regression in mucosal inflammation. Side-effect of cyclosporine occurred in one patient leading to the discontinuation of the drug after the third infusion of vedolizumab. After the induction phase of vedolizumab, one patient underwent colectomy because of severe CD. On the basis of our data we do think that cyclosporin therapy is a useful and safe option in combination with vedolizumab induction therapy in moderate-to-severe activity of IBD.