P404 Calcineurin inhibitors are safe and effective for induction of remission in patients commencing vedolizumab for IBD
B. Christensen*, S.R. Goeppinger, R. Colman, D. Siddiqui, A. Yarur, A. Hirsch, A.A. Bochenek, A. Wichmann, A. Sakuraba, R. Cohen, D.T. Rubin
University of Chicago Inflammatory Bowel Disease Center, Gastroenterology, Chicago, IL, United States
Vedolizumab, a monoclonal antibody to alpha-4 beta-7 integrins recently approved for inflammatory bowel disease, has demonstrated efficacy in randomized clinical trials. However in these trials patients were not eligible to receive concomitant calcineurin inhibitors during induction. Therefore the success and safety of using calcineurin inhibitors as induction agents in combination with vedolizumab is unknown.
University of Chicago patients with CD and UC who received vedolizumab and who were followed for at least 12 weeks were fully characterized and included in an IRB-approved post-marketing study. Response and remission rates in those with concomitant exposure to tacrolimus or cyclosporine were specifically analyzed. Clinical activity was assessed using the Harvey Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI) at baseline and at pre-defined times of follow-up. Clinical response was defined as a reduction of 3 or more in HBI or SCCAI and clinical remission was defined as HBI less than or equal to 4 or SCCAI less than or equal to 2.
Between May 2014 and November 2014, 130 patients had initiated vedolizumab therapy. 69 patients (31 male, median age 35, CD 63.8%) had returned for post-induction follow-up at the time of this abstract. 7 of these patients (1 CD, 6 UC, 10.1%) received tacrolimus or cyclosporine during the induction phase of vedolizumab; 4 had active disease at baseline and 3 who were in clinical remission but calcineurin inhibitor-dependent. All 7 of these patients achieved or maintained clinical remission by week 14 of vedolizumab treatment and 5 (71.4%) were off all calcineurin inhibitors at this follow-up. Patients on concomitant calcineurin inhibitors v those on no calcineurin inhibitors achieved higher rates of clinical remission (100.0% v 34.2%) and response (80.0% v 51.2%). Apart from one episode of sinus congestion, no adverse events were reported with duel therapy with calcineurin inhibitors and vedolizumab.
Using a combination of cyclosporine or tacrolimus with vedolizumab to induce remission in inflammatory bowel disease is effective and safe. This induction strategy should be studied further in select patients.