Open Label Investigation of Mucosal Healing in Patients with Small Bowel Crohnʼs Disease Treated with Certolizumab Pegol Assessed by Wireless Capsule Endoscopy

Abstract

Purpose: The efficacy of certolizumab pegol (CZP), a pegylated anti-TNF agent for the induction and maintenance of response and remission in adult patients with active Crohn's disease has been demonstrated in randomized controlled trials. Prior study has shown improvement of mucosal healing associated with improved long term outcomes and lower need for major surgery. The MUSIC trial demonstrated CZP-induced endoscopic response and remission in Crohn's disease at 10 weeks and 54 weeks. Our primary objective is to assess CZP and endoscopic healing using Lewis scoring system (LS) with wireless capsule endoscopy (WCE) in patients with moderate-to-severe Crohn's disease. Methods: We performed a prospective open label trial in 5 patients with documented moderate-to-severe Crohn's disease for a period of six months. All patients were given standard induction dose therapy with CZP at 0, 2, 4 weeks, then every 4 weeks until 6 months. WCE was performed at baseline, 16 weeks and 26 weeks. Blood work including CMP, HEMGPD and CRP were obtained, as well as Crohn's disease activity index (CDAI) and Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Results: Five patients were enrolled in this trial with an average age of 36.2 years; there were 2 males, 3 females, with an average disease duration of 16.6 years. Of the 5 patients, 4 had no prior surgery and one had prior small bowel resection. Four out of five patients were secondary non-responders (SNR) to biologics; 2 having lost response to both infliximab and adalimumab, one each to infliximab and adalimumab alone and one biologically naïve patient. The mean LS at baseline was 1,976 with CDAI of 289 and SIBDQ of 34. At 26 weeks, the LS fell to a mean of 639, with significant mucosal healing in 4 out of 5 patients, with only one patient showing non-healing at the end of the study period. All patients achieved significant reduction in CDAI of greater than 100 points, with a mean CDAI of 133 at 26 weeks and improvement in the SIBDQ to 56.8 at the end of study. Conclusion: This study demonstrates significant mucosal healing in 4 of 5 patients treated with open label CZP as assessed by serial WCE studies in moderate-to-severe CD, despite prior anti-TNF exposure. The study establishes proof of concept that WCE and the use of the LS is a valuable diagnostic test to assess mucosal healing in patients with small bowel Crohn's disease treated with CZP. CZP is well tolerated in this population with no safety issues. Continued study utilizing WCE and treatment with CZP is warranted. Disclosure: Dr. Shafran - Research Support: UCB. This research was supported by an industry grant from UCB.