Evaluation of mucosal healing in Small Bowel Crohn’s disease treated with Certolizumab Pegol assessed by wireless capsule endoscopy

Abstract

Background: Certolizumab Pegol, a pegylated anti-TNF agent, is currently approved to reduce the signs and symptoms of Crohn's Disease (CD) and maintain clinical response in adult patients with moderately to severely active CD who have had inadequate response to conventional therapy. Biologic agents have demonstrated efficacy in the healing of gut mucosa leading to better long-term outcomes by sustaining steroid free remission, decreasing the need for major surgery and hospitalizations, and by improving patients overall quality of life. Prior studies have revealed certolizumab pegol induced endoscopically measured clinical response and remission at 10 and 54 weeks. Our primary objective was to evaluate mucosal healing assessed by wireless capsule endoscopy (WCE) using the Lewis scoring system (LS) in patients with moderate-to-severe small bowel Crohn's Disease (SBCD) treated with certolizumab pegol. Methods:We performed a prospective, single center, open-label trial in 15 patients with documented moderate-to-severe SBCD for a period of six months. All patients were randomized to receive standard induction therapy (400 mg) with certolizumab pegol at 0, 2, and 4 weeks, then standard maintenance dose therapy (400 mg) every 4 weeks through the end of the 28 week study period. Wireless capsule endoscopy with LS was performed at baseline, 12 weeks, and 24 weeks. Blood work, including complete metabolic panel (CMP), hemogram (HEMGPD), and C-reactive protein (CRP) were obtained as well as Crohn's Disease Activity Index (CDAI) and Short Inflammatory Bowel Disease Questionnaire (SIBDQ) at baseline and at every visit throughout the study period.Results: Eighteen patients underwent screening assessment with 15 patients qualifying to participate and 13 patients completing the trial. Of the 15 intent to treat patients, 6 were male and 9 were female with an average age of 33 (range 21-50) and a mean disease duration of 11.2 (range 1-26) years. Twelve patients had no prior CD surgery and 3 had previous small bowel resection. Ten of the 15 enrolling patients were secondary non-responders (SNR) to biologics; 4 lost response to both infliximab and adalimumab, 6 lost response to either infliximab or adalimumab, 3 were biologically naïve, and 2 had an allergic reaction to infliximab. None of the 10 biologically exposed patients were primary non-responders to other agents.Ten of the 13 patients (77%) who completed this trial demonstrated an overall improvement in mucosal healing, CDAI, and SIBDQ. Of those who responded to certolizumab pegol, the mean LS fell from 1663 at baseline to 226 at 24 weeks and the mean CDAI decreased from 256 at baseline to 140 at 28 weeks. The mean SIBDQ increased in responders from 40 at baseline to 51 by the end of study. Conclusions:This study demonstrates evidence of mucosal healing using certolizumab pegol in patients with moderate-to-severe SBCD. This study establishes a proof of concept that WCE used in conjunction with the LS is a valuable diagnostic test to assess mucosal healing in patients with SBC...

Small bowel capsule endoscopy and treat-to-target in Crohn's disease: A systematic review

“…All but one study had a prospective design. Most of these studies did not evaluate a specific treatment, except for two studies, one of which focused on adalimumab and azathioprine[42] and the other that focused on certolizumab pegol[43]. Another study was a sub-study of a prospective, randomized, double blind placebo-controlled study that assessed the safety, tolerability and efficacy of glatiramer acetate (Copaxone ® )[44].…”

Capsule Endoscopy in Suspected and Established Small Bowel Crohn’s Disease

“…Several recent studies evaluated the use of small bowel capsule endoscopy in the assessment of mucosal healing in patients diagnosed with Crohn's disease. Most of these studies did not evaluate a specific treatment, except for two studies, one of which focused on adalimumab and azathioprine [83] and the other that focused on certolizumab pegol [84]. In the other studies, there was no comparison between SBCE findings at baseline and during follow-up, because the most of patients in clinical remission had only one SBCE after treatment [85,86].…”