Prior anti-TNF Exposure Research Articles

Long-term remission with certolizumab pegol in Crohnʼs disease: Efficacy over 5 years in patients with no prior anti-TNF agent exposure (precise 3 study)

Long-term remission with certolizumab pegol in Crohnʼs disease: Efficacy over 5 years in patients with no prior anti-TNF agent exposure (precise 3 study)

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

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.

Long-Term Remission With Certolizumab Pegol in Crohn's Disease: Efficacy Over 5 Years in Patients With No Prior Anti-TNF Agent Exposure (PRECiSE 3 Study)

Purpose To assess remission rates in patients who received certolizumab pegol for 6 months (26 weeks) in PRECiSE 2, and for a further 4.5 years in PRECiSE 3, and to determine if remission rates are affected in patients without previous tumor necrosis factor (TNF) inhibitor exposure. Methods Patients completing PRECiSE 2 (NCT00152425) were eligible to enter PRECiSE 3 (NCT00160524) and receive certolizumab pegol 400 mg every 4 weeks. Efficacy and safety data for patients who received certolizumab pegol in PRECiSE 2 and continued with open-label certolizumab pegol treatment in PRECiSE 3 are presented. The HarveyBradshaw Index (HBI) was used to measure disease activity (remission = score of ≤4). Remission rates were analyzed from the baseline of PRECiSE 2 in the PRECiSE 3 ITT population and in a subset of this population who had never received infliximab (IFXnaive). Remission rates were calculated using observed case analyses and nonresponder imputation (NRI). Results Of the 141 patients in the PRECiSE 3 population, 114 were IFXnaive. At the start of PRECiSE 3 (Week 0), 75% (105/141) and 78% (89/114) of the total and IFX-naive populations were in remission, respectively. Remission rates for the total PRECiSE 3 population after 1, 2, 3, 4, and 5 years (observed case) were 75%, 84%, 82%, 79%, and 91%, respectively, and 76%, 83%, 82%, 81%, and 89%, respectively, for the IFXnaive patients (Table). Remission rates for the total PRECiSE 3 population after 1, 2, 3, 4, and 5 years (NRI) were 65%, 49%, 35%, 23%, and 21%, respectively, and 65%, 47%, 37%, 25%, and 21%, respectively, for the IFX-naive patients. No new safety signals were observed and there were no unexpected serious adverse events. Conclusions Among patients who initially responded to certolizumab pegol induction therapy and remained in PRECiSE 3, continuous certolizumab pegol 400 mg therapy provided long-term remission for 5 years, including a subset of PRECiSE 3 patients receiving certolizumab pegol with no previous exposure to infliximab.