Endoscopic improvement of mucosal lesions in patients with moderate to severe ileocolonic Crohn's disease following treatment with certolizumab pegol

Abstract

Objective: To evaluate the efficacy of certolizumab pegol (CZP) in improving endoscopic lesions in patients with active ileocolonic Crohn's disease (CD).

Methods: This phase IIIB multicentre open-label clinical trial enrolled 89 adult patients with active endoscopic disease (ulceration in ≥2 intestinal segments with a Crohn's Disease Endoscopic Index of Severity (CDEIS) score ≥8 points). Patients received subcutaneous CZP 400 mg at weeks 0, 2 and 4 and every 4 weeks up to week 52. Endoscopic evaluations were performed at weeks 0, 10 and 54. The primary outcome was mean change in CDEIS score at week 10; secondary outcome measures included endoscopic response (decrease in CDEIS score >5 points), remission (CDEIS score <6), complete remission (CDEIS score <3) and mucosal healing (no ulcer) at weeks 10 and 54.

Results: In the intention-to-treat population (n=89) the mean±SD CDEIS score was 14.5±5.3 at baseline; the mean decrease in CDEIS score at week 10 was 5.7 (95% CI 4.6 to 6.8, p<0.0001). Rates of endoscopic response, endoscopic remission, complete endoscopic remission and mucosal healing at week 10 were 54%, 37%, 10% and 4%, respectively. At week 54 the corresponding rates were 49%, 27%, 14% and 8%, respectively. The safety profile was consistent with that of previous CZP trials.

Conclusions: Following CZP treatment in patients with active CD, endoscopic lesions were improved as shown by the decrease in mean CDEIS score and by endoscopic response and remission rates. These benefits were achieved as early as week 10 and were generally maintained through week 54.

Clinical trial registration number: NCT00297648.

Conflict of interest statement

Competing interests: XH received funding from UCB Pharma, Baxter, Fresenius Kabi, Vifor for advisory activity, as a member on an advisory board and from Abbott, Nestlé, Norgine, Nutricia and Schering-Plough for educational activities. ML served as a consultant for UCB Pharma and participated in continuing medical education events supported by unrestricted educational grants from UCB Pharma. He died on 26 August 2010. YB has been reimbursed by Schering-Plough and Abbott for attending several conferences and has been paid by Schering-Plough, Abbott, Ferring, Norgine, HAC Pharma, BMS and Teva for running educational programmes. OD has received fees from MSD, Abbott and Ferring for speaking and from MSD and Abbott for educational activities. J-LD has no disclosure information or competing interests to report. MM has received payment for conducting clinical studies for Roche Pharma, MSD Pharma, Ferring, Merckle-Recordati, Shire, Merz Pharma, Viofor Pharma, Abbott, UCB Pharma, Dr. Falk Pharma and AstraZeneca and has been reimbursed for attending conferences by several of these companies. GD'H has received consulting fees from UCB Pharma and has been paid to serve on Speakers Bureau/Advisory Committees for UCB Pharma. KM was an employee of UCB Pharma during development of this manuscript. EE is an employee of UCB Pharma. SV has received fees from UCB, Abbott, Centocor and MSD for running educational programmes and has a research chair from UCB. HB-B has been reimbursed by Abbott, Schering-Plough and UCB for attending several conferences and has received fees from Abbott and Schering-Plough for speaking. TM received lecture fees, grant support and research support from UCB Pharma. PM has served as a consultant for UCB Pharma and has participated in continuing medical education events supported by unrestricted educational grants from UCB Pharma. J-YM has no competing interests to report. J-FC has received consulting fees from Abbott Laboratories, ActoGeniX, Albireo Pharma, Amgen, AstraZeneca, Bayer AG, Biogen Idec, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Cellerix, Centocor, ChemoCentryx, Cosmo Technologies, Danone Research, Elan Pharmaceuticals, Genentech, Giuliani SpA, Given Imaging, Glaxo Smith Kline, Hutchison MediPharma, MSD, Millennium Pharmaceuticals (now Takeda), Neovacs, Ocera Therapeutics, Pfizer, Shire Pharmaceuticals, Prometheus Laboratories, Sanofi-Aventis, Schering-Plough, Synta Pharmaceuticals, Teva, Therakos, UCB Pharma and Wyeth; has served on advisory committees for Abbott Laboratories, Centocor, Danone, Elan, MSD, Millennium Pharmaceuticals (now Takeda), Schering-Plough and UCB Pharma; has received speaking fees from Abbott Laboratories, Centocor, Elan Pharmaceuticals, Given Imaging, MSD, Otsuka America Pharmaceutical, Schering-Plough, Shire Pharmaceuticals, Tillotts Pharma and UCB Pharma; has received grant support from Abbott Laboratories, Astra-Zeneca, Ferring, MSD, Schering-Plough and UCB Pharma; and has stock ownership for Intestinal Biotech Development, Lille, France.

Figures

Figure 1

Study design. Loss of response was defined as both a Crohn's Disease Activity Index (CDAI) score >150 points and a minimum increase in CDAI of 70 points at two consecutive visits by week 10. CZP, certolizumab pegol; q2w, every 2 weeks; q4w, every 4 weeks; CDEIS, Crohn's Disease Endoscopic Index of Severity.

Figure 2

Patient dispositions. *Includes one case each of anal fistula, colonic stenosis, colon cancer, enterocutaneous fistula, gingivitis and pregnancy on oral contraceptive. AE, adverse event; CDEIS, Crohn's Disease Endoscopic Index of Severity.

Figure 3

Ulceration classification in patients with endoscopic evaluation at baseline/week 10 and baseline/week 54.

Figure 4

Agreement between local and central Crohn's Disease Endoscopic Index of Severity scores at week 0 (baseline) by the Bland–Altman method. The difference between local and central scores (positive values indicate a higher local score) as a function of their average value. The solid line represents the mean difference and the dashed lines represent the 95% agreement limits.