Endoscopic improvement of mucosal lesions in patients with moderate to severe ileocolonic Crohn's disease following treatment with certolizumab pegol
- Xavier Hébuterne1,2,
- Marc Lémann2,3,
- Yoram Bouhnik2,4,
- Olivier Dewit5,
- Jean-Louis Dupas2,6,
- Michael Mross7,
- Geert D'Haens8,
- Krassimir Mitchev9,
- Étienne Ernault9,
- Séverine Vermeire10,
- Hedia Brixi-Benmansour2,11,
- Tom G Moreels12,
- Jean-Yves Mary2,13,
- Philippe Marteau2,14,
- Jean-Frédéric Colombel2,15
- 1CHU Nice, INSERM ERI-21, EA4319, University of Nice Sophia-Antipolis, Nice, France
- 2Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID)
- 3Hôpital Saint Louis, Paris, France
- 4Hôpital Beaujon, Clichy, France
- 5UCL Saint Luc, Brussels, Belgium
- 6CHU Amiens, Amiens, France
- 7Special Medical Practice, Berlin, Germany
- 8Academic Medical Centre, Amsterdam, The Netherlands and Imelda General Hospital, Bonheiden, Belgium
- 9UCB Pharma, Braine L'Alleud, Belgium
- 10University Hospital Gasthuisberg, Leuven, Belgium
- 11CHU Reims, Reims, France
- 12Antwerp University Hospital, Antwerp, Belgium
- 13INSERM U717, Université Paris 7, Paris, France
- 14Hôpital Lariboisière, Université Paris 7, Paris, France
- 15CHU Lille, INSERM-CIC9301 and Universite Lille Nord de France, Lille, France
- Correspondence to Professor Xavier Hébuterne, Department of Gastroenterology and Nutrition, Archet Hospital, 151, Route Saint Antoine de Ginestière, CHU de Nice, 06202 Nice Cedex 03, France;
Contributors The study protocol was developed collaboratively by the authors and the clinical development team at UCB. XH, ML and JFC led the development of each draft; all other authors critically reviewed each draft and contributed to the revision process. Data analysis was conducted at UCB under the direction of EE according to a statistical analysis plan; these analyses were critically reviewed by JYM, XH and JFC who directed the execution of additional analyses. All authors approved the final version of the manuscript. Assistance provided by the medical writer included: working with the lead authors to develop drafts, incorporating input from coauthors, managing the administrative aspects of the process and overseeing the copyediting, formatting and styling of the manuscript, figures and tables.
- Revised 27 February 2012
- Accepted 29 February 2012
- Published Online First 23 April 2012
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.
Marc Lémann died on 26 August 2010. We remember our esteemed colleague and recognise his contributions to this manuscript and to advancing the understanding and treatment of Crohn's disease.
Funding The MUSIC study (NCT00297648) was funded by UCB Pharma.
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.
Ethics approval The protocol, all protocol amendments, and the informed consent document were reviewed and approved by an independent ethics committee or institutional review board at each site. All patients gave their informed consent to participate in the study before any study-related procedures were performed.
Provenance and peer review Not commissioned; externally peer reviewed.
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