Author Contributions: Dr Feagan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Feagan, Sandborn, Mittmann, Niv, Vandervoort, Rutgeerts.
Acquisition of data: Sandborn, Bar-Meir, D’Haens, Bradette, Cohen, Dallaire, Ponich, McDonald, Hébuterne, Klvana, Ardizzone, Alexeeva, Rostom, Kiudelis, Spleiss, Gilgen.
Analysis and interpretation of data: Feagan, Sandborn, Mittmann, Bar-Meir, Paré, Wong, Zou, Donner, Rutgeerts.
Drafting of the manuscript: Feagan, Hébuterne, Klvana, Ardizzone, Kiudelis.
Critical revision of the manuscript for important intellectual content: Feagan, Sandborn, Mittmann, Bar-Meir, D’Haens, Bradette, Cohen, Dallaire, Ponich, McDonald, Paré, Niv, Alexeeva, Rostom, Spleiss, Gilgen, Vandervoort, Wong, Zou, Donner, Rutgeerts.
Statistical analysis: Wong, Zou, Donner.
Obtained funding: Sandborn, Klvana, Alexeeva, Spleiss, Rutgeerts.
Administrative, technical, or material support: Feagan, Sandborn, Bar-Meir, D’Haens, Spleiss, Gilgen, Vandervoort.
Study supervision: Feagan, Mittmann, Cohen, Dallaire, Ponich, McDonald, Hébuterne, Paré, Klvana, Ardizzone, Alexeeva, Kiudelis, Vandervoort, Rutgeerts.
Financial Disclosures: Dr Feagan reported receiving grant and research support from Schering-Plough, Otsuka, Milllennium, Tillotts, Abbott, Protein Design Labs, Boehringer-Ingelheim, Novartis, Centocor, Berlex, Synta, Schering Canada, Elan/Biogen, UCB Pharma, BMS, Proctor & Gamble, and Napo Pharma; receiving consulting fees from Synta, Millennium, Schering Canada, Celltech, Centocor, Elan/Biogen, Janssen-Ortho, Protein Design Labs, ISIS, Teva Pharmaceuticals, Santarus, Schering-Plough, Bristol-Myers Squibb, Celgene, CombinatorRx Inc, UCB Pharma, Napo Pharma, Abbott, Proctor & Gamble, Osiris, Berlex, AstraZeneca, GeneLogic Inc, Cerimon Pharm, Tioga Pharm, Serono, Genentech, Tillotts Pharma AG, and CombinatoRx Inc; serving on the apeakers bureau of AstraZeneca; and serving on the scientific advisory board of Protein Design Labs, AstraZeneca, Elan/Biogen, Celltech, Synta, Schering Canada, Celgene, and Tillotts Pharma AG. Dr Sandborn reported receiving grants or funding from Abbott Laboratories, Bristol-Meyers Squibb, Centocor, Chemocentryx, Elan Pharmaceuticals Inc, Otsuka American Pharmaceuticals Inc, PDL Biopharma, Procter & Gamble, Prometheus Laboratories, Salix Pharmaceuticals Inc, Schering-Plough, Serono, Shire Pharmaceuticals, Targacept Inc, Techlab Inc, Tillotts Pharma AG, and UCB Pharma (previously Celltech Therapeutics Ltd); receiving consulting fees from GlaxoSmithKline (previously Glaxo Wellcome), Abbott Laboratories (fees paid to the Mayo Clinic), ActoGeniX NV, AGI Therapeutics Inc, Ajinomoto Pharmaceuticals, Alba Therapeutics, Alizyme plc, Alza, Amgen Inc, Ardea Biosciences, Aspreva Pharmaceuticals, AstraZeneca, Atrix Laboratories Inc (acquired by QLT in 2004), Avidia Inc, Berlex, Bexel Pharmaceuticals Inc, BioBalance, Boehringer-Ingelheim Inc, Bristol Meyers Squibb, Celegene, Celltech (acquired by UCB Pharma in 2004) (fees paid to the Mayo Clinic), Centocor (fees paid to the Mayo Clinic), Cerimon Pharmaceutical Inc, Chemocentryx, CombinatoRx Inc, CoMentis, Corautus Genetics, Cosmo Technologies Ltd, CuraGen, Effective Pharmaceuticals Inc, Eisai Medical Research Inc, Elan Pharmaceuticals Inc, Enteromedics, Enzo Therapeutics Inc, Eurand, FlexPharm Ltd (previously named Enterotech), Genencor International, Genentech, H3 Pharma (name changed to Debiopharm SA in 2005), Hoffman LaRoche Inc (Roche), Hutchison Medipharma Ltd, Inflabloc Pharmaceuticas (previously named Pharmadigm Inc), Inotek Pharmaceutical, ISIS Pharmaceuticals, Jacobus Pharmaceutical Co, Johnson & Johnson Pharmaceutical Research & Development, LigoCyte Pharmaceuticals, McNeil Consumer and Specialty Pharmaceuticals, Medarex Inc, Merck Research Laboratories, Millennium Pharmaceuticals Inc, Nisshin Kyorin Pharmaceutical Co Ltd, Novartis, NPS Pharmaceuticals, Ocera Therapeutics Inc (previously named Renovia Inc), Ono Pharma USA, Otsuka American Pharmaceuticals Inc, PDL Biopharma (previously named Protein Design Labs) (fees paid to the Mayo Clinic), Pfizer, Procter & Gamble (fees paid to the Mayo Clinic), Prometheus Laboratories, Renovis Inc, Salix Pharmaceuticals Inc, Sangstat (acquired by Genzyme in 2003), Schering-Plough, Serono Inc, Shire Pharmaceuticals, Synta Pharmaceuticals, Targacept, Teva Pharmaceuticals, Therakos, Tioga Pharmaceuticals, UCB Pharma (fees paid to the Mayo Clinic), Vela Pharmaceuticals Inc, and ViaCell Inc; and receiving honoraria for speaking at continuing medical education events indirectly sponsored by Abbott Laboratories, Axcan Pharmaceuticals, AstraZeneca, Centocor, Elan Pharmaceuticals Inc, Falk Pharma, Otsuka American Pharmaceuticals Inc, PDL Biopharma, Procter & Gamble, Prometheus Laboratories, Salix Pharmaceuticals Inc, Schering-Plough, Shire Pharmaceuticals, and UCB Pharma. Dr Mittmann reported receiving product development consultancy fees from Tillotts Pharma AG. Dr Bar-Meir reported receiving consulting fees from Tillotts Pharma AG. Dr Rostom reported receiving consulting fees from Novartis and Bayer and an unrestricted educational grant from ALBA Therapeutics. Mr Spleiss reported having employee equity ownership in Tillotts Pharma AG. Dr Rutgeerts reported receiving consulting fees from Centocor, Schering-Plough, UCB Abbott, Elan-Biogen, PDL, Avidia, Bristol-Myers Squibb, Millennium, and Tillotts; lecture fees from Centocor, Schering-Plough, UCB, Abbott, and Elan-Biogen; and grant support from Centocor, Schering-Plough, Abbott, and UCB. Drs D’Haens, Bradette, Cohen, Dallaire, Ponich, McDonald, Kiudelis, Hebuterne, Paré, Klvana, Niv, Ardizzone, Alexeeva, and Rostom were site investigators and were compensated for performing clinical measurements. No other financial disclosures were reported.
Funding/Support: This study was funded by Tillotts Pharma.
Role of the Sponsor: The trial was designed by the academic investigators in collaboration with representatives of Tillotts, and representatives of Tillotts reviewed and approved the final version of the manuscript.
Data and Safety Monitoring Board:University of Health Sciences Center, Denver, Colorado: J. Singleton; Charité-Universitätsmedizin Berlin: H. Lochs; Wolfson Institute of Preventative Medicine, London, UK: J. Cuzick. Data Coordinating Center:Robarts Clinical Trials, Robarts Research Institute, The University of Western Ontario, London, Ontario: F. Babar, B. Bergman, M. Bertin, T. Clayton, M. Hammond, M. Hopkins, L. Jensen, E. Karugu, L. Liddiard, F. Livingstone, M. Mathers, C. Mueller, S. Nelson, J. Rémillard, I. Ruocco, B. Sarazin, B. Sharpe, L. Smith, H. Sun, K. Toulouse. Participating Investigators:Atlanta Gastroenterology Associates, Atlanta, Georgia: D. Wolf, M. Monroe; Carle Clinic Association, Urbana, Illinois: E. Greenberg, V. Carlton; Cleveland Clinic Foundation, Cleveland, Ohio: D. Seidner, S. Zurc; Clinical Research Institute of Michigan, Chesterfield: R. Fogel, A. Leyson-Fiel; Health Sciences Centre, Calgary, Alberta: R. Panaccione, A. Daye; Health Sciences Centre, Edmonton, Alberta: R. Fedorak, C. McCabe-Woodrow; Health Sciences Centre, Winnipeg, Manitoba: C. Bernstein, T. Rawsthorne; Hôpital Maisonneuve-Rosemont, Montreal, Québec: G. Aumais, L. Henri; Hôpital St-Sacrement, Québec City, Québec: P. Paré, S. Rousseau; Hôtel Dieu de Levis, Levis, Québec: R. Bourdages, M. Berberi; Hotel Dieu Hospital, Kingston, Ontario: W. Depew, D. Brady; Jewish General Hospital, Montreal, Québec: A. Cohen, N. Desjardins; LAIR Centre, Vancouver, British Coumbia: F. Anderson, I. Wong; London Health Sciences Centre South Street Campus, London Ontario: T. Ponich, P. Walton-Mennill; London Health Sciences Centre University Campus, London, Ontario: J. McDonald, W. McCaw; Long Island Clinical Research Associates, Great Neck, New York: S. Katz, M. Mustac; Mayo Clinical Rochester, Minnesota: W. Sandborn, R. Jeche; Montreal General Hospital, Montreal, Québec: G. Wild, N. Pellerin; Mount Sinai Hospital, Toronto, Ontario: H. Steinhart, S. Mikolainis; Pavillon-Hôtel-Dieu de Québec CHUQ, Québec City, Québec: M. Bradette, S. Lepire; Pavillon St-François d’Assise CHUQ, Québec City, Québec: C. Dallaire, F. Bernard; Royal Alexandra Hospital, Edmonton, Albaerta: R. Bailey, D. Meyer; Royal Victoria Hospital, Montreal, Québec: A. Bitton, M. Bernier; Saint John Regional Hospital, Saint John, New Brunswick: A. Cockeram, H. Long; St Joseph's Health Centre, London, Ontario: R. Sy, L. Moyer; St Michael's Hospital, Toronto, Ontario: J. Baker, G. Stewart; St Paul's Hospital GI Research, Vancouver, British Columbia: R. Enns, S. Patterson; Sunnybrook & Women's College Health Science Centre, Toronto, Ontario: F. Saibil, M. Morgan; The Ottawa Hospital-Civic Campus, Ottawa, Ontario: A. Rostom, P. Waddell; University of Chicago Medical Center, Chicago, Illinois: S. Hanauer, H. Brenner; University of Kentucky Medical Branch, Lexington: T. Winter, J. Reynolds; University of North Carolina at Chapel Hill: K. Isaacs; D. Walkup; University of Texas Medical Branch, Galveston: J. Sellin, J. Hirsch; Victoria General Hospital QEII Health Sciences Centre, Halifax, Nova Scotia: D. MacIntosh, C. Kelly; Albrecht-Ludwigs-University, Freiburg, Germany: J. Rasenack, I. Borsukiewicz-Krupa; Internistische Praxis, Medizin, Berlin, Germany: H.-J. Kramm, I. Borsukiewicz-Krupa; Barzilai Medical Center, Ashkelon, Israel: M. Faschik, I. Rosen-Leibowitz; CHU de Grenoble, Grenoble, France: B. Bonaz, S. Zachayus; District Hospital, Usti nad Orlici, Czech Republic: L. Gabalec. L. Pribylova; District Hospital, Ceske Budejovice, Czech Republic: O. Shonova, L. Pribylova; Faculty Hospital, Prague, Czech Republic: J. Benes, L. Pribylova; Hadassah University Hospital, Jerusalem, Israel: E. Goldin, I. Rosen-Leibowitz; Heilig Hartziekenhuis, Roeselare, Belgium: F. Baert, W. Walravens; Hillel Yaffe Medical Center, Hadera, Israel: Z. Fireman, I. Rosen-Leibowitz; Hôpital Civil, Strasbourg, France: D. Vetter, S. Zachayus; Hôpital Saint Antoine, Paris, France: J. P. Gendre, S. Zachayus; Hospital Nord, Marseille, France: J.-C. Grimaud, S. Zachayus; Imelda Ziekenhuis, Bonheiden, Belgium: G. D’Haens, K. Lauwers; Internistische Gemeinschaftspraxis, Rödermark-Oberroden, Germany: S. Orlemann, I. Borsukiewicz-Krupa; Kaunas Medical University Clinics, Kaunas, Lithuania: G. Kiudelis, L. Didziapetriene; Klinikum der Universität Regensburg, Regensburg, Germany: H. Herfarth, I. Borsukiewicz-Krupa; Klinikum Mannheim, Mannheim, Germany: U. Böcker, I. Borsukiewicz-Krupa; Masaryk Hospital, Usti nad Labem, Czech Republic: J. Stehlik, L. Pribylova; Medizinische Hochschule Hannover, Hannover, Germany: M. Manns, I. Borsukiewicz-Krupa; Medizinische Universitäts, Erlangen, Germany: D. Raithel, I. Borsukiewicz-Krupa; Ospedale G. B Morgagni, Forli, Italy: D. Valpiani, P. Zamboni; Ospedale Luigi Sacco, Milan, Italy: S. Ardizzone, P. Zamboni; Ospedale Nuovo, Imola, Italy: C. Brignola, P. Zamboni; Ospedale Santissima Annunziata, Cento, Italy: G. Zoli, P. Zamboni; Policlinico S. Orsola Malpighi, Bologna, Italy: A. Belluzzi, T. Perrone; Rabin Medical Center Beilinson Campus, Petah Tiqwa, Israel: Y. Niv, O. BenShitrit; Ranbam Medical Center, Haifa, Israel: A. Eliakim, I. Rosen-Leibowitz; Soroka University Medical Center, Beer Sheva, Israel: A. Fich, I. Rosen-Leibowitz; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel: I. Dotan, I. Rosen-Leibowitz; The Chaim Sheba Medical Center, Tel Hashomer, Israel: A. Lang, I. Rosen-Leibowitz; The Edith Wolfson Medical Center, Holon, Israel: Y. Avni, I. Rosen-Leibowitz; ULB Hôpital Erasme, Brussels, Belgium: A. Van Gossum, W. Walravens; University Hospital, Ostrava, Czech Republic: P. Klvana, L. Pribylova; University Hospital, Pilzen, Czech Republic: J. Kozeluhova, L. Pribylova; University of Nice Sophia Antipolis, Nice, France: X. Hébuterne; UZ Gashuisberg, Leuven, Belgium: P. Rutgeerts, K. Lauwers; Vilnius University Hospital, Vilnius, Lithuania: A. Irnius, L Didziapetriene; Western Galilee Hospital, Nahariya, Israel: R. Reshef, I. Rosen-Leibowitz; Clinical Hospital, #33, Nizhyn Novgorod, Russia : O. Alexeeva, S. Krishtopenko, E. Galperin, O. Chertkova; Military Medical Academy, St. Petersburg, Russia : V. Grinevich, I. Gubonina, A. Pershko; St. Petersburg Medical Academy, St. Petersburg, Russia : A. Baranovsky, O. Shchukina, E. Kondrashina; Medical Academy, St. Petersburg, Russia : V. Simanenkov, E. Poroshina, O. Solovyeva; Moscow Regional Research Clinical Institute, Moscow, Russia : E. Belousova, O. Kuzmina, I. Domareva; Regional Clinical Hospital, Yaroslaval, Russia : O. Khrustalev, O. Okhapkina, S. Tsybulko.