Study Comparing Cyclosporine With Infliximab in Steroid-refractory Severe Attacks of Ulcerative Colitis

Summary

PHASE: IV TYPE OF STUDY: With direct benefit. DESCRIPTIVE: Multicenter, randomized, open label study. INCLUSION CRITERIA: Steroid-refractory ulcerative colitis. OBJECTIVES: To compare the efficacy of cyclosporine with infliximab in steroid- refractory attacks of ulcerative colitis. STUDY TREATMENTS:Cyclosporine 2mg/kg/day intravenous(IV)for 7days then Neoral 4mg/kg/day orally for 3 months. Infliximab 5mg/kg at Weeks 0, 2 and 6. NUMBER OF PATIENTS: 50 patients in each group i.e. a total of 100 patients. INCLUSION PERIOD: 24 months. STUDY DURATION: 27 months. MAIN EVALUATION CRITERIA: Clinical response at D7 according to the Lichtiger Index score AND Clinical Remission at D98 according to the Mayo Disease Activity Index score SECONDARY EVALUATION CRITERIA: Clinical remission at D98 (according to the Mayo Disease Activity Index score) Endoscopic response Colectomy rate Tolerance

Timeline

Start

2007-06

Primary completion

2007-06

Completion

2010-10

Publications

• Background EDWARDS FC, TRUELOVE SC. THE COURSE AND PROGNOSIS OF ULCERATIVE COLITIS. Gut. 1963 Dec;4(4):299-315. doi: 10.1136/gut.4.4.299.
• Background Truelove SC, Willoughby CP, Lee EG, Kettlewell MG. Further experience in the treatment of severe attacks of ulcerative colitis. Lancet. 1978 Nov 18;2(8099):1086-8. doi: 10.1016/s0140-6736(78)91816-0.
• Background D'Haens G, Lemmens L, Geboes K, Vandeputte L, Van Acker F, Mortelmans L, Peeters M, Vermeire S, Penninckx F, Nevens F, Hiele M, Rutgeerts P. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology. 2001 May;120(6):1323-9. doi: 10.1053/gast.2001.23983.
• Background Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, Michelassi F, Hanauer S. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994 Jun 30;330(26):1841-5. doi: 10.1056/NEJM199406303302601.
• Background Van Assche G, D'Haens G, Noman M, Vermeire S, Hiele M, Asnong K, Arts J, D'Hoore A, Penninckx F, Rutgeerts P. Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Gastroenterology. 2003 Oct;125(4):1025-31. doi: 10.1016/s0016-5085(03)01214-9.
• Background Arts J, D'Haens G, Zeegers M, Van Assche G, Hiele M, D'Hoore A, Penninckx F, Vermeire S, Rutgeerts P. Long-term outcome of treatment with intravenous cyclosporin in patients with severe ulcerative colitis. Inflamm Bowel Dis. 2004 Mar;10(2):73-8. doi: 10.1097/00054725-200403000-00002.
• Background Actis GC, Bresso F, Astegiano M, Demarchi B, Sapone N, Boscaglia C, Rizzetto M. Safety and efficacy of azathioprine in the maintenance of ciclosporin-induced remission of ulcerative colitis. Aliment Pharmacol Ther. 2001 Sep;15(9):1307-11. doi: 10.1046/j.1365-2036.2001.01019.x.
• Background Cohen RD, Stein R, Hanauer SB. Intravenous cyclosporin in ulcerative colitis: a five-year experience. Am J Gastroenterol. 1999 Jun;94(6):1587-92. doi: 10.1111/j.1572-0241.1999.01149.x.
• Background Ardizzone S, Maconi G, Russo A, Imbesi V, Colombo E, Bianchi Porro G. Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut. 2006 Jan;55(1):47-53. doi: 10.1136/gut.2005.068809. Epub 2005 Jun 21.
• Background Shibolet O, Regushevskaya E, Brezis M, Soares-Weiser K. Cyclosporine A for induction of remission in severe ulcerative colitis. Cochrane Database Syst Rev. 2005 Jan 25;2005(1):CD004277. doi: 10.1002/14651858.CD004277.pub2.
• Background Jarnerot G, Hertervig E, Friis-Liby I, Blomquist L, Karlen P, Granno C, Vilien M, Strom M, Danielsson A, Verbaan H, Hellstrom PM, Magnuson A, Curman B. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. 2005 Jun;128(7):1805-11. doi: 10.1053/j.gastro.2005.03.003.
• Background Su C, Salzberg BA, Lewis JD, Deren JJ, Kornbluth A, Katzka DA, Stein RB, Adler DR, Lichtenstein GR. Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis. Am J Gastroenterol. 2002 Oct;97(10):2577-84. doi: 10.1111/j.1572-0241.2002.06026.x.
• Background Gornet JM, Couve S, Hassani Z, Delchier JC, Marteau P, Cosnes J, Bouhnik Y, Dupas JL, Modigliani R, Taillard F, Lemann M. Infliximab for refractory ulcerative colitis or indeterminate colitis: an open-label multicentre study. Aliment Pharmacol Ther. 2003 Jul 15;18(2):175-81. doi: 10.1046/j.1365-2036.2003.01686.x.
• Background Kohn A, Prantera C, Pera A, Cosintino R, Sostegni R, Daperno M. Infliximab in the treatment of severe ulcerative colitis: a follow-up study. Eur Rev Med Pharmacol Sci. 2004 Sep-Oct;8(5):235-7.
• Background Eidelwein AP, Cuffari C, Abadom V, Oliva-Hemker M. Infliximab efficacy in pediatric ulcerative colitis. Inflamm Bowel Dis. 2005 Mar;11(3):213-8. doi: 10.1097/01.mib.0000160803.44449.a5.
• Background Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516.
• Hasskamp J, Meinhardt C, Patton PH, Timmer A. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2025 Feb 27;2(2):CD000478. doi: 10.1002/14651858.CD000478.pub5.
• Laharie D, Bourreille A, Branche J, Allez M, Bouhnik Y, Filippi J, Zerbib F, Savoye G, Vuitton L, Moreau J, Amiot A, Cosnes J, Ricart E, Dewit O, Lopez-Sanroman A, Fumery M, Carbonnel F, Bommelaer G, Coffin B, Roblin X, van Assche G, Esteve M, Farkkila M, Gisbert JP, Marteau P, Nahon S, de Vos M, Lambert J, Mary JY, Louis E; Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives. Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab. Gut. 2018 Feb;67(2):237-243. doi: 10.1136/gutjnl-2016-313060. Epub 2017 Jan 4.
• Laharie D, Bourreille A, Branche J, Allez M, Bouhnik Y, Filippi J, Zerbib F, Savoye G, Nachury M, Moreau J, Delchier JC, Cosnes J, Ricart E, Dewit O, Lopez-Sanroman A, Dupas JL, Carbonnel F, Bommelaer G, Coffin B, Roblin X, Van Assche G, Esteve M, Farkkila M, Gisbert JP, Marteau P, Nahon S, de Vos M, Franchimont D, Mary JY, Colombel JF, Lemann M; Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial. Lancet. 2012 Dec 1;380(9857):1909-15. doi: 10.1016/S0140-6736(12)61084-8. Epub 2012 Oct 10.

Drugs

Indications