FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 331:836-841 September 29, 1994 Number 13 Next

	Full Text Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Corticosteroids are the most efficacious drugs for inducing remission in active Crohn's disease, but their benefits are frequently offset by serious side effects. Budesonide is a corticosteroid with high topical antiinflammatory activity but low systemic activity because of extensive hepatic metabolism. We investigated the efficacy and safety of an oral controlled-ileal-release preparation of budesonide in patients with active Crohn's disease involving the ileum or ileum and proximal colon.

Methods In a double-blind, multicenter trial, 258 patients were randomly assigned to receive placebo or one of three doses of budesonide -- 3, 9, or 15 mg daily. The primary outcome measure was clinical remission, as defined by a score of 150 or less on the Crohn's disease activity index.

Results After eight weeks of treatment, remission occurred in 51 percent of the patients in the group receiving 9 mg of budesonide (95 percent confidence interval, 39 to 63 percent), 43 percent of those receiving 15 mg (95 percent confidence interval, 31 to 55 percent), and 33 percent of those receiving 3 mg (95 percent confidence interval, 21 to 44 percent), as compared with 20 percent of those receiving placebo (P<0.001, P = 0.009, and P = 0.13, respectively). Improvements in the quality of life, as measured by the patients' responses to the inflammatory bowel disease questionnaire, parallelled these remission rates. Location of disease, prior surgical resection, and previous use of corticosteroids did not affect the outcome. A total of 119 patients (46 percent) were withdrawn from the study before the trial ended, 96 because of insufficient therapeutic effects, 13 because of adverse reactions, and 10 because of noncompliance. Budesonide caused a dose-related reduction in basal and corticotropin-stimulated plasma cortisol concentrations but was not associated with clinically important corticosteroid-related symptoms or other toxic effects.

Conclusions In an eight-week trial, an oral controlled-release preparation of budesonide at an optimal daily dose of 9 mg was well tolerated and effective against active Crohn's disease of the ileum and proximal colon.

Source Information

From the Department of Medicine, University of Toronto, Toronto (G.R.G.); the Departments of Medicine and Epidemiology and Biostatistics, University of Western Ontario, London (B.G.F.); the Department of Medicine, University of Montreal, Montreal (F.M.); the Department of Medicine, University of Calgary, Calgary, Alta. (L.R.S.); the Department of Medicine, University of Alberta, Edmonton (A.B.R.T.); the Department of Medicine, Dalhousie University, Halifax, N.S. (C.N.W.); and the Departments of Clinical Research and Development and Biostatistics and Data Processing, Astra Draco, Lund, Sweden (L.-G.N., T.P.). Members of the study group are listed in the Appendix.

Address reprint requests to Dr. Greenberg at Mount Sinai Hospital, 600 University Ave., Rm. 445, Toronto, ON M5G 1X5, Canada.

Full Text of this Article

This article has been cited by other articles:

• Feagan, B. G., Sandborn, W. J., Mittmann, U., Bar-Meir, S., D'Haens, G., Bradette, M., Cohen, A., Dallaire, C., Ponich, T. P., McDonald, J. W. D., Hebuterne, X., Pare, P., Klvana, P., Niv, Y., Ardizzone, S., Alexeeva, O., Rostom, A., Kiudelis, G., Spleiss, J., Gilgen, D., Vandervoort, M. K., Wong, C. J., Zou, G. Y., Donner, A., Rutgeerts, P. (2008). Omega-3 Free Fatty Acids for the Maintenance of Remission in Crohn Disease: The EPIC Randomized Controlled Trials. JAMA 299: 1690-1697 [Abstract] [Full Text]  
• Forbes, A (2007). Crohn's disease or abdominal tuberculosis?. Gut 56: 1757-1758 [Full Text]  
• Travis, S P L, Stange, E F, Lemann, M, Oresland, T, Chowers, Y, Forbes, A, D'Haens, G, Kitis, G, Cortot, A, Prantera, C, Marteau, P, Colombel, J-F, Gionchetti, P, Bouhnik, Y, Tiret, E, Kroesen, J, Starlinger, M, Mortensen, N J, for the European Crohn's and Colitis Organisation, (2006). European evidence based consensus on the diagnosis and management of Crohn's disease: current management. Gut 55: i16-i35 [Abstract] [Full Text]  
• Tumulty, J. W., Broussard, J. D., Steiner, J. M., Peterson, M. E., Williams, D. A. (2004). Clinical Effects of Short-Term Oral Budesonide on the Hypothalamic-Pituitary-Adrenal Axis in Dogs With Inflammatory Bowel Disease. Journal of the American Animal Hospital Association 40: 120-123 [Abstract] [Full Text]  
• Jung, D, Fantin, A C, Scheurer, U, Fried, M, Kullak-Ublick, G A (2004). Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor. Gut 53: 78-84 [Abstract] [Full Text]  
• Hofer, K. N (2003). Oral Budesonide in the Management of Crohn's Disease. The Annals of Pharmacotherapy 37: 1457-1464 [Abstract] [Full Text]  
• Thiesen, A, Wild, G E, Tappenden, K A, Drozdowski, L, Keelan, M, Thomson, B K A, McBurney, M I, Clandinin, M T, Thomson, A B R (2003). The locally acting glucocorticosteroid budesonide enhances intestinal sugar uptake following intestinal resection in rats. Gut 52: 252-259 [Abstract] [Full Text]  
• Gassull, M A, Fernandez-Banares, F, Cabre, E, Papo, M, Giaffer, M H, Sanchez-Lombrana, J L, Richart, C, Malchow, H, Gonzalez-Huix, F, Esteve, M (2002). Fat composition may be a clue to explain the primary therapeutic effect of enteral nutrition in Crohn's disease: results of a double blind randomised multicentre European trial. Gut 51: 164-168 [Abstract] [Full Text]  
• Hanauer, S B (2002). New steroids for IBD: progress report. Gut 51: 182-183 [Full Text]  
• Campieri, M (2002). New steroids and new salicylates in inflammatory bowel disease: a critical appraisal. Gut 50: iii43-46 [Abstract] [Full Text]  
• Cortot, A, Colombel, J-F, Rutgeerts, P, Lauritsen, K, Malchow, H, Hamling, J, Winter, T, Van Gossum, A, Persson, T, Pettersson, E (2001). Switch from systemic steroids to budesonide in steroid dependent patients with inactive Crohn's disease. Gut 48: 186-190 [Abstract] [Full Text]  
• BORGAONKAR, M R, IRVINE, E J (2000). Quality of life measurement in gastrointestinal and liver disorders. Gut 47: 444-454 [Abstract] [Full Text]  
• Zareie, M., Brattsand, R., Sherman, P. M., McKay, D. M., Perdue, M. H. (1999). Improved Effects of Novel Glucocorticosteroids on Immune-Induced Epithelial Pathophysiology. J. Pharmacol. Exp. Ther. 289: 1245-1249 [Abstract] [Full Text]  
• Thomsen, O. O., Cortot, A., Jewell, D., Wright, J. P., Winter, T., Veloso, F. T., Vatn, M., Persson, T., Pettersson, E., The International Budesonide-Mesalamine Study Grou, (1998). A Comparison of Budesonide and Mesalamine for Active Crohn's Disease. NEJM 339: 370-374 [Abstract] [Full Text]  
• del Rosario, J. F., Orenstein, S. R., Neigut, D. A., Giarrusso, V., Wolfson, N., Kocoshis, S. A. (1998). Retrospective Analysis of Alternate-Day Predn'isone Maintenance Therapy for Crohn's Disease. CLIN PEDIATR 37: 413-419 [Abstract]  
• Wyllie, R., Sarigol, S. (1998). The Treatment of Inflammatory Bowel Disease in Children. CLIN PEDIATR 37: 421-425  
• Gross, V, Andus, T, Ecker, K W, Raedler, A, Loeschke, K, Plauth, M, Rasenack, J, Weber, A, Gierend, M, Ewe, K, Scholmerich, J, Budesonide Study Group, (1998). Low dose oral pH modified release budesonide for maintenance of steroid induced remission in Crohn's disease. Gut 42: 493-496 [Abstract] [Full Text]  
• Campieri, M, Ferguson, A, Doe, W, Persson, T, Nilsson, L-G, the Global Budesonide Study Group, (1997). Oral budesonide is as effective as oral prednisolone in active Crohn's disease. Gut 41: 209-214 [Abstract] [Full Text]  
• Guyatt, G. H., Naylor, C. D., Juniper, E., Heyland, D. K., Jaeschke, R., Cook, D. J. (1997). Users' Guides to the Medical Literature: XII. How to Use Articles About Health-Related Quality of Life. JAMA 277: 1232-1237 [Abstract]  
• (1997). Controlled-release budesonide in Crohn's disease. DTB 35: 30-31 [Abstract] [Full Text]  
• Hanauer, S. B. (1996). Inflammatory Bowel Disease. NEJM 334: 841-848 [Full Text]  
• Feagan, B. G., Rochon, J., Fedorak, R. N., Irvine, E. J., Wild, G., Sutherland, L., Steinhart, A. H., Greenberg, G. R., Gillies, R., Hopkins, M., Hanauer, S. B., McDonald, J. W.D., The North American Crohn's Study Group Investigato, (1995). Methotrexate for the Treatment of Crohn's Disease. NEJM 332: 292-297 [Abstract] [Full Text]  
• Forgacs, I. (1995). Recent Advances: Clinical gastroenterology. BMJ 310: 113-116 [Full Text]  
• (1994). ORAL BUDESONIDE FOR CROHN'S DISEASE. JWatch General 1994: 1-1 [Full Text]  
• Rutgeerts, P., Lofberg, R., Malchow, H., Lamers, C., Olaison, G., Jewell, D., Danielsson, A., Goebell, H., Thomsen, O. O., Lorenz-Meyer, H., Hodgson, H., Persson, T., Seidegard, C. (1994). A Comparison of Budesonide with Prednisolone for Active Crohn's Disease. NEJM 331: 842-845 [Abstract] [Full Text]  
• Sachar, D. B. (1994). Budesonide for Inflammatory Bowel Disease -- Is It a Magic Bullet?. NEJM 331: 873-874 [Full Text]