A Comparison of Budesonide with Prednisolone for Active Crohn's Disease
Paul Rutgeerts, Robert Lofberg, Helmut Malchow, Cornelis Lamers, Gunnar Olaison, Derek Jewell, Ake Danielsson, Harald Goebell, Ole Ostergaard Thomsen, Hertwig Lorenz-Meyer, Humphrey Hodgson, Tore Persson, and Cecilia Seidegard
Background Patients with active Crohn's disease are often treatedwith corticosteroids, but the treatment has many side effects.Budesonide is a potent, well-absorbed corticosteroid, but becauseof a high rate of first-pass metabolism in the liver, its systemicbioavailability is low.
Methods We conducted a randomized, double-blind, 10-week trialcomparing the efficacy and safety of an oral controlled-releaseform of budesonide with the efficacy and safety of prednisolonein 176 patients with active ileal or ileocecal Crohn's disease(88 patients in each treatment group). The dose of budesonidewas 9 mg per day for eight weeks and then 6 mg per day for twoweeks. The dose of prednisolone was 40 mg per day for two weeks,after which it was gradually reduced to 5 mg per day duringthe last week.
Results At 10 weeks, 53 percent of the patients treated withbudesonide were in remission (defined as a score 150 on theCrohn's disease activity index), as compared with 66 percentof those treated with prednisolone (P = 0.12). The mean scoreon the Crohn's disease activity index decreased from 275 to175 in the budesonide group and from 279 to 136 in the prednisolonegroup (P = 0.001). Corticosteroid-associated side effects weresignificantly less common in the budesonide group (29 vs. 48patients, P = 0.003). Two patients in the prednisolone grouphad serious complications (one had intestinal perforation andone an abdominal-wall fistula). The mean morning plasma cortisolconcentration was significantly lower in the prednisolone groupthan in the budesonide group after 4 weeks (P<0.001) and8 weeks (P = 0.02) of therapy, but not after 10 weeks.
Conclusions Among patients with active Crohn's disease, bothcontrolled-release budesonide and prednisolone are effectivein inducing remission. In this trial, prednisolone reduced scoreson the Crohn's disease activity index more, whereas with budesonidethere were fewer glucocorticoid-associated side effects andless suppression of pituitary-adrenal function.
Source Information
From the Department of Gastroenterology, Leuven University Hospital, Leuven, Belgium (P.R.); the Department of Gastroenterology, Huddinge University Hospital, Huddinge, Sweden (R.L.); Akademisches Lehrkrankenhaus der Universitat zu Koln, Leverkusen, Germany (H.M.); the Department of Gastroenterology and Hepatology, University Hospital, Leiden, the Netherlands (C.L.); the Department of Gastroenterology, University Hospital, Linkoping, Sweden (G.O.); the Gastroenterology Unit, Radcliffe Infirmary, Oxford, United Kingdom (D.J.); the Medical Department, University Hospital, Umea, Sweden (A.D.); Medizinische Klinik und Poliklinik der Universitat Essen, Essen, Germany (H.G.); Medical Department C, Herlev University Hospital, Herlev, Denmark (O.O.T.); Stadtisches Krankenhaus Friedrichshafen, Friedrichshafen, Germany (H.L.-M.); Hammersmith Hospital, London (H.H.); and the Departments of Biostatistics and Data Processing (T.P.) and Clinical Research and Development (C.S.), Astra Draco, Lund, Sweden.
Address reprint requests to Dr. Rutgeerts at University Hospital, B-3000 Leuven, Belgium.
Forbes, A
(2007). Crohn's disease or abdominal tuberculosis?. Gut
56: 1757-1758
[Full Text]
Hockenbery, D. M., Cruickshank, S., Rodell, T. C., Gooley, T., Schuening, F., Rowley, S., David, D., Brunvand, M., Berryman, B., Abhyankar, S., Bouvier, M., McDonald, G. B., for the orBec GVHD Study Group,
(2007). A randomized, placebo-controlled trial of oral beclomethasone dipropionate as a prednisone-sparing therapy for gastrointestinal graft-versus-host disease. Blood
109: 4557-4563
[Abstract][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]
Gasche, C, Grundtner, P
(2005). Genotypes and phenotypes in Crohn's disease: do they help in clinical management?. Gut
54: 162-167
[Full Text]
Kirwan, J R, Hallgren, R, Mielants, H, Wollheim, F, Bjorck, E, Persson, T, Book, C, Bowman, S, Byron, M, Cox, N, Field, M, Kanerud, L, Leirisalo-Repo, M, Malaise, M, Mohammad, A, Palmer, R, Petersson, I F, Ringertz, B, Sheldon, P, Simonsson, M, Snowden, N, Van den Bosch, F
(2004). A randomised placebo controlled 12 week trial of budesonide and prednisolone in rheumatoid arthritis. Ann Rheum Dis
63: 688-695
[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]
Bonderup, O K, Hansen, J B, Birket-Smith, L, Vestergaard, V, Teglbjaerg, P S, Fallingborg, J
(2003). Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis. Gut
52: 248-251
[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]
Thiesen, A., Wild, G. E., Keelan, M., Clandinin, M. T., Thomson, A. B. R.
(2003). Locally and systemically active glucocorticosteroids modify intestinal absorption of sugars in rats. J. Appl. Physiol.
94: 583-590
[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]
NUGENT, S G, KUMAR, D, RAMPTON, D S, EVANS, D F
(2001). Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs. Gut
48: 571-577
[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]
Feagan, B. G., Fedorak, R. N., Irvine, E. J., Wild, G., Sutherland, L., Steinhart, A. H., Greenberg, G. R., Koval, J., Wong, C. J., Hopkins, M., Hanauer, S. B., McDonald, J. W.D., The North American Crohn's Study Group Investigato,
(2000). A Comparison of Methotrexate with Placebo for the Maintenance of Remission in Crohn's Disease. NEJM
342: 1627-1632
[Abstract][Full Text]
Rampton, D. S
(1999). Regular review: Management of Crohn's disease. BMJ
319: 1480-1485
[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]
(1994). ORAL BUDESONIDE FOR CROHN'S DISEASE. JWatch General
1994: 1-1
[Full Text]
Greenberg, G. R., Feagan, B. G., Martin, F., Sutherland, L. R., Thomson, A., Williams, C. N., Nilsson, L.-G., Persson, T., The Canadian Inflammatory Bowel Disease Study Grou,
(1994). Oral Budesonide for Active Crohn's Disease. NEJM
331: 836-841
[Abstract][Full Text]
Sachar, D. B.
(1994). Budesonide for Inflammatory Bowel Disease -- Is It a Magic Bullet?. NEJM
331: 873-874
[Full Text]
150 on the Crohn's disease activity index), as compared with 66 percent of those treated with prednisolone (P = 0.12). The mean score on the Crohn's disease activity index decreased from 275 to 175 in the budesonide group and from 279 to 136 in the prednisolone group (P = 0.001). Corticosteroid-associated side effects were significantly less common in the budesonide group (29 vs. 48 patients, P = 0.003). Two patients in the prednisolone group had serious complications (one had intestinal perforation and one an abdominal-wall fistula). The mean morning plasma cortisol concentration was significantly lower in the prednisolone group than in the budesonide group after 4 weeks (P<0.001) and 8 weeks (P = 0.02) of therapy, but not after 10 weeks. 
Previous
