Oral budesonide was less effective, less toxic than prednisolone for Crohn disease
ACP J Club. 1995 Jan-Feb;122:14. doi:10.7326/ACPJC-1995-122-1-014
Rutgeerts P, Löfberg R, Malchow H, et al. A comparison of budesonide with prednisolone for active Crohn's disease. N Engl J Med. 1994 Sep 29;331:842-5.
To compare the safety and efficacy of oral controlled-release budesonide with that of prednisolone in patients with active Crohn disease.
10-week randomized, double-blind, placebo-controlled trial.
11 centers in Europe.
176 patients (mean age 36 y 109 women) were ≥ 18 years and had active Crohn disease (Crohn disease activity index score ≥ 200) confined to the ileal or ileocecal region. Exclusion criteria were previous ileostomy or small-bowel resection > 100 cm; complications including abscesses, perforations, or fistulas; discontinuation of corticosteroid treatment within the previous 2 weeks; concomitant peptic ulcer or hepatic, renal, cardiovascular, or psychiatric conditions; and need for immediate surgery. 145 (82%) patients completed the study.
Patients were stratified by center and assigned to prednisolone (n = 88) or budesonide (n = 88). Prednisolone was administered at 40 mg/d for 2 weeks, 30 mg/d for 2 weeks, and 25 mg/d for 2 weeks; the dose was decreased by 5 mg/d for each of the remaining 4 weeks. Budesonide was administered at 9 mg/d for 8 weeks and 6 mg/d for the last 2 weeks. All patients took placebo tablets of the "drug" to which they were not assigned. Compliance was assessed by pill counts.
Main outcome measures
Remission (Crohn disease activity index score ≤ 150) and success (decrease of at least 100 units in the score) rates, and adverse effects. Outcomes were assessed at 4, 8, and 10 weeks.
Analysis was by intention to treat. For all 3 assessment times, differences in rates of remission and success did not reach statistical significance (10-wk remission rates are shown in the Table). Over the 10 weeks, a greater mean decrease in the Crohn disease activity index score was noted for the prednisolone group compared with the budesonide group (143 points vs 100 points, P = 0.001). More patients receiving prednisolone had corticosteroid-associated adverse effects than did patients receiving budesonide (P = 0.03) (Table).
Oral budesonide was less effective than prednisolone but had fewer side effects in patients with active Crohn disease.
Source of funding: Astra Draco, Lund, Sweden.
For article reprint: Dr. P. Rutgeerts, University Hospital, B-3000 Leuven, Belgium. FAX 32-16-34-4419.
Table. Budesonide vs prednisolone for Crohn disease at 10 weeks*
|Outcomes||Budesonide||Prednisolone||RBR (95% CI)||NNH (CI)|
|Remission||53%||66%||19% (-3 to 37)||Not significant|
|RRR (CI)||NNT (CI)|
|Adverse effects||33%||55%||40% (15 to 58)||5 (3 to 14)|
*RBR = relative benefit reduction. Other abbreviations defined in Glossary; RBR, RRR, NNH, NNT, and CI calculated from data in article.
Numerous immunosuppressors have been used in the treatment of inflammatory bowel disease (IBD). These include azathioprine/6-mercaptopurine (Aza/6-MP), methotrexate, cyclosporine, tacrolimus, and newer compounds such as anti-tumor necrosis factor-α (TNF), anti-CD4 monoclonal antibiodies, and interleukin 10 and 11. These compounds have been used mostly in steroid-resistant, chronic, active IBD. However, none of them appears to provide a cure for the disease. Among the many listed drugs, Aza/6-MP and methotrexate are the only ones used for long-term treatment of IBD. For other drugs, not enough data exist regarding long-term use except for some recent but limited experience with anti-TNF. Controlled trials and meta-analysis have confirmed the benefit of Aza/6-MP in Crohn disease (1). Methotrexate is considered a second-line immunosuppressant for failure or toxicity from Aza/6-MP and is reported to have a 40% success rate compared with a 20% response rate for placebo (2). The general recommendation is continued treatment for 3 to 4 years to prevent relapse from early discontinuation of the drug with monitoring for side effects that can be severe, although uncommon (3). Low-dose cyclosporine was found to be ineffective in Crohn disease. Infliximab (anti-TNF) has been shown in double-blind controlled trials to be effective in Crohn disease. This is the first drug to show an effect in controlled trials on fistulas associated with Crohn disease. However, long-term side effects of this drug need to be evaluated, and further experience is necessary (4).
Joseph J. Nidiry, MD, FACC
Diplomate American Board of Internal Medicine and GastroenterologyWashington, DC, USA
4. Rutgeerts P, D'Haens G, Targan S, et al. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease. Gastroenterology. 1999;117:761-9.