Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Oral budesonide was effective for Crohn disease

ACP J Club. 1995 Jan-Feb;122:15. doi:10.7326/ACPJC-1995-122-1-015

Related Content in this Issue
• Companion Abstract and Commentary: Oral budesonide was less effective, less toxic than prednisolone for Crohn disease


Source Citation

Greenberg GR, Feagan BG, Martin F, et al., and the Canadian Inflammatory Bowel Disease Study Group. Oral budesonide for active Crohn's disease. N Engl J Med. 1994 Sep 29;331:836-41.


Abstract

Objective

To evaluate the efficacy and safety of oral budesonide in patients with active Crohn disease.

Design

8-week randomized, double-blind, placebo-controlled trial.

Setting

27 centers in Canada.

Patients

258 patients (age range 18 to 66 y, 161 women) were ≥ 18 years and had active Crohn disease (Crohn disease activity index score ≥ 200) involving the ileum or ileum and colon and not extending beyond the hepatic flexure. Patients were ineligible if they had a previous ileostomy, severe disease requiring imminent surgery, diabetes mellitus, active infection, peptic ulcer disease, cancer, cardiac or hepatic diseases, or were pregnant or breast-feeding. 139 (54%) patients completed the study.

Intervention

Patients were stratified by treatment center and by whether they had received corticosteroid treatment for > 2 weeks in the preceding year, and were allocated to budesonide in doses of 3 mg/d (n = 67), 9 mg/d (n = 61), or 15 mg/d (n = 64) or to placebo (n = 66). After 8 weeks, the dose for patients receiving 9 or 15 mg was reduced to 6 mg, and patients receiving 3 mg were given placebo. At 2, 4, 8, and 10 weeks, patients had a physical examination and completed questionnaires. Compliance was assessed by pill counts.

Main outcome measures

Remission rates (Crohn disease activity index score ≤ 150), changes in the quality of life, and adverse events.

Main results

Analysis was by intention to treat. At 8 weeks, remission occurred in more budesonide recipients (9 and 15 mg/d) than placebo recipients (P < 0.001 for 9 mg/d and P = 0.005 for 15 mg/d) (Table). Remission rates in the budesonide, 3 mg/d group did not differ from placebo (P = 0.13). Patients receiving budesonide, 9 mg or 3 mg, had a greater mean decrease in Crohn disease activity index scores than did those receiving placebo (121 points and 63 points vs 21 points; P < 0.001 and P = 0.02, respectively). Quality-of-life scores were higher among patients receiving budesonide, 9 mg or 15 mg, compared with placebo recipients (P < 0.001 and P = 0.012, respectively). 215 patients had 744 adverse events (dyspepsia, nausea, and corticosteroid-associated events). The difference in number of adverse events among the 4 groups was not statistically significant.

Conclusion

Oral budesonide, 9 mg/d, was optimally effective and safe in achieving remission and improved quality of life in patients with active Crohn disease.

Source of funding: Astra Draco, Lund, Sweden.

For article reprint: Dr. G.R. Greenberg, Mount Sinai Hospital, 600 University Avenue, Room 445, Toronto, Ontario M5G 1X5, Canada.


Table. Budesonide, 9 mg or 15 mg daily vs placebo for remission of Crohn disease at 8 weeks*

Comparison Event rates RBI (95% CI) NNT (CI)
Budesonide, 9 mg/d vs placebo 51% vs 20% 158% (53 to 349) 3 (2 to 7)
Budesonide, 15 mg/d vs placebo 43% vs 20% 118% (26 to 285) 4 (3 to 14)

*Abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article.


Updated Commentary

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 clinical experience is necessary (4).

Joseph J. Nidiry, MD, FACC
Diplomate American Board of Internal Medicine and GastroenterologyWashington, DC, USA


References

1. Pearson DC, May GR, Fick GH, Sutherland LR. Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis. Ann Intern Med. 1995;123:132-42.

2. Feagan BG, Rochon J, Fedorak RN, Irvine EJ, et al., for the North American Crohn's Study Group Investigators. Methotrexate for the treatment of Crohn's disease. N Engl J Med. 1995;332:292-7.

3. Modigliani R. Immunosuppressors for inflammatory bowel disease: how long is long enough? Inflamm Bowel Dis. 2000;6:251-7.

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.