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


Therapeutics

Oral mesalamine was effective and safe in maintaining remission in ulcerative colitis

ACP J Club. 1996 May-June;124:67. doi:10.7326/ACPJC-1996-124-3-067


Source Citation

The Mesalamine Study Group. An oral preparation of mesalamine as long-term maintenance therapy for ulcerative colitis. A randomized, placebo-controlled trial. Ann Intern Med. 1996 Jan 15;124:204-11.


Abstract

Objective

To evaluate the effectiveness and safety of mesalamine in maintaining remission in patients with quiescent ulcerative colitis.

Design

Randomized, double-blind, placebo-controlled trial with 6-month treatment duration.

Setting

8 private practices, 5 university-based medical centers, and 4 hospitals or clinics in the United States.

Patients

264 patients (mean age 42 y, 55% men) with documented ulcerative colitis who had been in remission for ≥ 1 month while receiving stable doses of sulfasalazine or any oral mesalamine product. Exclusion criteria were pregnancy, lactation, history of allergy or intolerance to aspirin or salicylates, history of extensive bowel resection causing the short-bowel syndrome, or laboratory evidence of renal or hepatic dysfunction.

Intervention

90 patients were allocated to 0.8 g/d of coated mesalamine, 87 patients were allocated to 1.6 g/d of coated mesalamine, and 87 patients were allocated to placebo.

Main Outcome Measures

Maintenance of remission, time to relapse, adverse effects, and safety.

Main Results

In the intention-to-treat analysis, remission was maintained in 57 patients (63%) who received 0.8 g/d of mesalamine and in 61 patients (70%) who received 1.6 g/d of mesalamine compared with 42 patients (48%) who received placebo (P ≤ 0.05 for comparison between mesalamine groups and placebo). {This absolute risk improvement of 22% means that 5 patients would need to be treated with 1.6 g/d of mesalamine (rather than placebo) for 6 months to have 1 additional patient maintain remission, 95% CI 3 to 14; the relative risk improvement was 45%, CI 13% to 90%.}* Time to relapse was longer in patients who received 1.6 g/d of mesalamine compared with placebo (P = 0.008). The number of adverse effects was similar among the 3 treatment groups. The most frequently reported adverse effects were headache, flu syndrome, diarrhea, rhinitis, and abdominal pain. No clinically significant changes were seen in hematologic, hepatic, or renal laboratory profiles.

Conclusion

Oral coated mesalamine at dosages of 0.8 g/d and 1.6 g/d was safe and effective in maintaining remission in patients with ulcerative colitis.

Source of funding: In part, Procter & Gamble Pharmaceuticals.

For article reprint: Dr. S.B. Hanauer, Division of Gastroenterology, University of Chicago Hospital, 5841 South Maryland Avenue, Box 400, Chicago, IL 60637, USA. FAX 312-702-2182.

*Numbers calculated from data in article.


Commentary

The strong tendency of chronic idiopathic ulcerative colitis to relapse (1) is a challenge to physicians and a source of frustration to patients. The relapse rate of 52% in 6 months among placebo-treated patients in this study is in keeping with previously observed relapse rates (2). Sulfasalazine has been shown to be effective and generally well tolerated, but there are bothersome side effects and rare idiosyncratic reactions that seem to be related to the sulfapyridine portion of the molecule. The 5-aminosalicylic acid (5-ASA) moiety (mesalamine) has been shown to be the active portion.

Several 5-ASA preparations are now available on the market. Although there are important differences in how the manufacturing processes protect mesalamine from gastric acid destruction and small bowel absorption, the different preparations are probably equivalent in therapeutic effectiveness and more effective than placebo, as confirmed in this excellent study. Several studies are cited by the authors that show the equivalency of mesalamine and sulfasalazine in maintaining remission. Mesalamine, 1.6 g/d, is equivalent to 4 g/d of sulfasalazine. The cost per day (approximately U.S. $2.45) of brand-name mesalamine (4 tablets of 400 mg) does not differ from the daily costs of sulfasalazine (8 tablets of 500 mg). The daily cost of generic sulfasalazine (not available for mesalamine) is approximately U.S. $1.68. Although not objectively confirmed by prospective studies, a strong clinical impression exists that if suppressive therapy is discontined before the end of 5 years, a relapse will eventually occur in most patients.

James L. Achord, MD
University of Mississippi Medical CenterJackson, Mississippi, USA


References

1. Edwards EC, Truelove SC. The course and prognosis of ulcerative colitis. Gut. 1963;4:299-308.

2. Sinclair TS, Brunt PW, Mowat NA. Non-specific proctocolitis in northeastern Scotland: a community study. Gastroenterology. 1983;85:1-11.