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Therapeutics

Low-dose maintenance mesalazine decreased relapse rate in cryptogenic proctitis

ACP J Club. 1998 Sep-Oct;129:43. doi:10.7326/ACPJC-1998-129-2-043


Source Citation

Marteau P, Crand J, Foucault M, Rambaud JC. Use of mesalazine slow release suppositories 1 g three times per week to maintain remission of ulcerative proctitis: a randomised double blind placebo controlled multicentre study. Gut. 1998 Feb;42:195-9.


Abstract

Questions

Can a low maintenance dose of slow-release, topical mesalazine prevent relapse of cryptogenic ulcerative proctitis? In patients who have had relapse, how effective is an increased dose of mesalazine for achieving remission?

Design

Randomized, double-blind, placebo-controlled trial with 1-year follow-up.

Setting

22 clinical centers in France.

Patients

95 patients (mean age 41 y, 54% women) who were ≥ 18 years of age, had cryptogenic proctitis and lesions limited to the rectum, had had ≥ 2 episodes of acute proctitis in the previous year, had been in clinical remission for < 2 weeks (i.e., no rectal bleeding, mucus in the stools, diarrhea, pain, or tenesmus), and had an endoscopy score of 0 or 1. Exclusion criteria included other maintenance treatments for ulcerative colitis and proctitis not caused by ulcerative colitis. Patients (n = 51) for whom oral salicylates were previously prescribed were included if their dose did not change during the study. Follow-up was 84%.

Intervention

Patients were allocated to mesalazine suppositories, 1 g 3 times/wk (n = 48), or a matching placebo (n = 47). If relapse occurred, the mesalazine dose was increased to 1 g/d.

Main outcome measures

Time to proctitis relapse. Secondary outcome measures included the number of patients with relapse and the remission rate in patients who had relapse.

Main results

Analysis was by intention to treat. A trend was shown toward greater mean relapse-free survival in patients allocated to mesalazine than in those allocated to placebo at 1 year (239 vs 166 d, P = 0.07). At 9 months, fewer patients allocated to mesalazine than to placebo had relapse (P = 0.03), but the difference was not statistically significant at 1 year (P = 0.18) (Table). Of patients who had relapse, those allocated to mesalazine were more likely than those allocated to placebo to achieve remission within 30 days (61% vs 28%, P = 0.001). No difference in adverse events existed between groups (P = 0.72).

Conclusions

In patients with cryptogenic proctitis, more patients in the mesalazine group than in the placebo group achieved remission at 9 months, but the difference was not statistically significant at 1 year. After relapse, an increased dose of mesalazine led to a higher rate of remission in patients allocated to mesalazine than in those allocated to placebo.

Source of funding: Ferring SA France.

For correspondence: Dr. P. Marteau, Service d'Hépato-Gastroentérologie, Hôpital Saint-Lazare, 75745 Paris Cedex 10, France. FAX 331-48-005622.


Table. Mesalazine vs placebo for cryptogenic proctitis*

Outcomes Mesalazine Placebo RRR (95% CI) NNT (CI)
Relapse at 9 mo 38% 60% 37% (4 to 60) 5 (3 to 51)
Relapse at 1 y 48% 62% 22% (-12 to 47) Not significant

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


Commentary

Ulcerative colitis affects approximately 250 000 persons in the United States alone and is responsible for the loss of > 1 million work days per year (1). The clinical course of ulcerative colitis is marked by exacerbations and remissions. The first line of therapy for mild to moderately active ulcerative colitis is aminosalicylates. Daily topical aminosalicylates have been shown to be effective in the treatment of proctitis and the maintenance of remission.

In the study by Marteau and colleagues, Pentasa (mesalazine) suppositories, 1 g given 3 times/wk, maintained remission for up to 9 months. For patients who had relapse, an increase in dose to 1 g/d increased the likelihood of remission so that, overall, more patients receiving mesalazine were in remission at 1 year (61% vs 28%, P < 0.001). This suggests that a subset of patients may benefit from daily rather than intermittent maintenance therapy and that patients maintained on intermittent mesalazine suppositories respond faster to daily therapy during an exacerbation.

In the United States, the only available topical aminosalicylate is a Rowasa (mesalamine) suppository, 500 mg, which is given twice daily and has a different delivery system from Pentasa.

The goal of medical therapy in ulcerative colitis is to use the lowest effective dose and dose interval. Although topical therapy is not for everyone, it has a quicker response time, decreased systemic side effects, and a less frequent dosing schedule than oral aminosalicylates. Topical therapy may be used as monotherapy for proctitis or in combination with oral medications for proctitis or more extensive disease. Topical aminosalicylates may maintain remission in patients with proctitis when given intermittently and are an important option for inducing and maintaining remission in patients with ulcerative colitis.

John R. Saltzman, MD
University of Massachusetts Medical CenterWorcester, Massachusetts, USA


Reference

1. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults. Am J Gastroenterol. 1997;92:204-11.