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


Therapeutics

Oral mesalamine for ulcerative colitis

ACP J Club. 1992 Jan-Feb;116:13. doi:10.7326/ACPJC-1992-116-1-013


Source Citation

Sninsky CA, Cort DH, Shanahan F, et al. Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis. A multicenter study. Ann Intern Med. 1991 Sep 1;115:350-5.


Abstract

Objective

To evaluate the efficacy and safety of 2 dosage levels of oral mesalamine for treating mild-to-moderate ulcerative colitis.

Design

Randomized, double-blind, placebo-controlled, multicenter trial, stratified by center.

Setting

5 university medical centers, 3 private practices, and 1 inflammatory bowel disease center.

Patients

Patients between 18 and 75 years of age with mildly to moderately active ulcerative colitis confirmed by colonoscopy or proctosigmoidoscopy and barium enema within the previous 24 months were included. Patients with renal or hepatic dysfunction, allergy to aspirin or salicylate compounds, or who had used steroids < 1 month before study entry were excluded.

Intervention

Patients were randomly allocated to receive oral mesalamine (Asacol), either 1.6 g/d (n = 53) or 2.4 g/d (n = 53), or placebo (n = 52). Sulfasalazine was discontinued 1 week before entry. Potential contaminating or confounding drugs (e.g., steroids, aspirin) were not allowed during the trial.

Main outcome measures

Clinical status was assessed at study entry and after 3 and 6 weeks using a 4-point scale including these subscales: physician's global assessment, stool frequency, rectal bleeding, sigmoidoscopic findings, and patient's functional assessment. Patients were classified by their score as “in remission,” or in “improved,” “maintained,” or “worsened” condition.

Main results

131 of 158 randomized patients were included in the efficacy analysis, including 15 placebo; 3 mesalamine, 1.6 g/d; and 4 mesalamine, 2.4 g/d, patients who experienced treatment failure by 6 weeks. At 3 weeks the conditions of 74% of patients receiving the mesalamine, 2.4 g/d, had maintained, improved, or were in remission, compared with 48% of placebo patients (P = 0.003). At 6 weeks the conditions of 81% of the 2.4 g/d group and 68% of the 1.6 g/d group were not worsened compared with 50% of the placebo group (P = 0.003 and P = 0.03, respectively). In an intention-to-treat analysis, which included all 158 entry patients and considered the conditions of patients removed from the study to be worsened, the outcome of the 2.4 g/d group at 6 weeks was superior to placebo (P = 0.004) whereas the 1.6 g/d group did not differ from placebo (P = 0.2).

Conclusion

Oral mesalamine, 2.4 g/d, is effective in maintaining or improving mildly to moderately active ulcerative colitis compared with placebo at 6 weeks follow-up.

Source of funding: Norwich Eaton Pharmaceuticals, Inc.

Address for article reprint: Dr. C.A. Sninsky, Veterans Affairs Medical Center, Gastroenterology Section (111C), Gainesville, FL 32608-1197.


Commentary

Sulfasalazine is an effective treatment for ulcerative colitis, but up to one third of patients will develop side effects, some of them life threatening. Sulfasalazine is a combination of locally active 5-ASA with sulfapyridine as a carrier. Sulfapyridine has no apparent therapeutic effect, but it is responsible for the majority of adverse reactions. Attempts at drug desensitization to overcome side effects are sometimes unsuccessful and are contraindicated in patients who have serious hematologic disturbances (1).

To limit toxicity, formulations containing 5-ASA (mesalamine) without sulfapyridine have been developed. Oral mesalamine in a pH-sensitive polymer coating (Asacol) is one example. The coating delays the release of mesalamine until the drug reaches the colon.

In this well-designed study, Sninsky and colleagues have shown that oral mesalamine in a dose of 2.4 g/d is effective therapy for mildly to moderately active ulcerative colitis. Importantly, adverse reactions to the drug were rare and mild. Serious side effects required that the drug be withdrawn in only 2 of 51 patients.

Sulfasalazine remains a first-line drug for the treatment of ulcerative colitis. It is well tolerated by most patients and is inexpensive. For patients unable to take this medication, oral mesalamine is an excellent alternative. Patients who develop serious adverse reactions such as hemolytic anemia, agraagracytosis, dermatitis, headaches, or male infertility while taking sulfasalazine will likely tolerate mesalamine. Bloody diarrhea is an unusual complication of sulfasalazine treatment and can recur when mesalamine preparations are given as noted in this and other studies (2).

Drew K. Siegel, MD
U.S. Naval Hospital San Diego, California