Treatment of Ulcerative Colitis with 5-Aminosalicylic Acid

TO THE EDITOR:

Sutherland and colleagues [1] recently discussed the relative value of sulfasalazine and other 5-aminosalicylic acid preparations in the treatment of ulcerative colitis. There was an inconsistency in the authors' interpretation of the studies comparing 5-aminosalicylic acid with placebo. For the studies involving Dipentum (Kabi Pharmacia, Piscataway, New Jersey), Pentasa (Marion Merrell Dow, Kansas City, Missouri), and Rowasa (Solvay Pharmaceuticals, Marietta, Georgia), the response rates appear to be the percentages of patients who either improved or achieved remission. For the studies involving Asacol (Procter & Gamble Pharmaceuticals, Norwich, New York), however, the response rates quoted include only the percentages of patients who achieved remission. For our study (2; authors' reference 23), for example, the response rates for Asacol (2.4 g/d) and placebo are quoted as 11.3% and 3.8%, respectively. These values represent the rates for remission; the rates for improvement plus remission were 49% and 23%, respectively. Similarly, the response rates quoted for Schroeder and coworkers' study of Asacol (4.8 g/d) and placebo are the remission rates of 23.7% and 5.3%, respectively (3; authors' reference 33). The rates for improvement plus remission in the study by Schroeder and colleagues were 74% and 18%, respectively. Furthermore, many of the patients enrolled in our study were either refractory to or intolerant of sulfasalazine [4].

The authors correctly state that no uniform definition of a response existed across the studies. In contrast to other studies summarized by Sutherland and colleagues, ours used a composite scoring system that not only incorporated all the relevant parameters of interest but also did not allow a patient to be considered to have improved if deterioration was noted in any single parameter. We believe that our definition for improvement is the most stringent criterion of any scoring system cited by the authors.

The results of the meta-analysis of studies comparing 5-aminosalicylic acid with sulfasalazine indicate that these two treatments are equally effective. Differences in tolerability can, however, affect the outcome of treatment. We therefore agree with the authors' comment that because patients with known sulfasalazine intolerance were excluded, a clinically important difference may have been missed. With some formulations of 5-aminosalicylic acid, improved tolerability may permit the delivery of relatively high doses of the therapeutic agent to the colon without requiring dose titration. Nonetheless, given the cost of the newer preparations, clinicians should reserve their general use for patients who 1) are allergic to sulfa preparations, 2) experience a serious side effect requiring the cessation of sulfasalazine, 3) are men concerned about fertility, and 4) are refractory to tolerable doses of sulfasalazine.

We believe that certain physicians and patients are willing to settle for suboptimal disease control and side effects that could be readily addressed by these newer preparations. In other instances, some patients become accustomed to fatigue or other nonspecific side effects associated with sulfasalazine that are not noticed until a newer 5-aminosalicylic acid preparation is tried. Finally, it is our clinical experience that higher doses of Asacol (2.4 to 4.8 g/d) are well tolerated and provide an important therapeutic advantage in patients with refractory ulcerative colitis and possibly in those with Crohn colitis.

• Copyright 2004 by the American College of Physicians