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


Therapeutics

Olsalazine was more effective than mesalazine in maintaining remission from ulcerative colitis

ACP J Club. 1992 Nov-Dec;117:68. doi:10.7326/ACPJC-1992-117-3-068


Source Citation

Courtney MG, Nunes DP, Bergin CF, et al. Randomised comparison of olsalazine and mesalazine in prevention of relapses in ulcerative colitis. Lancet. 1992 May 23;339:1279-81.


Abstract

Objective

To compare the efficacy and safety of olsalazine and mesalazine in maintaining remission of ulcerative colitis.

Design

Randomized, observer-blind, controlled trial of 12 months duration.

Setting

Gastroenterology outpatient department in a teaching hospital in Ireland.

Patients

100 eligible patients (age range 16 to 75 y, ulcerative colitis in remission at study entry, originally diagnosed by clinical, endoscopic, histologic, and radiologic criteria) were recruited consecutively. 30% to 32% of patients had proctitis; 44%, left-sided colitis; and 24% to 26%, pancolitis. Remission was defined as absence of symptoms or the presence of mild stable symptoms. Exclusion criteria were prescription of systemic steroids, azathioprine, or metronidazole within the previous month; pregnancy; and serious cardiac, pulmonary, hepatic, or renal disease. Intention-to-treat and per-protocol analyses included 99 and 82 patients, respectively.

Intervention

Patients were assigned to olsalazine (Dipentum), 1.0 g/d, or mesalazine (Asacol), 1.2 g/d, to be taken with meals (n = 50 in each group).

Main outcome measures

Treatment failure and patient satisfaction with treatment. Patients were examined and compliance checked every 3 months. A colonoscopy and mucosal biopsy were done at baseline and after 1 year. Relapse of colitis was defined as the development of severe new symptoms that warranted systemic steroid therapy.

Main results

Fewer patients assigned to olsalazine relapsed compared with those in the mesalazine group (12 patients [24%] vs 23 patients [46%], P = 0.025). {This absolute risk reduction (ARR) of 22% means that 5 patients would need to be treated (NNT) with olsalazine (compared with mesalazine) to prevent 1 addtional relapse, 95% CI 3 to 37; the relative risk reduction (RRR) was 47%, CI 7% to 70%.}* Similar findings were noted in the per-protocol analysis: 5 of 42 patients taking olsalazine (12%) relapsed compared with 13 of 40 patients (33%) taking mesalazine (P < 0.05): {ARR 21%; NNT 5, CI 5 to 36; RRR 63%, CI 11% to 85%}.* Men and women did not differ in relapse rate. More patients with proctitis or left-sided colitis relapsed compared with pancolitis (32%, 42%, and 18%, respectively). 19 patients assigned to olsalazine (38%) rated their condition as better and 10 patients (20%) as worse compared with 4 patients (8%) and 25 patients (50%), respectively, in the mesalazine group (P < 0.001). Both drugs were well tolerated with no differences in adverse reactions.

Conclusions

Olsalazine was more effective than mesalazine in maintaining remission from ulcerative colitis. Adverse effects of either drug were few.

Source of funding: No external funding.

For article reprint: Dr. M.G. Courtney, Professorial Unit (RCSI), Beaumont Hospital, Dublin 9, Ireland.

*Numbers calculated from data in article.


Commentary

Review: Most current drugs improve Crohn disease but do not prevent relapse

The 2 studies address many of the questions raised by clinical trials in inflammatory bowel disease. The article by Courtney and colleagues describes a large single-center comparative study of 2 newer aminosalicylates for the maintenance of remission in ulcerative colitis. The methods are similar to those used in previous trials comparing ASA derivatives with sulfasalazine, which found comparable efficacy but improved tolerability of the ASA derivatives compared with the standard (sulfasalazine) treatment. The results show that the azo-linked olsalazine compound, which delivers 5-ASA to the colon in a manner similar to sulfasalazine, is superior to the acrylic-coated preparation, mesalazine (Asacol).

Interpretation of the results should, however, take several factors into account. To optimize compliance (which was checked) the patients knew which drug they were taking; therefore previous experience with one or both of the medications at entry to the trial may have influenced their responses to treatment. Moreover, although the investigators were blinded to treatment, their definition of "remission" and "relapse" makes it difficult to completely exclude a systematic bias. It would also be helpful for clinicians to know whether different doses of the 2 drugs would have achieved similar results. In this study the drugs were administered at the manufacturers' recommended dosage; olsalazine was administered as 4 tablets, 250 mg each, and mesalazine as 3 tablets, 400 mg each. Although the compliance of the 2 groups of patients was comparable, the differences in results could be explained by a lack of comparability between the mesalazine and olsalazine delivery systems. The effectiveness might have been similar if higher doses of mesalazine (e.g., 4 tablets, 1.6 g) had been used.

Salomon and colleagues used the technique of meta-analysis to determine the overall efficacy of drugs currently used for the treatment of Crohn disease. The authors emphasize that different end points and patient populations were included that may obscure effectiveness or lack thereof in subgroups of patients with Crohn disease. Nevertheless, there is a consistency in clinical trials showing a relatively modest benefit for our current therapies, which include sulfasalazine, 5-ASA, steroids, and immunosuppressives. The "therapeutic advantage" in inducing complete clinical remission, which ranged from 10% for azathioprine and 11% for sulfasalazine to 29% for steroids in active Crohn disease, emphasizes the need to continue exploring new therapeutic approaches. The meta-analysis includes only trials that used single agents, whereas clinicians recognize the frequent empiric need for combination approaches. Future studies will need both to assess single and combination therapies in predefined subsets of patients with Crohn disease and to have well-defined clinical end points.

The 2 studies emphasize that we can no longer lump all patients with ulcerative colitis or Crohn disease together, treat them with a single drug at a single dose, and expect to identify substantial differences that make clinical practice straightforward. Until larger trials incorporating predefined subpopulations of patients treated with varying doses or combinations are done, we will have to depend on results from limited controlled trials combined with clinical experience to form individualized approaches to patients. Although this has been the basis for our therapeutic decisions, we hope and anticipate that clinical research in inflammatory bowel disease will continue to advance as our ability to distinguish clinically important differences in patients improves.

Stephen B. Hanauer, MD
University of Chicago Medical CenterChicago, Illinois, USA