Balsalazide for treatment of mild to moderate ulcerative colitis
Combined research at the Vanderbilt University School of Medicine, Nashville Medical Research Institute and Salix Pharmaceuticals has confirmed that treatment with balsalazide leads to earlier symptomatic relief than mesalamine, in patients with mild-to-moderate ulcerative colitis. These findings published in the American Journal of Gastroenterology 2002, are consistent with previous clinical trials comparing the two drugs. However, this is the first study to consider the effect of disease duration on the outcome, which was considered a potentially confounding factor in previous studies. In addition, the study proved balsalazide was a safe and well-tolerated treatment for ulcerative colitis, highlighting it as a promising treatment for the future.
The study was based on an 8 week, double-blinded trial of two different 5-aminosalicylic acid (5-ASA) drug formulations in patients with image confirmed ulcerative colitis. Mesalamine is composed of 5-ASA itself, whilst balsalazide is a newer preparation combining this active moiety with 4-aminobenzoyl-B-alanine by azo bonds. Bacteria in the colon break down balsalazide to release 5-ASA. Numerous clinical trials had already suggested balsalazide to be superior to mesalamine in controlling symptoms of ulcerative colitis. The present study thus aimed to further compare rates of symptomatic remission and to stratify patients based on disease duration and extent to understand the effect of these factors on the clinical response from the drugs. A total of 173 otherwise healthy patients, with mild-to-moderate ulcerative colitis were included in the study. They ranged form ages 12-80 and had greater than 12 cm of disease on sigmoidoscope, which was considered the cut-off value for the study. Patients were divided into four strata based on the time since diagnosis and the extent of disease. Patients were then randomly assigned to receive balsalazide 6.75g/day or mesalamine, pH-dependent delayed release tablets, 2.4g/day. Follow up was done at days 14, 28 and 56 with regard to symptoms and sigmoidoscope appearance of disease. Randomisation ensured there were no significant differences between study groups at baseline. At the end of the 8 week period both drug groups had similar rates of symptomatic remission. Those with newly diagnosed disease showed more favourable responses than those with a recent relapse of disease. However, at end point there were no statistically significant differences between responses from either drug across all strata. Researchers thus focused on the time taken for symptomatic remission. Researchers found that “within the strata, patients treated with balsalazide tended to achieve complete remission earlier than did patients treated with mesalamine.” Researchers also considered other efficacy parameters such as improvements in sigmoidoscopic, stool frequency, rectal bleeding and physician’s global assessment score which were significantly more improved in balsalazide patients earlier in the study. The research team was justified in concluding that balsalazide is as effective in the treatment of ulcerative colitis as mesalamine. Furthermore, researchers noted that “balsalazide was superior to mesalamine in the time to symptomatic remission.” In particular, study participants with newly diagnosed disease of only moderate extent, appeared to gain symptomatic relief much earlier with balsalazide compared to mesalamine. They postulated the favourable outcomes of balsalazide may be due to the reliability and efficiency of the delivery of the drug to the colon, the only site where the azo bonds can be reduced. Balsalazide should therefore be the preferred treatment for acute ulcerative colitis. However, as this study excluded patients with severe disease and multiple previous relapses, additional research is required to investigate mechanisms of action of the 5-ASA agents and possible modes of resistance in those with more advanced disease. (Source: Pruitt, R. et al, ‘Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of acute mild-moderate ulcerative colitis,’ The American Journal of Gastroenterology. Elsevier Science Inc., 2002, vol. 97, no.12.)