Innovative drug for ulcerative colitis continues to show benefit in clinical trials

Research has once again confirmed the safety and efficacy of balsalazide, an aminosalicylate derivative, in the treatment of ulcerative colitis. A study published in a 2002 issue of the American Journal of Gastroenterology reinforces previous research that balsalazide produces more rapid and greater improvement in ulcerative colitis symptoms compared to mesalamine. Furthermore, this study closely examined the safety profile of balsalzide confirming it is just as safe as equimolar doses of mesalamine and that there is no significant increase in adverse effects with a higher dose of balsalazide.

Ulcerative colitis is an inflammatory disorder of the large intestine characterised by relapsing and remitting episodes of abdominal pain, urgency, and diarrhoea containing blood and mucus. It is most common in the 15-40 year old age group and causes significant morbidity for its sufferers. It is now well-recognised that aminosalicylic acid medications should be the primary treatment for ulcerative colitis. A study published in the American Journal of Gastroenterology in 2002 compared two such medications namely, mesalamine and balsalazide, in the treatment of mild-moderate ulcerative colitis. Mesalamine contains the active moiety 5-aminosalicylic acid (5-ASA) which is activated in the colon by a delayed-release mechanism triggered by a pH shift. This mechanism however can pose problematic as early and late release can lower the amount of 5-ASA available at the target site. In addition, early release of the 5-ASA in the small intestine can increase absorption and lead to nephrotoxicity and other side effects. An alternative release mechanism is used in balsalazide where 5-ASA is azo-bonded to 4-aminobenzoyl-B-alanine. This formulation ensures the active 5-ASA is only released at the target site in the colon under the action of azoreductase enzymes produced by colonic bacteria. The latter mechanism is a more reliable and reducible mechanism for delivery of the drugs to the colon. Therefore balsalzide is expected to produce a more rapid improvement of symptoms in ulcerative colitis. Several studies have confirmed the benefits of balsalazide over delayed-release formulations such as mesalamine, in terms of efficacy. However, some concerns exist regarding the safety and tolerability of other azo-bonded drugs such as olsalazine and sulfasalazine. The present study therefore aimed to assess the dose-response effects of balsalazide and compared the safety profile of high-dose balsalazide with that of mesalamine (2.4 g daily considered to be an eqimolar dose). Research was conducted at 15 centres within the United States and Puerto Rico, including a total of 154 patients with mild-to-moderate ulcerative colitis confirmed by flexible sigmoidoscopy. Patients were randomly assigned to one of three treatment groups; high-dose balsalazide (6.75g daily), low-dose balsalazide (2.25g daily) and the approved dose of mesalamine (2.4g daily). Patients were treated for an 8 week period and were followed up with sigmoidoscopy at 2, 4 and 8 weeks. Primary results showed that the greater dose of balsalazide produced a significantly greater improvement in symptoms of rectal bleeding and stool frequency, sigmoidoscopic grade (definitive diagnostic sign) and Physician’s Global Assessment. As expected, balsalazide also had a more rapid onset of action compared to mesalamine as well as greater improvements in the 8 week sigmoidoscopic scores and superiority in five of the seven efficacy parameters. These benefits are attributed to a greater proportion of the daily 5-ASA dose reaching the colon. Similar results have been observed in previous studies of the two drugs. Furthermore, balsalazide (6.75g daily) was well tolerated and safety evaluations showed that adverse events were no more frequent than with the approved dose of mesalamine and that it had a similar safety profile to low-dose balsalazide (2.25g daily). This study was well designed and controlled and thus provided firm evidence that high-dose balsalazide (6.75g daily) for 8 weeks is safe and effective for the treatment of mild-moderate ulcerative colitis. In conjunction with previous research, we can thus confirm that the new and innovative drug balsalazide is effective at maintaining remission long-term and is efficacious in the short-term treatment of active disease. These benefits are present without causing a dose-related increase in side-effects. It is therefore confirmed that balsalazide may be suitable to prescribe for patients with ulcerative colitis as part of routine clinical practice. Source: Levine D, Riff D, Pruitt R, Wruble L, Koval G, Sales D, Bell J & Johnson L. A Randomized, Double Blind, Dose-Response Comparison of Balsalazide (6.75 g), Balsalazide (2.25 g), and Mesalamine (2.4 g) in the Treatment of Active, Mild-to-Moderate Ulcerative Colitis, The American Journal of Gastroenterology 2002; 97 (6): 1398-1407.