Low dose balsalazide (1.5 g twice daily) and mesalazine (0.5 g three times daily) maintained remission of ulcerative colitis but high dose balsalazide (3.0 g twice daily) was superior in preventing relapses

• Published in: Gut 2001-12, Vol.49 (6), p.783-789
• Main Authors: Kruis, W, Schreiber, S, Theuer, D, Brandes, J-W, Schütz, E, Howaldt, S, Krakamp, B, Hämling, J, Mönnikes, H, Koop, I, Stolte, M, Pallant, D, Ewald, U
• Format: Article
• Language: English
• Subjects: aminosalicylic acid; Aminosalicylic Acids - administration & dosage; Aminosalicylic Acids - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; balsalazide; Biological and medical sciences; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - pathology; Colitis, Ulcerative - urine; Colon; Colon - pathology; Digestive system; Double-Blind Method; Drug Administration Schedule; Drug dosages; Endoscopy; Family medical history; Female; Humans; Inflammatory bowel disease; Male; Medical sciences; Mesalamine - administration & dosage; Mesalamine - adverse effects; Mesalamine - urine; mesalazine; Pharmacology. Drug treatments; Phenylhydrazines; Prodrugs - administration & dosage; Prodrugs - adverse effects; Studies; ulcerative colitis; Urine
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.49.6.783

BACKGROUND Balsalazide is a new 5-aminosalicylic acid (5-ASA) containing prodrug. Its efficacy in comparison with standard mesalazine therapy and the optimum dose for maintaining remission of ulcerative colitis are still unclear. AIMS To compare the relapse preventing effect and safety profile of two doses of balsalazide and a standard dose of Eudragit coated mesalazine. METHODS A total of 133 patients with ulcerative colitis in remission were recruited to participate in a double blind, multicentre, randomised trial: 49 patients received balsalazide 1.5 g twice daily, 40 received balsalazide 3.0 g twice daily, and 44 received mesalazine 0.5 g three times daily. Efficacy assessments were clinical activity index (CAI) and endoscopic score according to Rachmilewitz, and a histological score. In addition, laboratory tests were performed and urinary excretion of 5-ASA and its metaboliteN-Ac-5-ASA was analysed. The study lasted for 26 weeks. RESULTS Balsalazide 3.0 g twice daily resulted in a significantly higher clinical remission rate (77.5%) than balsalazide 1.5 g twice daily (43.8%) and mesalazine 0.5 g three times daily (56.8%) (p=0.006). The respective times to relapse were 161 days, 131 days (p=0.003), and 144 days (NS). Accordingly, pairwise contrasts of the final endoscopic score demonstrated a significant difference (p=0.005) between the two balsalazide treatment groups while differences between either of these two groups and mesalazine were not statistically significant. Patients treated with balsalazide excreted less 5-ASA andN-Ac-5-ASA than patients receiving mesalazine but these differences were not statistically significant. Discontinuation of the trial because of adverse effects occurred in nine patients: three in the balsalazide 1.5 g twice daily group, two in the balsalazide 3.0 g twice daily group, and four in the mesalazine 0.5 g three times daily group. No clinically important new drug safety related findings were identified in this study. CONCLUSIONS High dose balsalazide (3.0 g twice daily) was superior in maintaining remission in patients with ulcerative colitis compared with a low dose (1.5 g twice daily) or a standard dose of mesalazine (0.5 g three times daily). All three treatments were safe and well tolerated.