Safety, Efficacy, and Pharmacokinetics of Balsalazide in Pediatric Patients With Mild‐to‐Moderate Active Ulcerative Colitis: Results of a Randomized, Double‐blind Study

Abstract

Objectives A multicenter, double-blind study was conducted to evaluate the safety, efficacy and pharmacokinetics of balsalazide in pediatric patients with mild-to-moderate UC. Methods Sixty-eight patients, 5 to 17 years of age, with mild-to-moderate active UC based on the modified Sutherland UC activity index (MUCAI), were randomized to receive oral balsalazide 2.25 or 6.75 g/day for 8 weeks. The primary endpoint was clinical improvement (reduction of the MUCAI score by ≥3 points from baseline). Clinical remission (MUCAI score of 0 or 1 for stool frequency) and histological improvement after 8 weeks were also assessed. Pharmacokinetic parameters for balsalazide, 5-aminosalicylic acid, and N-acetyl-5-aminosalicylic acid were determined at 2 weeks. Adverse events and laboratory changes were monitored throughout the study. Results Clinical improvement was achieved by 45% and 37% of patients and clinical remission by 12% and 9% of patients receiving 6.75 and 2.25 g/day, respectively. Improvement in histologic grade was achieved by 8 of 16 (50%) and 3 of 10 (30%) patients receiving 6.75 and 2.25 g/day, respectively. No significant differences were seen in efficacy. Pharmacokinetics in 12 patients were characterized by large inter-subject variability and low systemic exposure. Adverse events were similar between the treatment groups, the most common being headache and abdominal pain. No clinically significant changes were observed in laboratory values, including those indicative of hepatic or renal toxicity. Conclusions Balsalazide is well-tolerated and improves the signs and symptoms of mild-to-moderate active UC in pediatric patients 5 to 17 years of age.

Colitis and Crohn’s Foundation (India) consensus statements on use of 5-aminosalicylic acid in inflammatory bowel disease

“…A multicenter, double-blind study on 68 patients with mild-to-moderate active UC in the age range 5 to 17 years, reported an achievement of clinical improvement in 45% and 37% of patients who received 5-ASA agent (oral balsalazide) 6.75 and 2.25 g/day, respectively while clinical remission was seen in 12% and 9% of patients respectively. The study supported the tolerability and safety profile of 5-ASA and its role in clinical remission in pediatric UC patients [ 121 ]. In another multicenter, randomized, double-blind study, 39% pediatric mild to moderate UC patients clinically improved with olsalazine and were asymptomatic after 3 months, compared to 79% on sulfasalazine ( P = 0.006); however, side effects were slightly less frequent with olsalazine [ 122 ].…”

Inflammatory Bowel Disease in Children and Adolescents

“…39 Balsalazide, the only 5-ASA agent with an indication from the US Food and Drug Administration in children, induces a clinical response at 8 weeks in 45% of children with mildly to moderately active UC and remission in 12%. 40 A large observational study showed that 30% of children with UC will maintain remission with administration of 5-ASA drugs alone. 41 Although 5-ASA drugs are still commonly prescribed for CD, systematic reviews do not support their efficacy.…”

Alternate Endpoints and Clinical Outcome Assessments in Pediatric Ulcerative Colitis Registration Trials

“…The primary efficacy endpoint in the adult Colazal trials was reduction of rectal bleeding and improvement in at least one of the other assessed symptoms (stool frequency, patient functional assessment, abdominal pain, sigmoidoscopic grade, and physician's global assessment), which were measured by the Sutherland UC Activity Index. Compared with the Sutherland UC Activity Index, MUCAI does not have the components of abdominal pain and patient functional assessment (8). The primary efficacy endpoint of the pediatric Colazal trial was the proportion of patients with clinical improvement assessed by the MUCAI, which includes measurements of stool frequency, rectal bleeding, physician's global assessment, and endoscopy (8).…”