A Pilot Study of the Efficacy and Tolerability of AST-120 in the Treatment of Active Pouchitis

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Purpose: Bacterial toxins and increased production of deconjugated bile acids are speculated to play a role in the pathogenesis of pouchitis. While the majority of patients with pouchitis respond to antibiotics, relapse is common and non-absorbable and non-antibiotic-based agents are desirable to reduce bacterial resistance and systemic adverse effects associated with long-term antibiotic use. AST-120 is comprised of highly adsorptive, porous, carbon microspheres with the ability to adsorb small molecular weight toxins, inflammatory mediators, and harmful bile acids. The aim of this pilot study was to evaluate efficacy and tolerability of AST in the treatment of active pouchitis. Methods: Inclusion criteria: 1) active pouchitis patients with underlying ulcerative colitis (UC) with Pouchitis Disease Activity Index (PDAI) scores ≥ 7; and 2) discontinuation of antibiotic therapy for at least 2 weeks. Exclusion criteria included Crohn's disease of the pouch, and isolated cuffitis. In this open-label study, all eligible patients received AST-120 in 2 g sachets PO tid for 4 weeks. The efficacy endpoints were remission (PDAI score < 7) and clinical response (reduction of PDAI score of ≥ 3). Cleveland Global Quality of Life (QOL) and Short Inflammatory Bowel Disease Questionnaire were also assessed before and after the trial. Results: Ten patients were enrolled the trial: 9 completed the trial (mean age = 50 ± 10 yrs, SD; mean duration of UC = 16 ± 9 yrs; mean duration of ileal pouch = 7 ± 5 yrs) and one dropped out of the trial due to a viral upper respiratory infection 2 days after entry. Of the 9 patients, 4 (44%) had clinical remission and 5 (56%) achieved clinical response and (AST-120 effect on components of the PDAI illustrated below). There was numerical, but not statistically significant improvement in QOL scores. The agent was well tolerated; one patient had transient mild elevation of alkaline phosphatase. Conclusion: AST-120 appears to be effective and well tolerated in treating patients with active pouchitis. A randomized, placebo-controlled trial is warranted to assess long-term efficacy and safety of AST-120 in this indication.[figure1]Figure