390 Maintenance Treatment of Ulcerative Colitis with 5-Aminosalicylic Acid (5-ASA): Results from the Italian Population of a One Year, Randomized, Multinational Study Comparing MMx® with Asacol®

Abstract

Purpose: Basiliximab (BSX) is a chimeric monoclonal antibody that binds with high affinity to CD25, thereby inhibiting IL-2 binding, and IL-2 mediated proliferation of lymphocytes. Evidence suggests that IL-2 plays a role in the development of steroid-resistant T lymphocytes, and an open label study of BSX in steroid-resistant ulcerative colitis (UC) suggested benefits in reduced disease activity and steroid dose. We sought to determine the efficacy and safety of BSX in steroid-refractory UC. Methods: Adults with moderate to severe (Mayo score ≥6 and endoscopic subscore ≥2) UC extending above the rectum despite at least 14 days of oral prednisone (PRED) 40 to 50 mg/d prior to study entry. Concomitant 5ASA, 6MP/AZA were permitted with stable doses. Subjects with systemic features of toxicity, or who had received infliximab or cyclosporine within 3 months, or IV steroids or rectally administered medications within 2 weeks, were excluded. The first 135 subjects were randomized 1:1:1 to blinded BSX 40 mg, 20 mg, or placebo (PBO) IV at weeks 0, 2, 4. An additional 14 subjects were randomized to BSX 40 mg or placebo groups after the first 135 subjects were enrolled. All subjects received PRED 30 mg/d po from day 0 to week 2, then tapered by 5 mg weekly to 20 mg/d, and maintained this dose till week 8. The primary analysis was a comparison of the rate of clinical remission (Mayo score ≤2, no subscore >1) in the BSX 40 mg group compared to PBO at week 8. Secondary analyses compared BSX 20 mg to PBO at week 8, and clinical response (decrease in Mayo score by ≥3) for both groups to PBO at week 8 using Cochran-Mantel-Haenzel test stratified by Mayo Score (≤10, >10), use of 6MP/AZA, and geographic region of study site. Subjects were followed until week 12 for safety. The study had 80% power to detect a difference of 21% assuming PBO clinical remission rate of 19% with a 2-sided alpha of 0.1. Results: A total of 149 subjects were randomized and received at least 1 dose of study drug. Results are shown in the table below. Six subjects (2 in each group) had serious adverse events, including 1 patient assigned to BSX 20 mg who died with disseminated tuberculosis and previously undiagnosed HIV. Forty-five percent of subjects who received BSX developed neutralizing anti-BSX antibodies. Conclusions: Basiliximab was not effective for steroid sensitization and induction of remission in outpatients with steroid-resistant moderate-to-severe UC.