Safety and efficacy of two dose formulations of alicaforsen enema compared with mesalazine enema for treatment of mild to moderate left-sided ulcerative colitis: a randomized, double-blind, active-controlled trial.

摘要

BACKGROUND: Alicaforsen is an antisense oligonucleotide inhibitor of intercellular adhesion molecule 1 protein expression with activity in subjects with ulcerative colitis and pouchitis. AIM: To compare the effects of alicaforsen enema to standard of care mesalazine (mesalamine) enema in subjects with mild to moderate active left-sided ulcerative colitis. METHOD: A randomized, double-blind, active-controlled multicentre clinical trial. Subjects received a nightly enema of 120 mg alicaforsen (n=55), 240 mg alicaforsen (n=50), or 4 g mesalazine (n=54) for 6 weeks, followed by a 24-week monitoring period. The primary end point was Disease Activity Index at week 6. Clinical improvement, remission and relapse were secondary end points. RESULTS: No significant difference was observed between treatment arms in the primary end point. However, the median duration of response to alicaforsen enema treatment was two- to threefold longer (128 and 146 days) in comparison with mesalazine (54 days). Complete mucosal healing occurred in 24% of the 240 mg alicaforsen group, when compared with 17% in the mesalazine. CONCLUSIONS: Alicaforsen enema demonstrated an acute response and safety profile similar to mesalazine enema, but was differentiated by a more durable response. The extended length of remission suggests that alicaforsen enema treatment may have a disease modifying effect.