Efficacy and Safety of a Tacrolimus Lipid Suspension Enema in Mild-to-Moderate Ulcerative Colitis: A Multicenter, Prospective, Double-Blind, Phase II Randomized Controlled Trial.

PURPOSE: A novel tacrolimus lipid suspension (TLS) enema was developed for the management of mild-to-moderate mesalamine-refractory ulcerative colitis (UC). The aim of this study was to evaluate the efficacy and safety of tacrolimus lipid suspension enema 2 mg (TLS-2) and 4 mg (TLS-4) in this patient population.

METHODS

In this multicenter, double-blind, Phase II trial, adult patients with mild-to-moderate mesalamine-refractory UC were randomized (1:1) to receive TLS-2 or TLS-4 for 4 weeks. Primary end points were change in the modified UC Disease Activity Index, remission rates, and time to resolution of rectal bleeding. Secondary end points included relapse rates, Short Inflammatory Bowel Disease Questionnaire scores up to 4 weeks after treatment, and clinical safety.

FINDINGS: A total of 60 patients were randomized to receive TLS-2 or TLS-4. Both groups exhibited significant reductions in the modified UC Disease Activity Index after 4 weeks (P < 0.001), with remission in >50% of patients. The median time to resolution of rectal bleeding was <14 days. Relapse occurred in 6% to 10% of patients within 4 weeks after treatment. Short Inflammatory Bowel Disease Questionnaire scores significantly improved in both arms, and no major safety issues were reported.

IMPLICATIONS: Tacrolimus lipid suspension enema at both 2 and 4 mg doses was effective and well-tolerated. Both formulations also substantially improved patient-reported outcomes.

CLINICAL TRIAL REGISTRY OF INDIA IDENTIFIER: CTRI/2015/10/006252.