Early improvement after intravenous ustekinumab induction in patients with ulcerative colitis: Results from the UNIFI induction trial

INTRODUCTION:

The UNIFI induction study evaluated the efficacy and safety of ustekinumab (UST) in patients with moderately to severely active ulcerative colitis (UC) after a single intravenous infusion. In this analysis, we evaluated the rapidity of the onset of the treatment effect.

METHODS:

Eligible patients were randomly assigned to placebo (PBO) or UST 130 mg or ;6 mg/ kg. Patients recorded stool frequency and categorized rectal bleeding daily for the 7 days before each visit. Partial Mayo scores were calculated at baseline and Week 2 using the average of the stool frequency and rectal bleeding scores from the most recent consecutive 3-day period before the visit and the physician's global assessment score recorded at the visit. C-reactive protein (CRP) and fecal biomarkers were measured at baseline and Day 14.

RESULTS:

At baseline, the mean 3-day average daily stool frequency was 7.0 in the PBO group, 6.9 in the UST 130-mg group, and 7.0 in the UST ;6-mg/kg group. Patients receiving UST showed greater reductions in the daily number of stools compared with PBO as soon as the first assessment time point at Day 7. Mean changes from baseline in daily stool frequency were -0.7 for PBO, -1.0 for UST 130-mg (P = 0.098), and -1.2 for UST ;6-mg/kg group (P = 0.018) by Day 7, respectively, and -0.9, -1.6 (P < 0.001), and -1.9 (P < 0.001) by Day 13, respectively (Figure 1). Rectal bleeding scores at baseline and Week 2 are summarized in Figure 2. Patients receiving UST showed significantly greater improvement from baseline to Day 14 in partial Mayo score and CRP (Table, P < 0.001 for all comparisons of UST vs PBO). Differences between the UST and PBO treatment groups in mean changes from baseline to Day 14 in fecal calprotectin did not reach significance (PBO -33.96 mg/kg, UST 130 mg 79.12 mg/kg [P = 0.875], UST ;6 mg/kg -412.68 mg/kg [P = 0.152]). However, patients receiving UST showed significantly greater improvement in fecal calprotectin at Week 4 (mean changes from baseline: PBO -226.78 mg/kg, UST 130 mg -881.22 mg/kg [P = 0.013], UST ;6 mg/kg -802.75 mg/kg [P < 0.001]). Similar results were observed for fecal lactoferrin.

CONCLUSION:

The effect of UST began rapidly after induction, with symptomatic improvement and reduction of systemic inflammation seen as early as the first assessments at Days 7 and 14, respectively. (Figure Presented).