Clinical trial: Association between early disease clearance and long-term outcomes - 4-year results from the Phase 3 UNIFI Study of Ustekinumab in Ulcerative Colitis

Background: Achievement of disease clearance (simultaneous symptomatic remission and histo-endoscopic mucosal improvement [HEMI]) following induction therapy may lead to better long-term outcomes in ulcerative colitis (UC). Aim: To evaluate disease clearance in the phase 3 UNIFI program and its association with long-term outcomes. Methods: UNIFI comprised randomised, placebo-controlled induction and maintenance studies and a long-term extension, which evaluated intravenous ustekinumab induction (130 mg or ~6 mg/kg) and subcutaneous ustekinumab maintenance therapy (90 mg every 8 or 12 weeks) through 4 years in patients with UC. Results: Disease clearance was achieved by 5.9%, 15.2% and 15.1% of patients 8 weeks after placebo or ustekinumab 130 mg or ~6 mg/kg induction, respectively. Among ustekinumab induction responders randomised to ustekinumab maintenance therapy who did or did not achieve disease clearance 8 weeks after induction, 63.6% and 35.2% (nominal p < 0.001), respectively, achieved clinical remission (Mayo score ≤ 2, no individual subscore > 1) at Week 44. Among ustekinumab induction responders randomised to ustekinumab maintenance therapy who achieved disease clearance, symptomatic remission without HEMI, or neither symptomatic remission nor HEMI 8 weeks after induction, 73.4%, 53.5% (nominal p = 0.002) and 45.1% (nominal p < 0.001), respectively, achieved symptomatic remission (Mayo stool frequency subscore 0/1, rectal bleeding subscore 0) and 58.2%, 46.5% (nominal p = 0.09) and 42.7% (nominal p = 0.05), respectively, achieved Inflammatory Bowel Disease Questionnaire remission (score ≥ 170) at Week 200. Conclusions: Patients who achieved disease clearance 8 weeks after ustekinumab induction were more likely to be in long-term clinical, symptomatic and quality of life remission with ustekinumab maintenance treatment than patients who did not. Trial Registration: NCT02407236.