Tu1861 A RANDOMIZED, OBSERVER-BLINDED PHASE IB MULTIPLE, ASCENDING DOSE STUDY OF UTTR1147A, AN IL-22FC FUSION PROTEIN, IN HEALTHY VOLUNTEERS AND ULCERATIVE COLITIS PATIENTS.

BACKGROUND: Ustekinumab (UST) is an effective therapy for moderate-severe ulcerative colitis (UC). 1,2 Histologic and endoscopic improvement of mucosa after induction are associated with clinical remission and steroid-free clinical remission at maintenance Wk44. 3 The association of histologic-endoscopic mucosal healing after UST induction or maintenance therapy with 2-yr outcomes in moderate-severe UC is not known.METHODS: In the UNIFI study of UST in moderate-severe UC, histologic-endoscopic mucosal healing was defined as achieving both endoscopic improvement (Mayo endoscopy subscore £1) and histologic improvement (ie, neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue; based on Geboes score).Associations of mucosal improvement after induction (irrespective of treatment) or UST maintenance with long-term efficacy of UST, disease severity, inflammation level, and dose adjustment were evaluated up to Wk92 in the long-term extension(LTE) of UNIFI.Analysis was conducted in pts who were randomized to receive UST maintenance therapy and continued UST in LTE.Tests with p<0.05 were considered statistically significant.RESULTS: Pts with histologic-endoscopic mucosal healing after induction had significantly lower disease activity (partial Mayo score and stool frequency) and a trend for lower inflammation measured by CRP and fecal calprotectin at maintenance Wk44 than those without induction mucosal healing(Table1).These improvements in disease activity were retained through LTE Wk92, with pts with induction histologic-endoscopic mucosal healing showing a continuous reduction of disease activity.Significantly lower disease activity, CRP, and fecal calprotectin were also observed through LTE among pts with histologic-endoscopic mucosal healing after UST maintenance compared to those without(Table1).Pts with histologic-endoscopic mucosal healing after induction remained on treatment longer than those without(p<0.05).Pts with histologicendoscopic mucosal healing after induction or maintenance were less likely to receive dose adjustment during LTE, but this association was not statistically significant.CONCLUSION: Early macroscopic and microscopic improvement of the mucosa is an indicator of positive long-term clinical outcomes and reductions in inflammatory burden. 1 BE Sands, et al.Safety and Efficacy of Ustekinumab Induction Therapy in Patients with Moderate to Severe Ulcerative Colitis: Results from the Ph 3 UNIFI Study.