EFFICACY IN BIOLOGIC-FAILURE AND NONBIOLOGIC-FAILURE POPULATIONS IN A PHASE 3 STUDY OF USTEKINUMAB IN MODERATE-SEVERE ULCERATIVE COLITIS: UNIFI

Background: Ustekinumab (UST), an IL12/23 blocker approved for Crohn's disease, was effective in Ph3 induction and maintenance of moderate-severe ulcerative colitis (UC). Efficacy in biologic-failure (BF) and nonbiologic-failure (NBF) populations was evaluated. Methods: Pts were randomized to a baseline intravenous (IV) induction UST dose (130mg or weight-range based doses approximating 6mg/kg (~6mg/kg)), or PBO. Responders to UST IV induction entered maintenance and were randomized to SC 90mg UST (q12wks or q8wks), or PBO. Primary endpoint for wk8 induction and wk44 maintenance was clinical remission. Major secondary endpoints for wk8 induction: endoscopic healing, clinical response, and change from baseline in total IBDQ score and wk44 maintenance: maintenance of clinical response, endoscopic healing, corticosteroid-free clinical remission, and maintenance of clinical remission in baseline remitters. Results: Among pts with documented BF (51.1% of randomized pts), 98.8 % had failed at least 1 anti-TNF, 32.6% had failed both anti-TNF and vedolizumab. NBF pts were predominantly bio-naïve (94.3%). In induction, for BF and NBF pts, proportions of pts who achieved clinical remission was significantly greater for UST ~6mg/kg and 130mg vs PBO (BF pts-P<0.001 for both doses; NBF pts-P<0.05 for both doses, respectively, Table 1). For BF and NBF pts, major secondary endpoints of clinical response and endoscopic healing and change from baseline in IBDQ were significantly greater for UST ~6mg/kg and 130mg vs PBO (Table 1). Though treatment differences were generally similar between BF and NBF pts, rates were consistently lower for BF pts in each treatment group. In maintenance, for BF and NBF pts, proportions of pts who achieved clinical remission was significantly greater for UST q8w and q12w vs PBO (BF pts- P<0.001, P=0.044, respectively; NBF pts- P=0.024, P=0.020, respectively, Table 2). For BF and NBF pts, proportions of pts who achieved each major secondary endpoint was generally greater for UST q8wk and q12wk vs PBO. In BF pts, the efficacy of UST q8wk was generally greater than UST q12wk (Table 2). Conclusion: UST was effective for induction and maintenance treatment of moderate-severe UC pts with a history of biologic therapy failure (ie TNF-antagonists and/or vedolizumab) as well as pts without a history of biologic therapy failure who were predominantly bio-naive. [Table Presented] [Table Presented]