Efficacy in biologic failure and nonbiologic-failure populations in a phase 3 Study of Ustekinumab in moderate-severe ulcerative colitis: UNIFI

Background: Ustekinumab (UST) was effective in Ph3 induction & maintenance of moderate-severe UC. Efficacy in biologic-failure (BF) and nonbiologic-failure (NBF) populations was evaluated. Methods: Pts were randomized to baseline IV induction UST (130 mg or 6 mg/kg) or PBO. Responders to IV UST induction entered maintenance and were randomized to SC UST90 mg (q12wks or q8wks) or PBO. Primary endpoint for wk8 induction and wk44 maintenance was clinical remission. Major secondary endpoints: wk8 induction = endoscopic healing, clinical response, & change from baseline in total IBDQ score; wk44 maintenance = maintenance of clinical response, endoscopic healing, corticosteroid-free clinical remission, & maintenance of clinical remission in baseline remitters. Results: Among documented BF patients (51.1% of randomized pts), 98.8% failed ≥1 anti-TNF, 32.6% failed both anti-TNF & vedolizumab. NBF pts were predominantly bio-naïve (94.3%). In induction, for BF&NBF pts, proportions of pts who achieved clinical remission was significantly greater for UST6 mg/kg and 130 mg vs. PBO. For BF&NBF pts, major secondary endpoints of clinical response, endoscopic healing & change from baseline in IBDQ were significantly greater for UST6 mg/kg and 130 mg vs. PBO (Table1). Though treatment differences were generally similar between BF&NBF pts, rates were consistently lower for BF pts in each treatment group. In maintenance, for BF&NBF pts, proportions of pts who achieved clinical remission was significantly greater for USTq8w and q12w vs. PBO; proportions of pts who achieved each major secondary endpoint were generally greater for USTq8wk and q12wk vs. PBO (Table2). (Table Presented) Conclusion: UST was effective for induction & maintenance treatment of moderate-severe UC pts with history of biologic failure (ie, TNFantagonists and/or vedolizumab) as well as pts without history of biologic failure.