Endoscopic Healing in Induction and Maintenance with Ustekinumab in the Phase 3 UNITI Crohnʼs Disease Program: 2016 ACG Presidential Poster Award

Abstract

Introduction: To evaluate endoscopic healing in the ustekinumab(UST) induction (UNITI-1&2)& maintenance (IM-UNITI) Phase 3 studies. Methods: Substudy patients (pts) had colonoscopies at baseline (˜UNITI Wk0), then 8 & 52 weeks later (IM-UNITI Wk44). A single central reader blindly scored all video endoscopies for ulcerations & simplifi ed endoscopic activity score for CD (SES-CD). At induction Wk0, pts received a single IV dose (UST 130mg, UST ˜6mg/kg, or PBO). At maintenance Wk0 (i.e. induction Wk8), pts with clinical response [CR] (CDAI decrease ≥100) to IV UST induction were re-randomized to subcutaneous (SC) PBO or UST 90mg (q12w or q8w) [Primary randomized maintenance population]. For the non-randomized maintenance groups: (1)UST induction non-responders received SC UST 90mg, then continued SC UST 90mg q8w if in CR 8wks later; (2)PBO induction nonresponders received UST IV 130mg, then continued SC UST 90mg q12w if in CR after 8wks; (3)PBO induction responders received PBO throughout. Pts with SES-CD ≥3 (i.e. ulceration in ≥1 segment) at induction Wk0 were eligible for analysis. Primary endpoint was change in SES-CD at induction Wk8 (Integrated UST group [induction studies & doses combined] vs PBO). Efficacy at maintenance Wk44 was evaluated in the primary randomized maintenance population & the post-hoc pooled maintenance population (randomized & nonrandomized populations combined).Table 1a: Induction Week 8 (UNITI-1&2)Table 1b: Maintenance Week 44 (IM-MUNITI)Results: UST induced significantly greater reduction in SES-CD at Wk8 vs PBO. Results were similar by induction study & UST dose. Other induction endoscopic endpoints also consistently favored UST vs PBO (Table 1a). In the primary randomized maintenance population at maintenance Wk44, trends for greater efficacy were seen with UST vs. PBO maintenance (especially UST 90mg q8w) but small sample sizes (UST n=46; PBO n=24) precluded definitive conclusions. In the larger post-hoc pooled maintenance population (Table 1b), consistent trends supporting UST maintenance, again especially UST 90mg q8w, were observed across endoscopic endpoints at Wk44. Conclusion: The endoscopy substudy primary endpoint was met; one IV UST dose induced significantly greater reduction in endoscopic disease activity vs PBO, even at a relatively early Wk8 evaluation. Greater proportions of pts receiving UST maintenance, especially UST 90mg q8w, achieved maintenance endoscopic endpoints vs PBO. Together, these data support efficacy of UST in inducing & maintaining endoscopic healing of the mucosa in CD.