P034 EFFICACY OF USTEKINUMAB IN CROHN'S DISEASE AT MAINTENENCE WEEK 56: IM-UNITI STUDY. (7th February 2019) - Sandborn, William J
Abstract: Background: Ustekinumab (UST) is a human IgG1κ monoclonal antibody that binds to the p40 protein subunit, which is common to both IL-12 & IL-23 cytokines. It is approved for use in treatment of moderately to severely active Crohn's disease (CD). The primary endpoint data (Wk 44) from the pivotal Phase 3 study, IM-UNITI, has been previously reported. We examined efficacy of UST after 1 year of maintenance therapy (Wk 56). Methods: The Phase 3 development program of UST in CD included two multi-center, double-blind, placebo (PBO) controlled 8-week induction studies, UNITI 1 (anti-TNF therapy failures) and UNITI 2 (conventional therapy failures) comprising 1281 patients (pts). Pts in clinical response (reduction in Crohn's Disease Activity Index [CDAI] ≥100 points or in clinical remission) at Wk 8 to intravenous (IV) UST induction in UNITI 1 and UNITI 2 were randomized in IM-UNITI in a 1:1:1 ratio to receive subcutaneously (SC) administered UST 90mg q8w, 90mg q12w, or PBO. All pts completing treatment at Wk 44 of IM UNITI were qualified to participate in the IM-UNITI extension study. The study was unblinded when Wk 44 analyses were completed. Due to the durable biologic effect of a single IV induction, 36% of the randomized withdrawal population on SC PBO in maintenance were still in remission at Wk 44. At Wk 56, 84.6% of the pts remained blinded; unblinded pts were conservatively assumed to have same remission status as Wk 44. Wk 56 remission data were assessed in this post-hoc analysis of the primary randomized population of 388 pts who initially responded to IV induction with UST who were subsequently randomized into the maintenance study IM-UNITI to UST 90mg q8w (n=128), 90mg q12w (n=129), or PBO (n=131). Wk 56 is the first long-term extension visit 12 weeks after Wk 44 of IM-UNITI. Results: Compared to Wk 44, pts on UST therapy at Wk 56 maintained remission (50.8% for UST q8w, 49.6% for UST q12w; each p<0.001), while there was a noteworthy reduction in remission rates (27.5%) in PBO pts (Table 1). The number of pts in clinical remission not receiving corticosteroids at Wk 56 was significantly greater in UST therapy group vs. PBO (46.1% UST q8w, 43.4% UST q12w, 22.1% PBO; p<0.001). In a subgroup analysis of conventional therapy failure pts (UNITI-2), a greater proportion of pts treated with UST therapy achieved clinical remission that was maintained at Wk 56 from Wk 44 (Table 2) compared to PBO. Safety at Wk 56 was similar to the previous safety results reported for Wk 44 as no new safety events were observed. Discussion: In pts with moderate to severe CD who responded to induction therapy with UST, SC UST is significantly better at maintaining clinical remission vs PBO. Remission rates among UST pts is maintained from Wk 44 to Wk 56; yet, durable biologic effect seen from one IV induction dose seems to diminish more rapidly from Wk 44 to Wk 56.