Sandborn W, Feagan BG, Gasink C, et al (2016) A phase 3 randomized, multicenter, double-blind, placebo-controlled study of ustekinumab maintenance therapy in moderate–severe Crohn’s disease patients: Results from IM-UNITI. Gastroenterology AGA abstract 768

Abstract

Single-dose intravenous (IV) ustekinumab (UST) induced response and remission in Crohn’s disease (CD) patients refractory to TNF antagonists (UNITI-1) and failing conventional therapies (UNITI-2). The objective of this study was to evaluate the safety and efficacy of two subcutaneous (SC) UST regimens as maintenance therapy. We conducted a phase 3, double-blind, placebo-controlled maintenance trial (IM-UNITI) in moderate-to-severe CD patients who achieved clinical response at week 8 in one of two UST IV induction studies. The primary study population (N = 388) was randomly assigned to groups given SC injections of placebo (PBO), or UST 90 mg every 8 weeks (q8w) or every 12 weeks (q12w). The primary endpoint was clinical remission at week 44; major secondary endpoints included clinical response, clinical remission among patients in remission at baseline, corticosteroid free remission, and clinical remission in patients refractory or intolerant to TNF antagonists (UNITI-1 subpopulation), all at week 44. A significantly greater proportion of patients in the UST groups were in clinical remission at week 44 compared with PBO (53.1% and 48.8% in the q8w and q12w groups vs. 35.9% on PBO; P = 0.005 and P = 0.040, respectively). The treatment effect difference for q8w vs. PBO (17.2%, [95% confidence interval or CI: 5.32%, 29.71%]) was numerically higher than the q12w group (13.0%, [95% CI: 1.05%, 24.87%]. Significantly greater proportions of patients also maintained clinical response at week 44 in the q8w (59.4%) and q12w (58.1%) UST groups vs. PBO (44.3%; P < 0.05 for both). The proportions of patients in clinical remission and not receiving concomitant corticosteroids at week 44 were significantly higher in the q8w group (46.9%) and numerically higher in the q12w group (42.6%) vs. placebo (29.8%; P = 0.004 and nominal P = 0.035, respectively). Primary, major, and other secondary endpoints in notable subsets are in Fig. 1. Similar proportions of patients with adverse events were seen across treatment groups (81.7% and 80.3% for q8w and q12w vs. 83.5% PBO). The proportions of patients with serious adverse events were 9.9%, 12.2%, and 15.0% among the q8w, q12w, and PBO groups. Serious infections occurred in 2.3%, 5.3%, and 2.3% of patients in the q8w, q12w, and PBO groups. Among the primary population, no deaths or major adverse cardiovascular events were reported, and two patients reported malignancies (one basal cell carcinoma in each of the PBO and q8w groups). UST 90 mg q8w and q12w maintained clinical response and remission among patients with moderate-to-severe CD who were induced into clinical response with IV UST, with a favorable safety profile through week 44. The q8w regimen more consistently demonstrated efficacy than the q12w regimen across the range of endpoints.