Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy

Background: In Phase 3 studies of ustekinumab, a fully human monoclonal IL-12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8weeks of induction and 44weeks of maintenance treatment. Efficacy through 92weeks and safety through 96weeks of IM-UNITI maintenance are reported. Methods: UNITI-1 (TNF-antagonist failures) and UNITI-2 (conventional therapy failures) patients (N=1281) entered IM-UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90mg every 12weeks, every 8weeks, or placebo and 884 nonrandomised patients. Dose-adjustment to 90mg every 8weeks occurred in patients randomised to 90mg every 12weeks and placebo patients with loss of response (Weeks 8-32). All Week 44 completers could enter the long-term extension without further dose adjustment. Placebo patients discontinued following study unblinding. Results: A total of 718 patients (all treated) entered the long-term extension (298 randomised and 420 not randomised). Overall, 86.5% (621/718) completed Week 96. The proportions of randomised patients in clinical remission were generally maintained from Week 44 through 92 in ustekinumab 90mg every 12weeks (77.4% to 72.6%), every 8weeks (84.1% to 74.4%), and prior dose adjustment groups (63.4% to 53.5%). At Week 92, the proportions of patients in clinical remission were similar in the ustekinumab 90mg every 12weeks and every 8weeks groups and lower in patients with prior dose adjustment. Proportions of patients in clinical remission at Week 92 for all treated every 8weeks (64.4%) and every 12weeks (64.3%) groups were lower than randomised every 8weeks (74.4%) and every 12weeks (72.6%) groups, but similarly maintained. Safety events (per hundredpatient-years) were similar among all placebo and ustekinumab patients (Week0-96), including adverse events (484.39 vs 447.76), serious adverse events (19.24 vs 18.82), and serious infections (4.09 vs 4.02). No dose effect was observed. Conclusions: Subcutaneous ustekinumab maintained clinical response and remission through Week 92. No new safety signals were observed.