In phase 3 studies of Ustekinumab ( Stelara ), a fully human monoclonal IL-12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment.
Efficacy through 92 weeks and safety through 96 weeks of IM-UNITI maintenance are reported.
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 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients.
Dose-adjustment to 90 mg every 8 weeks occurred in patients randomised to 90 mg every 12 weeks 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.
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 90 mg every 12 weeks ( 77.4% to 72.6% ), every 8 weeks ( 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 90 mg every 12 weeks and every 8 weeks groups and lower in patients with prior dose adjustment.
Proportions of patients in clinical remission at week 92 for all treated every 8 weeks ( 64.4% ) and every 12 weeks ( 64.3% ) groups were lower than randomised every 8 weeks ( 74.4% ) and every 12 weeks ( 72.6% ) groups, but similarly maintained.
Safety events ( per hundred patient-years ) were similar among all placebo and Ustekinumab patients ( week 0-96 ), 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.
In conclusion, subcutaneous Ustekinumab maintained clinical response and remission through week 92.
No new safety signals were observed. ( Xagena )
Sandborn WJ et al, Aliment Pharmacol Ther 2018; 48: 65-77