Background: Ustekinumab (UST) is a fully human IGG1 mAB to human IL 12/23p40 approved for treatment of moderate to severe active Crohn's disease (CD). The ongoing IM-UNITI long-term extension (LTE) evaluates efficacy & safety of subcutaneous (SC) UST through approximately 5 years of treatment, with results through wk96 reported herein.
Methods: 1281 patients (pts) entered the maintenance study, including 397 UST induction responders in the primary population (randomized to SC placebo (PBO); n=133, UST 90mg q12w (q12w); n=132, or UST 90mg q8w (q8w); n=132). A one-time dose adjustment to 90mg q8w occurred in pts in the randomized group who met loss of response criteria between wks8 & 32. Non-randomized pts included: PBO induction responders who continued on PBO, non-responders to PBO induction who received a single UST 130mg IV dose then UST 90mg SC q12w if in clinical response at wk8, & non-responders to UST induction who received UST 90mg SC & if in clinical response at wk8 continued on UST 90 mg q8w. All pts completing wk44 were eligible to enter LTE continuing on the treatment they were on at wk44. This included 567 UST treated pts of which 237 were from the primary population. Pts receiving PBO were discontinued following the unblinding of the entire study, which occurred after the Week 44 DBL.
Results: Table 1 presents analyses for randomized pts where pts with missing data or who discontinued are assumed not to be in response or remission at wk92, with 72.6% of q12w pts & 74.4% of q8w pts (non-dose adjusted) achieving remission at wk92. Based on observed data analyses, among randomized pts who continued to receive UST through wk96, 79.2% of q12w & 87.1% of q8w pts (non-dose adjusted) were in remission & 90.9% & 94.3% were in response at wk92, respectively. Among all UST treated pts who continued to receive UST through wk96, remission & response rates at wk92 were 70.7% & 84.7%.
Safety events (per hundred subject years) were not higher among all UST treated pts compared to PBO from wk44 through wk96, including overall AE's (82.9 vs 91), SAE's (14.16 vs 18.2), & serious infections (3.73 vs 4.33), with 536.8 subject years of follow-up among UST treated pts & 115.4 subject years among PBO pts. Among all UST treated pts, there were 2 deaths (sudden death, asphyxia). There were two non-NMSC malignancies reported between wks44 & 96, a seminoma (UST) & a papillary thyroid cancer (PBO only).
Conclusions: SC UST maintained clinical response & remission through two years. No new safety signals were observed.