Efficacy and Safety of Ustekinumab for Crohnʼs Disease: Results From IM-UNITI Long-Term Extension Through 3 Years: Presidential Poster Award

Abstract

Introduction: Ustekinumab (UST) is a mAB to IL 12/23p40 approved for treatment of moderate-tosevere active Crohn's disease (CD). The IM-UNITI long-term extension (LTE) evaluates efficacy and safety of subcutaneous (SC) UST through 5yrs, with results through wk156 (efficacy assessed at wk152) 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, n=132; or UST 90mg q8w, n=132). A one-time dose adjustment to 90mg q8w occurred in randomized pts who met loss of response criteria from wks8-32. Non-randomized pts included: PBO induction responders who continued PBO; PBO induction non-responders who received UST 130mg IV then UST 90mg SC q12w if in clinical response at wk8; and UST induction non-responders who received UST 90mg SC and if in clinical response at wk8, continued UST 90mg SC q8w. All pts who completed treatment through wk44 were eligible to enter the LTE continuing the same treatment. This included 567 UST pts, of which 237 were from the primary population. PBO pts discontinued treatment after study unblinding following Wk44 DBL. Efficacy was assessed q12wks prior to study unblinding and then at UST dosing visits. Results: Discontinuation of study agent prior to wk156 occurred in 29.6% of 567 UST pts. Table 1 presents analyses for randomized pts who entered LTE. Among all UST pts, remission rates at wk152 were 56.3% & 55.1% for q12w and q8w, respectively. In an ITT analysis of randomized pts from maintenance wk 0-152, 38% (49/129) of UST induction responder q12w pts and 43%(55/128) of q8w pts were in remission at wk152. Antibody to UST rates through wk156 remained low, occurring in 4.0%(8/202) of randomized pts continuously receiving UST and 4.8%(27/567) of all pts treated with UST. Safety events (per 100 pt-yrs) were not higher among all UST pts entering LTE compared to PBO from wk44-156, including AE's (325.26 vs 358.8), SAEs (19.4 vs 23.11), and serious infections (4.14 vs 4.62), with 1061.6 pt-yrs of follow-up among UST pts and 173.1 pt-yrs of follow-up among PBO pts. Among all UST pts, 3 deaths (ESRD, acute MI, sepsis) and 2 non-NMSC malignancies (adenocarcinoma of small intestine and CML) were reported from wks 96-156. Conclusion: SC UST maintained clinical response and remission through 3yrs in a substantial proportion of pts, particularly those naïve to anti-TNFs. UST was well-tolerated through 3yrs with no new safety signals.604 Figure 1. IM-UNITI Efficacy Assessments at Week 152 Among Randomized Patients who entered LTE