The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results from the SUCCESS Consortium.

Overview

abstract

OBJECTIVE: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study utilized a retrospective, multicenter, multinational, consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remission were assessed using time-to-event and clinical predictors were assessed by multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1113 patients (51.8% female, 90% prior anti-TNF exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remission at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naïve patients achieved significantly higher rates of clinical and endoscopic remission at 63% and 55%, respectively. On multivariable analyses, prior anti-TNF (HR, 0.72; 95% CI, 0.49-0.99) and vedolizumab exposure (HR, 0.65; 95% CI, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77/102 (75%) underwent dose optimization, and 44/77 (57%) achieved clinical response. An additional 152/681 (22.3%) patients were dose optimized as a result of primary non- or incomplete response to UST, of whom 40.1% (61/152) responded. Serious infections occurred in 3.4% of patients, while other non-infectious adverse events [lymphoma (n=1), arthralgia (n=6), rash (n=6), headache (n=3), hepatitis (n=3), hair loss (n=3), neuropathy (n=1), and vasculitis (n=1)] occurred in 2.4% of patients. CONCLUSIONS: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in bio-naive patients, and dose escalation may recapture clinical response.