656 Ustekinumab Dose Escalation Is Effective in Treatment of Crohn's Disease

Abstract

INTRODUCTION: Ustekinumab (UST) is approved for moderate to severe Crohn's disease (CD) at 90 mg every 8 week dose for maintenance. However, there is limited data about the benefit of UST dose escalation. The aim of this study was to evaluate the response to UST dose escalation in a real-world cohort of active CD patients. METHODS: CD patients who had partial or no clinical response to standard UST induction and/or maintenance and required dose escalation to 90 mg every 4 or 6 weeks from 2016 to 2018 at a tertiary IBD referral center were retrospectively identified. Patients who did not receive UST intravenous induction dose or had clinically inactive disease at the time of dose escalation were excluded. Response and remission were defined based on physician global assessment. Primary outcome was clinical response to dose escalation. Secondary outcomes were clinical remission and endoscopic response to dose escalation. Multivariable regression with backward elimination was performed to identify predictors of clinical response to UST dose escalation. RESULTS: A total of 68 patients received UST dose escalation, median age of the cohort was 39 years, 56% of patients were females. The majority (51.5%) had ileocolonic disease. 57.4% had stricturing disease, and 39.7% had non-stricturing non-penetrating disease. 54.4% had a prior surgical resection. Prior medication exposure included: immunomodulators (78%), anti-TNF (95.3%) and anti-integrin drugs (46.9%). Overall, 67.8% of patients had clinical response at week 8 after UST induction dose. Following UST dose escalation, 79.4% of patients had a clinical response and 30.9% achieved clinical remission within 3-6 months. Of the patients with available endoscopic follow-up data (n = 39), 59% had endoscopic response, and 20.5% achieved endoscopic remission. Baseline characteristics between responders and non-responders to UST dose escalation were similar except for a higher proportion of responders having had clinical response to UST induction dose (Table 1). On multivariable regression analysis, response to UST induction therapy was the only independent predictor of response to UST dose escalation (OR 7.01; 95% CI 1.83-27.07; P = 0.005). CONCLUSION: A majority of patients with moderate to severe CD benefited from UST dose escalation suggesting the clinical utility of optimizing dosing in the treatment course. Response to UST induction dose may be a strong predictor of subsequent response to UST dose escalation.