P704 Ustekinumab induces limited mucosal healing after 6 months in a real-life, prospective cohort of patients with refractory Crohn’s disease

• Published in: Journal of Crohn's and colitis 2018-01, Vol.12 (supplement_1), p.S467-S467
• Main Authors: Verstockt, B, Noman, M, Aerden, I, Peeters, M, Brouwers, E, Ballet, V, Vandersmissen, L, Van Assche, G, Gils, A, Vermeire, S, Ferrante, M
• Format: Article
• Language: English
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjx180.831

Abstract Background Ustekinumab (UST) was recently approved by FDA and EMA in Crohn’s disease (CD). Real-life data in patients IV induced with UST are currently lacking. We report efficacy of UST during induction and maintenance, including patient-reported outcome (PRO2), CRP, faecal calprotectin (fCal) and endoscopy (SES-CD). Additionally, we assess association between UST serum levels (SL) and outcome. Methods Forty-seven CD patients, all refractory to anti-TNF and vedolizumab, were prospectively included. All received UST 6 mg/kg IV at induction, with SC UST 90 mg q8w thereafter. Patients were endoscopically assessed at baseline and week 24. Clinical remission was defined as average daily stool frequency ≤2.8 and average abdominal pain score ≤1. Biochemical remission was defined as CRP ≤5 mg/l and response as CRP decrease of at least 50% or CRP ≤5 mg/l, in patients with elevated CRP at baseline. Endoscopic response was defined as ≥50% SES-CD decrease compared to baseline, mucosal healing as SES-CD ≤2. UST SL were measured using an in-house developed ELISA with similar performance as JnJ assay. Results All patients were prospectively followed up for a median of 24 (IQR 16–31) weeks. Twenty patients (43%) discontinued therapy after a median of 24 (19–24) weeks, all because of endoscopically confirmed primary non-response. Although SES-CD decreased from 14 (9–19) at baseline to 12 (7–16) at week 24 (p = 0.04), this resulted in low endoscopic response (19%) and mucosal healing (3%) rates. Overall fCal dropped significantly from baseline (1741 µg/g) to week 4 (1074 µg/g) and 8 (603 µg/g), whereafter it started to increase by week 16 (747 µg/g) and 24 (988 µg/g). CRP decreased from 17 to 6 mg/l at week 24 (p = 0.005), resulting in biological response and remission rates of 46% and 21%. Similarly, PRO2 dropped significantly, leading to a clinical remission rate of 26% by week 24. UST SL at week 8 (6.3, 2.7–9.3 µl/l) and 24 (1.6, 0.6–3.3 µl/l) showed substantial interindividual variability but correlated well between both time points (r = 0.7, p < 0.001). Week 8 and 24 SL were numerically higher in patients with endoscopic response and biological remission at week 24. Quartile analysis showed all biological remitters being in the upper quartiles, whereas the majority of non-remitters were in the lower. Patients with the highest fCal decrease were also in the upper quartiles. Healing rates were too low to determine predictive thresholds. Conclusions In biologics