Ustekinumab treatment effectiveness in clinical practice-a multicentre retrospective review of long-term outcomes in Crohn's disease

Background: Recently published data demonstrated the efficacy of Ustekinumab (USK) in the treatment of moderate-severe Crohn's disease. This study aimed to evaluate the Irish experience of USK 2011-2016 Methods: A retrospective multicentre analysis of patients treated with USK was performed via the INITiative network, a national collaborative IBD research network. Data collected from 5 centres included patient and disease characteristics, surgical history, concomitant therapies, induction and escalation of therapy, surgery post-treatment and sustained benefit at 12 months. Results: 59 patients were included; data available n=54. Patient and disease characteristics as per Table 1. [Table Presented] Median duration of follow-up post-treatment = 17.4 months. 32/54 patients (59.3%) had prior Crohn's-related surgery; 28% pa-tients had >1 surgical procedure. All patients had been treated with >1 anti-TNF agent. 32 patients (35%) had failed therapy with 3 anti-TNF agents. Various induction regimens were utilised. All patients received sub-cutaneous (sc) induction; median cumulative induction dose=225mg (range 135-270mg). 29.6% (n=16) were taking concomitant im-munomodulators and 27.8% (n=15) concomitant steroids at induction. Most patients received 90mg maintenance dose; median interval of 8 weeks (range: 2-8weeks). In 17 cases (31.5%) USK therapy was escalated, usually by increasing dose frequency. Of those patients who were escalated 13 (76.5%) had a sustained clinical benefit at 12 months. 12 month follow-up data is available for 44 patients; 10 patients continue USK with treatment duration <12 months. The median treatment duration=359 days (IQR 101-956 days). 25/44 (56.8%) had sustained benefit at 12 months; 18 patients (72%) continued USK at the time of last follow-up. 23 patients had endoscopic assessment before and after induction therapy. 39% (n=9) demonstrated improvement; 5 patients achieved mucosal healing. 13/54 patients (24%) had surgery while on USK; n=9 within 12 months of induction. In a logistic regression model, failing to respond to 3 anti-TNF agents (primary non-response, loss of response, adverse event) was signif-icantly associated with requiring surgery in the 12 months post-induction (p=0.017). Conclusions: In this study, USK provided sustained benefit at 12 months to >50% patients with medically-refractory Crohn's disease. These data suggest that induction therapy with sc USK may be an alternative to iv induction. As with anti-TNF therapy, dose optimi-sation appears to be critical in inducing and maintaining response.