Su1971 REAL-WORLD EFFECTIVENESS AND SAFETY OF USTEKINUMAB FOR THE TREATMENT OF CROHNS DISEASE: THE SCOTTISH USTEKINUMAB COHORT

Introduction Ustekinumab (UST) is an anti-IL12/23 biologic licensed for the treatment of moderate to severe Crohn’s disease (CD). The aims of this study were to establish the long-term real-world effectiveness and safety of UST for the treatment of CD in a large UK cohort. Methods This was a multicentre retrospective cohort study including 8 NHS health-boards in Scotland. Patients treated with UST between Nov 2015 and Jun 2019 were identified. Inclusion criteria included: a diagnosis of CD; active symptoms attributed to CD with objective evidence of mucosal inflammation (CRP >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/MRI); completion of standard induction; week 8 review ± further follow up. Clinical assessments were performed based on physician global assessment (response was defined as ≥50% reduction in CD-related symptoms and remission defined as complete resolution of all CD-related symptoms). Mucosal healing was defined as absence of ulceration/erosions on ileo-colonoscopy or no inflammation on MRI if ileo-colonoscopy was not possible (eg. B2 disease). Deep remission was defined as clinical remission plus mucosal healing. Perianal response was determined by follow up MRI (reduction in enhancement, closure or fibrosis of tract compared to baseline MRI). Rates of serious adverse events (discontinuation of UST, hospitalisation or death) during follow up were described quantitively. Results A total of 216 patients (57.9% female; median age 39.0 years, IQR 28.8–51.8; median disease duration 9.9 years, IQR 6.0–16.5) with a median follow up of 35.0 weeks (IQR 17.4–52.0) were included. The majority of patients had ileo-colonic disease (L1, 19.9%; L2, 23.1%; L3, 56.9%) and an inflammatory phenotype (B1, 43.1%; B2, 41.2%; B3, 15.7%). A total of 98.6% of patients had previously been exposed to a biologic and 55.1% had undergone previous surgery. Seventy-one percent of patients received 8-weekly maintenance dosing, whilst 25.5% and 40.7% of patients were also receiving an immunomodulator and/or steroids at initiation, respectively. At week 8, clinical response and remission rates were 45.4% and 6.0%, respectively. Twelve-month cumulative rates of clinical remission, mucosal healing (n=123) and deep remission (n=123) were 32.0%, 32.7% and 19.3%, respectively (figure 1). In patients with active perianal disease at initiation (n=37), 12-month cumulative rates of perianal response were 53.1%. During 140 patient years of follow up (PYF), 19 patients experienced a serious adverse event (13.6 per 100 PYF). Conclusions We have shown in a large real-world cohort of complex, treatment refractory CD patients that UST is a safe and effective treatment option