Real-world effectiveness and safety of ustekinumab for the treatment of Crohn's disease: the Scottish ustekinumab cohort.

BACKGROUND AND AIM: Ustekinumab is a monoclonal antibody that targets interleukin-12/23. In Scotland, it was approved for the treatment of moderate to severe Crohn's disease in 2017. The objective of this study was to establish the real-world effectiveness and safety of ustekinumab in the treatment of Crohn's disease. METHODS: We conducted a retrospective study of patients receiving ustekinumab across eight Scottish National Health Service health boards between 2017 and 2019. Inclusion criteria included a diagnosis of Crohn's disease with symptoms attributed to active disease plus objective signs of inflammation at baseline (C-reactive protein ≥ 5 mg/L or fecal calprotectin ≥ 250 µg/g or inflammation on endoscopy/magnetic resonance imaging) and completion of induction plus at least one clinical follow-up at 8 weeks. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, deep remission, and perianal fistula response. Rates of serious adverse events were described quantitatively. RESULTS: Our cohort consisted of 216 patients (female sex, 37.9%; median age, 39.0 years, interquartile range [IQR] 28.8-51.8 years; disease duration, 9.9 years, IQR 6.0-16.5 years; prior biologic, 98.6%) with a median follow-up of 35.0 weeks (IQR 17.4-52.0 weeks). Twelve-month cumulative rates of clinical remission, mucosal healing, and deep remission (clinical remission plus mucosal healing) were 32.0%, 32.7%, and 19.3%, respectively. In patients with active perianal disease (n = 37), the 12-month cumulative perianal response rate was 53.1%. The serious adverse event rate was 13.6 per 100 patient-years of follow-up. CONCLUSION: Ustekinumab is a safe and effective treatment for the treatment of complex Crohn's disease.

Recent advances in alcoholic hepatitis.

Alcoholic hepatitis (AH) is an acute deterioration in liver function seen in the context of prolonged excessive alcohol consumption and is characterised by the rapid onset of jaundice. The diagnosis of AH has been controversial for many years: it is now accepted that there are clear clinical criteria which can be used to diagnose AH without the need for a liver biopsy. Corticosteroids remain the only treatment proven to be effective in reducing short-term mortality in severe AH; abstinence from alcohol is the most important factor in determining long-term survival. It is recommended a trial of corticosteroid therapy is considered only in those patients with high baseline 'static' scores (Glasgow Alcoholic Hepatitis score and model for end-stage liver disease). Response to corticosteroid therapy should be assessed using a 'dynamic' score such as the Lille score at day 7, with corticosteroids continuing only in patients with a favourable score. Infection and acute kidney injury are associated with poorer outcomes in AH. Early screening for and treatment of infection is recommended with antibiotic therapy overlapping with any subsequent corticosteroid treatment. A biomarker which predicts benefit from corticosteroids at baseline would avoid a trial of therapy to determine response. More efficacious therapeutic options for AH patients are required with N-acetylcysteine, granulocyte colony stimulating factor, faecal microbiota transplantation and routine antibiotics showing promise, but adequate controlled trials are needed to confirm efficacy. Liver transplant has an emerging role for some patients with severe AH not responding to corticosteroids and is likely to become more acceptable with improved methods of patient selection.