A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2.

Background: Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95). Methods: ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ≥2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay. Results: Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70-1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27-1.12; p=0.26), while the OR was 0.31 (80% CI 0.09-1.06) in patents with high baseline serum IL-33/sST2 complex levels. Conclusions: Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.

Hepatitis C standards of care: A review of good practices since the advent of direct-acting antiviral therapy.

Significant steps must be taken to reduce the global incidence and prevalence of hepatitis C virus (HCV) and mortality from HCV infection to achieve the WHO goal of eliminating viral hepatitis as a public health threat by 2030. Proper epidemiological surveillance of the full continuum of care is essential for monitoring progress and identifying gaps that need to be addressed. The tools required for elimination have largely been established, and the issue at hand is more how they should best be implemented in different settings around the world. Documenting good practices allows for knowledge exchange to prevent transmission and improve health outcomes for people with HCV. This review found 13 well documented HCV good practices that have become the standard of care or that should become the standard of care as soon as possible. In 2013, highly effective direct-acting antiviral therapy became available, which has cure rates of over 95%. Together with this new therapy, evidence-based good practices can help countries eliminate viral hepatitis C.