Real-World Effectiveness and Safety of Tixagevimab-Cilgavimab: A Target Trial Emulation Study

OBJECTIVES: Immunocompromised individuals are at high risk of COVID-19 infection and mortality, yet have suboptimal responses to mRNA and inactivated COVID-19 vaccines. This study aims to evaluate the real-world effectiveness and safety of tixagevimab-cilgavimab for COVID-19 prophylaxis among immunocompromised individuals.

METHODS: Target trial emulation using territory-wide electronic health records in Hong Kong. Immunocompromised individuals aged ≥12 years were eligible. A sequence of trials was emulated for each day during the inclusion period, where each eligible tixagevimab-cilgavimab recipient was matched to 4 eligible controls based on age, sex, COVID-19 vaccination and infection status, baseline comorbidities and chronic medication use. The risks of COVID-19 infection, COVID-19 hospitalization, COVID-19 mortality, severe COVID-19 and adverse events were compared between tixagevimab-cilgavimab recipients and controls using Cox regression.

RESULTS: 746 tixagevimab-cilgavimab recipients and 2980 controls were included from 1 May to 30 November 2022. During a median follow-up of 60 days, 52 and 286 COVID-19 infections were observed among recipients and controls respectively. Tixagevimab-cilgavimab was associated with a significantly reduced risk of COVID-19 infection (HR 0.708, 95%CI: 0.527-0.951). No significant difference was observed for COVID-19-related hospitalization (HR 0.902, 95%CI: 0.562-1.449). Zero versus eight COVID-19 mortality cases and zero versus two severe COVID-19 cases were observed in recipients and controls respectively. Notably, risk reduction in COVID-19 infection was consistently observed in immunocompromised individuals who previously received with ≥3 COVID-19 vaccine doses or had prior COVID-19 infection. Absolute incidence for all adverse events were low (<1 per 10000-person-days), although this study had limited statistical power to detect rare safety events.

CONCLUSIONS: Tixagevimab-cilgavimab was effective in reducing COVID-19 infection among immunocompromised individuals during an Omicron outbreak. Findings were consistent among those who previously received COVID-19 vaccines or had COVID-19 infection history. Further studies are warranted to confirm its safety and effectiveness against severe COVID-19 in a larger real-world population.