The following is a summary of “Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study,” published in the July 2024 issue of Infectious Disease by Choi et al.

Researchers conducted a retrospective study to compare the safety and effectiveness of combining remdesivir and nirmatrelvir-ritonavir versus using each drug alone in hospitalized adults with COVID-19.

They conducted a target trial emulation study using electronic health records from Hong Kong patients aged 18 or older. Patients received either a combination of nirmatrelvir–ritonavir and remdesivir or monotherapy with either drug (March 16 to December 31, 2022) within 5 days of hospitalization for COVID-19. Inverse probability of treatment weighting was used to balance patient characteristics across groups. The study aimed to compare the risk of all-cause mortality, ICU admission, or ventilatory support over 90 days using Cox proportional hazards regression adjusting for weighting.

The results showed 18,196 participants from electronic health records receiving remdesivir (n=4232), nirmatrelvir–ritonavir (n=13,656), or nirmatrelvir–ritonavir and remdesivir (n=308) from  March 16 and December 31, 2022. Using inverse probability of treatment weighting, the weighted sample comprised 18,410 recipients of nirmatrelvir–ritonavir and remdesivir, 18,178 recipients of remdesivir monotherapy, and 18,287 recipients of nirmatrelvir–ritonavir monotherapy. Following a median follow-up of 84 days (IQR 45–90), nirmatrelvir–ritonavir monotherapy (HR 0.18 [95% CI 0.15–0.20]; ARR –16.33% [95% CI –16.98 to –15.68]) and nirmatrelvir–ritonavir and remdesivir combination therapy (HR 0.66 [95% CI 0.49–0.89]; ARR –6.52% [95% CI –7.29 to –5.74]) were associated with lower mortality risk compared to remdesivir monotherapy. Similar trends were observed for ICU admission or ventilatory support (nirmatrelvir–ritonavir monotherapy: HR 0.09 [95% CI 0.07–0.11]; ARR –10.04% [95% CI –10.53 to –9.56]; combination therapy: HR 0.68 [95% CI 0.42–1.12]; ARR –3.24% [95% CI –3.84 to –2.64]). Nirmatrelvir–ritonavir monotherapy exhibited lower risk of mortality (HR 0.27 [95% CI 0.20–0.37]; ARR –9.81% [95% CI –10.39 to –9.24]) and ICU admission or ventilatory support (HR 0.13 [95% CI 0.08–0.22]; ARR –6.80% [95% CI –7.22 to –6.39]) compared to combination therapy.

Investigators concluded that nirmatrelvir-ritonavir alone might be as effective, or even more effective, in reducing mortality and the need for intensive care compared to regimens containing remdesivir.

Source: thelancet.com/journals/laninf/article/PIIS1473-3099(24)00353-0/fulltext#%20