Tocilizumab versus sarilumab among adults hospitalised with COVID-19 : target trial emulation across England and Scotland

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Zheng, Bang and Kurdi, Amanj and Amstutz, Alain and Green, Amelia and Herrett, Emily and Tazare, John and Wen, Qing and Mahalingasivam, Viyaasan and Smith, Rebecca and MacKenna, Brian and Mehrkar, Amir and Bacon, Sebastian and Goldacre, Ben and Robertson, Chris and Sheikh, Aziz and Tomlinson, Laurie (2026) Tocilizumab versus sarilumab among adults hospitalised with COVID-19 : target trial emulation across England and Scotland. Nature Communications. ISSN 2041-1723 (https://doi.org/10.1038/s41467-026-73134-9)

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Abstract

The interleukin-6 (IL-6) inhibitors tocilizumab and sarilumab have been repurposed for COVID-19 treatment. However, discrepancies still exist across global and national COVID-19 guidelines, with limited data on the comparative effectiveness between these therapeutics especially during the delta/omicron periods. With the approval of NHS England and Public Health Scotland, we compared their effectiveness among adults hospitalised with COVID-19 using electronic health records data through the OpenSAFELY-TPP (England) and EAVE II (Scotland) platforms. Following the target trial emulation framework, 10,487 patients treated between July 2021 and February 2022, when both drugs were frequently prescribed, were included. In England, 1150 (20.1%) of 5710 participants receiving tocilizumab died by day 28 compared with 820 (20.4%) of 4025 participants receiving sarilumab (adjusted hazard ratio [aHR] 1.07, 95% CI 0.96-1.19). In Scotland, 114 (29.4%) of 388 participants receiving tocilizumab died by day 28 compared with 97 (27.0%) of 359 participants receiving sarilumab (aHR 0.92, 95% CI 0.68-1.23). There was no evidence of a difference in time to hospital discharge between the groups, and no credible effect modification by variant of concern, vaccination status, age, sex, ethnicity, body mass index, or comorbidities. Our findings provide supportive evidence for both drugs as alternative therapeutic options in COVID-19 in-patient management.

ORCID iDs

Zheng, Bang, Kurdi, Amanj ORCID logoORCID: https://orcid.org/0000-0001-5036-1988, Amstutz, Alain, Green, Amelia, Herrett, Emily, Tazare, John, Wen, Qing, Mahalingasivam, Viyaasan, Smith, Rebecca, MacKenna, Brian, Mehrkar, Amir, Bacon, Sebastian, Goldacre, Ben, Robertson, Chris, Sheikh, Aziz and Tomlinson, Laurie;
CORE (COnnecting REpositories)