Tocilizumab vs. Sarilumab Among Adults Hospitalized Due to COVID-19: A Federated Comparative Effectiveness Study Across England and Scotland Under the Target Trial Emulation Framework
Author(s)
Bang Zheng, PhD1, Amanj Kurdi, Prof2, Alain Amstutz, MD PhD3, Amelia Green, PhD4, Emily Herrett, PhD1, John Tazare, PhD1, Qing Wen, PhD1, Viyaasan Mahalingasivam, MPhil1, Rebecca Smith, PhD4, Brian MacKenna, MPharm4, Amir Mehrkar, MRCGP4, Seb Bacon, BA4, Ben Goldacre, Prof4, Chris Robertson, Prof2, Aziz Sheikh, Prof4, Laurie Tomlinson, Prof1.
1London School of Hygiene and Tropical Medicine (LSHTM), London, United Kingdom, 2University of Strathclyde, Glasgow, United Kingdom, 3Bristol Medical School : Population Health Sciences, Bristol, United Kingdom, 4University of Oxford, Oxford, United Kingdom.
1London School of Hygiene and Tropical Medicine (LSHTM), London, United Kingdom, 2University of Strathclyde, Glasgow, United Kingdom, 3Bristol Medical School : Population Health Sciences, Bristol, United Kingdom, 4University of Oxford, Oxford, United Kingdom.
OBJECTIVES: Tocilizumab and sarilumab, two interleukin-6 (IL-6) inhibitors commonly used in rheumatoid arthritis, have also been evaluated for severe COVID-19. While strong evidence supports tocilizumab’s clinical benefits, evidence for sarilumab remains limited, leading to inconsistent guideline recommendations. No studies have assessed the two IL-6 inhibitors during the delta/omicron SARS-CoV-2 variant periods. We aimed to compare the effectiveness of tocilizumab and sarilumab among adults hospitalised due to COVID-19 across England and Scotland between July 2021 and February 2022, when delta/omicron were prevalent and both drugs frequently prescribed.
METHODS: We conducted a population-based cohort study using electronic health records data through the OpenSAFELY-TPP platform (England) and EAVE II (Scotland). Following the target trial emulation framework, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the two IL-6 inhibitors with regards to 28-day all-cause mortality and time to hospital discharge.
RESULTS: We identified 9740 eligible patients in England and 747 in Scotland treated with an IL-6 inhibitor for COVID-19 during the study period. In England, 820 (20.4%) of 4025 participants receiving sarilumab died by day 28 compared with 1150 (20.1%) of 5710 participants receiving tocilizumab (adjusted HR 1.07, 95% CI 0.96-1.19). In Scotland, 113 (31.5%) of 359 participants in the sarilumab group died by day 28 compared with 129 (33.0%) of 388 participants in the tocilizumab group (adjusted HR 0.89, 95% CI 0.67-1.18). There was no evidence of a difference in time to hospital discharge between the groups and results remained robust in sensitivity analyses. We found no credible effect modification by variant of concern, vaccination status, age, sex, ethnicity, BMI, or comorbidities.
CONCLUSIONS: In this large-scale comparative effectiveness study during the delta/omicron period across two UK nations, we found no significant difference in effectiveness between tocilizumab and sarilumab in terms of mortality and time to hospital discharge among adults hospitalised due to COVID-19.
METHODS: We conducted a population-based cohort study using electronic health records data through the OpenSAFELY-TPP platform (England) and EAVE II (Scotland). Following the target trial emulation framework, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the two IL-6 inhibitors with regards to 28-day all-cause mortality and time to hospital discharge.
RESULTS: We identified 9740 eligible patients in England and 747 in Scotland treated with an IL-6 inhibitor for COVID-19 during the study period. In England, 820 (20.4%) of 4025 participants receiving sarilumab died by day 28 compared with 1150 (20.1%) of 5710 participants receiving tocilizumab (adjusted HR 1.07, 95% CI 0.96-1.19). In Scotland, 113 (31.5%) of 359 participants in the sarilumab group died by day 28 compared with 129 (33.0%) of 388 participants in the tocilizumab group (adjusted HR 0.89, 95% CI 0.67-1.18). There was no evidence of a difference in time to hospital discharge between the groups and results remained robust in sensitivity analyses. We found no credible effect modification by variant of concern, vaccination status, age, sex, ethnicity, BMI, or comorbidities.
CONCLUSIONS: In this large-scale comparative effectiveness study during the delta/omicron period across two UK nations, we found no significant difference in effectiveness between tocilizumab and sarilumab in terms of mortality and time to hospital discharge among adults hospitalised due to COVID-19.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO252
Topic
Clinical Outcomes, Health Technology Assessment, Methodological & Statistical Research
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Infectious Disease (non-vaccine), Respiratory-Related Disorders (Allergy, Asthma, Smoking, Other Respiratory)