Effects of Remdesivir in Hospitalized Patients with COVID-19: Systematic Review and Individual Patient Data Meta-Analysis of Randomized Clinical Trials

Background: The evidence from randomized trials on remdesivir for hospitalized patients with coronavirus disease 2019 (COVID-19) is conflicting. We conducted a systematic review and individual patient data meta-analysis (IPDMA) to assess the benefits and harms of remdesivir compared to placebo or usual care in hospitalized patients and whether treatment effects differed in prespecified subgroups.Methods: We systematically searched electronic databases and registries through April 11th 2022. The primary outcome was all-cause mortality at day 28. We used multivariable hierarchical regression adjusting for respiratory support status, age, and enrollment period to investigate effect modifiers. PROSPERO (CRD42021257134). Findings: Out of nine eligible RCTs, six provided individual data of 3729 hospitalized COVID-19 patients recruited between February 2020 and January 2021. Within 28 days of randomization, 229 of 1886 patients (12.0%) assigned to remdesivir and 268 of 1780 (15.1%) assigned to no remdesivir died (adjusted odds ratio [aOR] 0.82; 95% confidence interval [CI], 0.67-1.00; p=0.054). We found evidence for a subgroup effect according to respiratory support status at baseline (interaction p=0.012): Of those ventilated including high-flow oxygen, 144/615 (23.4%) assigned to remdesivir died versus 146/630 (23.2%) assigned to no remdesivir (aOR 1.04 [0.79-1.38]; low certainty evidence). Of those receiving no or low flow oxygen, 85/1241 (6.8%) assigned to remdesivir died versus 122/1150 (10.6%) assigned to control (aOR 0.62 [0.46-0.83]; high certainty evidence). There was no evidence for a credible subgroup effect with respect to age, presence of comorbidities, time to start of remdesivir after symptom onset, C-reactive protein level, enrollment period, or presence of anti-SARS-CoV-2 antibodies. The frequency of severe or serious adverse events was not elevated with remdesivir.Interpretation: This IPDMA showed reduced mortality with remdesivir in hospitalized COVID-19 patients requiring no or conventional oxygen support, but not in patients already ventilated.Funding: EU-RESPONSE (grant number 101015736)Declaration of Interest: Dominique Costagliola reports an HIV grant from Janssen (2019-2020), personal fees from Gilead (2020) and Pfizer (2022) for lectures outside the submitted work. Matthias Briel reports an unrestricted grant from Moderna (2022) for a study outside the submitted work. Todd C. Lee reports receiving salary support from the Fonds de Recherche du Québec Santé. Maya Hites reports personal fees from Gilead (2020) and Pfizer (2021) for lectures outside the submitted work, and congress/travel fees from Pfizer (2021), and Gilead (2022). Inge C. Olsen reports funding from BerGenBio for a study outside the submitted work. All other authors have declared that no competing interests exist.