Real-world effectiveness of early remdesivir and sotrovimab in the highest-risk COVID-19 outpatients during the Omicron surge

Piccicacco et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkac256

Aug 2022

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Retrospective high-risk outpatients in the USA, 82 treated with remdesivir, 88 with sotrovimab, and 90 control patients, showing significantly lower combined hospitalization/ER visits with both treatments in unadjusted results. The dominant variant was omicron B.1.1.529.

Gérard, Zhou, Wu, Kamo, Choi, Kim show significantly increased risk of acute kidney injury with remdesivir.

Remdesivir efficacy disappears with longer followup. Mixed-effects meta-regression of efficacy as a function of followup duration across all remdesivir studies shows decreasing efficacy with longer followup7. This may reflect antiviral efficacy being offset by serious adverse effects of treatment.

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Study covers remdesivir and sotrovimab.

risk of death, 65.6% lower, RR 0.34, p = 1.00, treatment 0 of 82 (0.0%), control 1 of 90 (1.1%), NNT 90, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 29.

risk of hospitalization, 30.2% lower, RR 0.70, p = 0.47, treatment 7 of 82 (8.5%), control 11 of 90 (12.2%), NNT 27, day 29.

risk of hospitalization/ER, 52.5% lower, RR 0.48, p = 0.05, treatment 9 of 82 (11.0%), control 21 of 90 (23.3%), NNT 8.1, odds ratio converted to relative risk, day 29.

risk of progression, 78.0% lower, RR 0.22, p = 0.03, treatment 2 of 82 (2.4%), control 10 of 90 (11.1%), NNT 12, day 29.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

1. Gérard et al., Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database, Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2145.wiley.com, doi.org.

2. Zhou et al., Acute Kidney Injury and Drugs Prescribed for COVID-19 in Diabetes Patients: A Real-World Disproportionality Analysis, Frontiers in Pharmacology, doi:10.3389/fphar.2022.833679.frontiersin.org, doi.org.

3. Wu et al., Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS, Frontiers in Pharmacology, doi:10.3389/fphar.2022.692828.frontiersin.org, doi.org.

4. Kamo et al., Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure, In Vivo, doi:10.21873/invivo.13637.iiarjournals.org, doi.org.

5. Choi et al., 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, The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00353-0.sciencedirect.com, doi.org.

6. Kim et al., Investigating the Safety Profile of Fast‐Track COVID‐19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study, Pharmacoepidemiology and Drug Safety, doi:10.1002/pds.70043.wiley.com, doi.org.

7. c19early.org, c19early.org/smeta.html.c19early.org/smeta.html.

Piccicacco et al., 1 Aug 2022, retrospective, USA, peer-reviewed, 7 authors, study period 27 December, 2021 - 4 February, 2022, average treatment delay 4.0 days, ER visit. Contact: npiccicacco@tgh.org.

This Paper Remdesivir All

Real-world effectiveness of early remdesivir and sotrovimab in the highest-risk COVID-19 outpatients during the Omicron surge

Nicholas Piccicacco, Kristen Zeitler, Austin Ing, Jose Montero, Jonathan Faughn, Suzane Silbert, Kami Kim

Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkac256

Background: Remdesivir and sotrovimab both have clinical trial data in the outpatient setting demonstrating reduction in the risk of hospitalizations and emergency department (ED) visits related to COVID-19. Objectives: To evaluate the effectiveness of remdesivir in comparison with sotrovimab and matched high-risk control patients in preventing COVID-19-related hospitalizations and ED visits during the Omicron B.1.1.529 surge. Patients and methods: This retrospective cohort study included outpatients positive for SARS-CoV-2, with nonsevere symptoms for ≤7 days and deemed high-risk for severe COVID-19 by an internal scoring matrix. Patients who received remdesivir or sotrovimab from 27/12/2021 to 04/02/2022 were included (n = 82 and n = 88, respectively). These were compared with a control cohort of high-risk COVID-19 outpatients who did not receive therapy (n = 90). The primary outcome was a composite of 29 day COVID-19-related hospitalizations and/or ED visits. Pre-specified secondary outcomes included components of the primary endpoint, 29 day all-cause mortality and serious adverse drug events. Results: Patients treated with remdesivir were significantly less likely to be hospitalized or visit the ED within 29 days from symptom onset (11% versus 23.3%; OR = 0.41, 95% CI = 0.17-0.95). Patients receiving sotrovimab were also less likely to be hospitalized or visit the ED (8% versus 23.3%; OR = 0.28, 95% CI = 0.11-0.71). There was no difference in the incidence of hospitalizations/ED visits between sotrovimab and remdesivir. Conclusions: Our highest-risk outpatients with Omicron-related COVID-19 who received early sotrovimab or remdesivir had significantly lower likelihoods of a hospitalization and/or ED visit.

Author contributions Concept and design: N.P., K.Z., A.I. and J.M. Acquisition, analysis or interpretation of data: N.P., K.Z., A.I. and J.M. Drafting of manuscript: N.P., A.I., K.Z., J.F. and S.S. Critical revision of the manuscript for important intellectual content: K.K. and J.M. Statistical analysis: N.P. and K.Z. Supplementary data Table S1 is available as Supplementary data at JAC Online.

References

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Bhimraj, Morgan, Shumaker, IDSA Guidelines on the Treatment and Management of Patients with COVID-19

Fda, FDA Takes Actions to Expand Use of Treatment for Outpatients With Mild-to-Moderate COVID-19

Gottlieb, Vaca, Paredes, Early remdesivir to prevent progression to severe Covid-19 in outpatients, N Engl J Med, doi:10.1056/NEJMoa2116846

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Lee, Wong, Chai, Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis, BMJ, doi:10.1136/bmj-2021-068632

Peters, Rabinstein, Dubrock, Use of remdesivir in myasthenia gravis and COVID-19, Pharmacotherapy, doi:10.1002/phar.2524

Piccicacco, Zeitler, Montero, Effectiveness of severe acute respiratory syndrome coronavirus 2 monoclonal antibody infusions in high-risk outpatients, Open Forum Infect Dis, doi:10.1093/ofid/ofab292

Planas, Saunders, Maes, Considerable escape of SARS-CoV-2 Omicron to antibody neutralization, Nature, doi:10.1038/s41586-021-04389-z

Razonable, Ganesh, Bierle, Clinical prioritization of antispike monoclonal antibody treatment of mild to moderate Outpatient remdesivir versus sotrovimab for Omicron COVID-19, Mayo Clin Proc, doi:10.1016/j.mayocp.2021.11.017

Stolle, Nalamasu, Pergolizzi, Fact vs fallacy: the anti-vaccine discussion reloaded, Adv Ther, doi:10.1007/s12325-020-01502-y

Tseng, Ackerson, Luo, Effectiveness of mRNA-1273 against SARS-CoV-2 Omicron and Delta variants, Nat Med, doi:10.1038/s41591-022-01753-y

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