All Studies Meta Analysis

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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Sotrovimab for COVID-19

41st treatment shown to reduce risk in May 2023, now with p = 0.002 from 25 studies, recognized in 38 countries. Efficacy is variant dependent.

Lower risk for mortality, ICU, and hospitalization.

No treatment is 100% effective. Protocols combine treatments.

5,100+ studies for 112 treatments. c19early.org

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.

Efficacy is variant dependent. In Vitro studies predict lower efficacy for BA.11-3, BA.4, BA.54, XBB.1.9.3, XBB.1.5.24, XBB.2.9, CH.1.15, and no efficacy for BA.26, XBB, XBB.1.5, ХВВ.1.9.17, XBB.1.16, BQ.1.1.45, and CL.15. US EUA has been revoked.

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Study covers remdesivir and sotrovimab.

risk of death, 66.4% lower, RR 0.34, p = 1.00, treatment 0 of 88 (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, 34.9% lower, RR 0.65, p = 0.46, treatment 7 of 88 (8.0%), control 11 of 90 (12.2%), NNT 23, day 29.

risk of hospitalization/ER, 66.3% lower, RR 0.34, p = 0.01, treatment 7 of 88 (8.0%), control 21 of 90 (23.3%), NNT 6.5, odds ratio converted to relative risk, day 29.

risk of progression, 89.8% lower, RR 0.10, p = 0.009, treatment 1 of 88 (1.1%), control 10 of 90 (11.1%), NNT 10, ER visit, day 29.

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

1. Liu et al., Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2, bioRxiv, doi:10.1101/2021.12.14.472719.biorxiv.org, doi.org.

2. Sheward et al., Variable loss of antibody potency against SARS-CoV-2 B.1.1.529 (Omicron), bioRxiv, doi:10.1101/2021.12.19.473354.biorxiv.org, doi.org.

3. VanBlargan et al., An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies, bioRxiv, doi:10.1101/2021.12.15.472828.biorxiv.org, doi.org.

4. Haars et al., Prevalence of SARS-CoV-2 Omicron Sublineages and Spike Protein Mutations Conferring Resistance against Monoclonal Antibodies in a Swedish Cohort during 2022–2023, Microorganisms, doi:10.3390/microorganisms11102417.mdpi.com, doi.org.

5. Pochtovyi et al., In Vitro Efficacy of Antivirals and Monoclonal Antibodies against SARS-CoV-2 Omicron Lineages XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1, Vaccines, doi:10.3390/vaccines11101533.mdpi.com, doi.org.

6. Zhou et al., SARS-CoV-2 Omicron BA.2 Variant Evades Neutralization by Therapeutic Monoclonal Antibodies, bioRxiv, doi:10.1101/2022.02.15.480166.biorxiv.org, doi.org.

7. Uraki et al., Antiviral efficacy against and replicative fitness of an XBB.1.9.1 clinical isolate, iScience, doi:10.1016/j.isci.2023.108147.sciencedirect.com, doi.org.

Piccicacco et al., 1 Aug 2022, retrospective, USA, peer-reviewed, 7 authors, study period 27 December, 2021 - 4 February, 2022, average treatment delay 4.4 days. Contact: npiccicacco@tgh.org.

This Paper Sotrovimab 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

Agarwal, Rochwerg, Lamontagne, A living WHO guideline on drugs for covid-19, BMJ, doi:10.1136/bmj.m3379

Andrews, Stowe, Kirsebom, Covid-19 vaccine effectiveness against the Omicron (B.1.1.529) variant, N Engl J Med, doi:10.1056/NEJMoa2119451

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

Gupta, Gonzalez-Rojas, Juarez, Effect of sotrovimab on hospitalization or death among high-risk patients with mild to moderate COVID-19: a randomized clinical trial, JAMA, doi:10.1001/jama.2022.2832

Hui, Ho, Cheung, SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo, Nature, doi:10.1038/s41586-022-04479-6

Iuliano, Brunkard, Boehmer, Trends in disease severity and health care utilization during the early Omicron variant period compared with previous SARS-CoV-2 high transmission periods -United States, December 2020-January 2022, MMWR Morb Mortal Wkly Rep, doi:10.15585/mmwr.mm7104e4

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

Yek, Warner, Wiltz, Risk factors for severe COVID-19 outcomes among persons aged ≥18 years who completed a primary COVID-19 vaccination series -465 health care facilities, United States, MMWR Morb Mortal Wkly Rep, doi:10.15585/mmwr.mm7101a4

Zhu, Zhang, A novel coronavirus from patients with pneumonia in China, 2019, N Engl J Med, doi:10.1056/NEJMoa2001017

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