Efficacy of remdesivir in hospitalized nonsevere COVID-19 patients in Japan: A large observational study using the COVID-19 Registry Japan

Tsuzuki et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2022.02.039, Mar 2021 (preprint)

https://c19early.org/tsuzuki.html

Retrospective database analysis of 12,487 hospitalized patients in Japan, showing lower risk of oxygen requirement, but no significant difference in mortality or ventilation/ECMO.

Gérard, Zhou, Wu, Kamo, Choi, Kim show increased risk of acute kidney injury with remdesivir. Leo, Briciu, Muntean, Petrov show increased risk of liver injury with remdesivir.

Standard of Care (SOC) for COVID-19 in the study country, Japan, is very poor with very low average efficacy for approved treatments11. Only expensive, high-profit treatments were approved. Low-cost treatments were excluded, reducing the probability of treatment—especially early—due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.

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risk of death, 4.0% higher, HR 1.04, p = 0.21, treatment 69 of 824 (8.4%), control 285 of 11,663 (2.4%), adjusted per study, day 30.

risk of mechanical ventilation or ECMO, 1.7% lower, HR 0.98, p = 0.68, treatment 48 of 824 (5.8%), control 98 of 11,663 (0.8%), adjusted per study.

risk of progression, 15.0% lower, HR 0.85, p = 0.68, treatment 559 of 824 (67.8%), control 1,784 of 11,663 (15.3%), adjusted per study.

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. Leo et al., Hepatocellular liver injury in hospitalized patients affected by COVID-19: Presence of different risk factors at different time points, Digestive and Liver Disease, doi:10.1016/j.dld.2021.12.014.sciencedirect.com, doi.org.

8. Briciu et al., Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting, Pathogens, doi:10.3390/pathogens12121453.mdpi.com, doi.org.

9. Muntean et al., Effects of COVID-19 on the Liver and Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta and Non-Delta Variants: An Analysis in a Single Centre, Pharmaceuticals, doi:10.3390/ph17010003.mdpi.com, doi.org.

10. Petrov et al., The Effect of Potentially Hepatotoxic Medicinal Products on Alanine Transaminase Levels in COVID-19 Patients: A Case–Control Study, Safety and Risk of Pharmacotherapy, doi:10.30895/2312-7821-2025-458.risksafety.ru, doi.org.

11. c19early.org, c19early.org/soc/japan.html.c19early.org/soc/japan.html.

Tsuzuki et al., 10 Mar 2021, retrospective, Japan, peer-reviewed, 21 authors, average treatment delay 6.0 days.

This Paper Remdesivir All

Effectiveness of remdesivir in hospitalized nonsevere patients with COVID-19 in Japan: A large observational study using the COVID-19 Registry Japan

Shinya Tsuzuki, Kayoko Hayakawa, Yukari Uemura, Tomohiro Shinozaki, Nobuaki Matsunaga, Mari Terada, Setsuko Suzuki, Yusuke Asai, Koji Kitajima, Sho Saito, Gen Yamada, Taro Shibata, Masashi Kondo, Kazuo Izumi, Masayuki Hojo, Tetsuya Mizoue, Kazuhisa Yokota, Fukumi Nakamura-Uchiyama, Fumitake Saito, Wataru Sugiura, Norio Ohmagari

International Journal of Infectious Diseases, doi:10.1016/j.ijid.2022.02.039

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Ethics This study was approved by the NCGM ethics review (NCGM-G-003494-0). Information regarding opting out of our study is available on the registry website. Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

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Late treatment
is less effective

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