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. 2024 Aug;13(8):1821-1833.
doi: 10.1007/s40121-024-01010-4. Epub 2024 Jun 28.

Real-World Effectiveness of Ensitrelvir in Reducing Severe Outcomes in Outpatients at High Risk for COVID-19

Takahiro Takazono  1 , Satoki Fujita  2 , Takuji Komeda  3 , Shogo Miyazawa  3 , Yuki Yoshida  3 , Yoshitake Kitanishi  3 , Masahiro Kinoshita  4 , Satoshi Kojima  4 , Huilian Shen  4 , Takeki Uehara  5 , Naoki Hosogaya  1 , Naoki Iwanaga  1 , Hiroshi Mukae  1   6
Affiliations

Real-World Effectiveness of Ensitrelvir in Reducing Severe Outcomes in Outpatients at High Risk for COVID-19

Takahiro Takazono et al. Infect Dis Ther. 2024 Aug.

Abstract

Introduction: This study aimed to evaluate the effectiveness of ensitrelvir, an oral antiviral, in reducing hospitalization risk in outpatients at high-risk for severe COVID-19 during the Omicron era.

Methods: This was a retrospective study using a large Japanese health insurance claims database. It included high-risk outpatients for severe symptoms who received their first COVID-19 diagnosis between November 2022 and July 2023. The study included outpatients aged ≥ 18 years. The primary endpoint was all-cause hospitalization during the 4-week period from the date of outpatient diagnosis and medication, comparing the ensitrelvir group (n = 5177) and the no antiviral treatment group (n = 162,133). The risk ratio and risk difference were evaluated after adjusting patient background distribution by the inverse probability of treatment weight (IPTW) method. Secondary endpoints were incidence of respiratory and heart rate monitoring, oxygen therapy, ventilator use, intensive care admission, and all-cause death.

Results: The risk ratio for all-cause hospitalization between the ensitrelvir group (n = 167,385) and the no antiviral treatment group (n = 167,310) after IPTW adjustment was 0.629 [95% confidence interval (CI) 0.420, 0.943]. The risk difference was - 0.291 [95% CI - 0.494, - 0.088]. The incidence of both respiratory and heart rate monitoring and oxygen therapy was lower in the ensitrelvir group. Ventilator use, intensive care admission, and all-cause death were difficult to assess because of the limited events.

Conclusions: The incidence of all-cause hospitalization was significantly lower in the ensitrelvir group than in the no antiviral treatment group, suggesting ensitrelvir is an effective treatment in patients at risk of severe COVID-19.

Keywords: COVID-19; Ensitrelvir; Hospitalization; Japanese nationwide database.

Plain language summary

COVID-19 still poses a risk for patients with serious health conditions and weakened immune systems, who are more likely to develop severe illness. Several studies have indicated that some oral antiviral medications might be effective in preventing severe disease. This study aimed to evaluate if ensitrelvir, an oral antiviral medication, can help prevent hospitalization in outpatients who are at risk of developing severe symptoms from the Omicron variant of the SARS-CoV-2 virus. The hospitalization rates of patients who received ensitrelvir was compared with those who did not receive any antiviral treatment, using medical records from a large health insurance database in Japan focused on outpatients who were at risk of severe symptoms and were diagnosed with COVID-19 between November 2022 and July 2023. Respiratory and heart rate monitoring, oxygen therapy, ventilator use, intensive care admission, and all-cause death were also evaluated. The study found that patients who received ensitrelvir had a lower risk of being hospitalized compared to those who did not receive any antiviral treatment. The ensitrelvir group also had lower rates of respiratory and heart rate monitoring and oxygen therapy. However, it was challenging to assess the effects on ventilator use, intensive care admission, and all-cause death due to the small number of events in the population under evaluation. Based on these findings, ensitrelvir appears to be an effective treatment for reducing the risk of hospitalization in patients at risk of severe COVID-19.

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Conflict of interest statement

Satoki Fujita, Takuji Komeda, Shogo Miyazawa, Yuki Yoshida, Yoshitake Kitanishi, Masahiro Kinoshita, Satoshi Kojima, Huilian Shen, and Takeki Uehara are employees of Shionogi & Co., Ltd. and may hold stocks in the company. Takahiro Takazono has received personal fees from Shionogi & Co., Ltd., MSD K.K., Pfizer Japan Inc., Insmed GK., Asahi Kasei Pharma Corporation, and Kyorin Pharmaceutical Co., Ltd. Hiroshi Mukae has also received personal fees from AbbVie GK., Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AstraZeneca K.K., Bristol-Myers Squibb K.K., Eli Lilly Japan K.K., FUJIFILM Toyama Chemical Co., Ltd., Gilead Sciences Inc., Insmed GK., Janssen Pharmaceutical K.K., Kyorin Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nihon Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Pfizer Japan Inc., Sumitomo Pharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Taisho Pharma Co., Ltd., Teijin Healthcare Ltd., and Toa Shinyaku Co., Ltd., and grants from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., FUJIFILM Toyama Chemical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., Pfizer Japan Inc., Taiho Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Teijin Pharma Ltd., Toa Shinyaku Co., Ltd., and Torii Pharmaceutical Co., Ltd., outside the submitted work. Naoki Hosogaya and Naoki Iwanaga have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Flow chart of study population. COVID-19 coronavirus disease 2019
Fig. 2
Fig. 2
Incidence and risk of events in patients with risk factors in ensitrelvir treatment group and no antiviral treatment group. CI confidence interval, ICU intensive care unit, IPTW inverse probability of treatment weighting, RD risk difference, RR risk ratio
Fig. 3
Fig. 3
Adjusted cumulative incidence of all-cause hospitalization in high-risk patients in the ensitrelvir treatment group or the no antiviral treatment group
See this image and copyright information in PMC

References

    1. Manchanda V, Mitra S, Rafique I, et al. Is Omicron really mild?—comparative analysis of comorbidities and disease outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants. Indian J Med Microbiol. 2023;45: 100391. 10.1016/j.ijmmb.2023.100391 - DOI - PMC - PubMed
    1. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med. 2022;386(15):1397–408. 10.1056/NEJMoa2118542 - DOI - PMC - PubMed
    1. Jayk Bernal A, da Silva MMG, Musungaie DB, et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N Engl J Med. 2022;386(6):509–20. 10.1056/NEJMoa2116044 - DOI - PMC - PubMed
    1. Arbel R, Wolff Sagy Y, Hoshen M, et al. Nirmatrelvir use and severe Covid-19 outcomes during the Omicron surge. N Engl J Med. 2022;387(9):790–8. 10.1056/NEJMoa2204919 - DOI - PMC - PubMed
    1. Shah MM, Joyce B, Plumb ID, et al. Paxlovid associated with decreased hospitalization rate among adults with COVID-19–United States, April–September 2022. MMWR Morb Mortal Wkly Rep. 2022;71(48):1531–7. 10.15585/mmwr.mm7148e2 - DOI - PMC - PubMed

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