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Real-world effectiveness of nirmatrelvir/ritonavir against COVID-19 hospitalisations and severe COVID-19 in community-dwelling elderly Singaporeans during Omicron BA.2, BA.4/5 and XBB transmission

Wee et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2023.06.016
Jun 2023  
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Severe case 14% Improvement Relative Risk Hospitalization 35% Paxlovid for COVID-19  Wee et al.  EARLY TREATMENT Is early treatment with paxlovid beneficial for COVID-19? Retrospective 143,698 patients in Singapore (Mar - Dec 2022) Lower hospitalization with paxlovid (p=0.0015) c19early.org Wee et al., Clinical Microbiology and .., Jun 2023 Favorspaxlovid Favorscontrol 0 0.5 1 1.5 2+
Retrospective 3,959 paxlovid patients and 139,379 untreated controls, showing lower hospitalization with treatment. Contraindicted patients were excluded.
Confounding by treatment propensity. This study analyzes a population where only a fraction of eligible patients received the treatment. Patients receiving treatment may be more likely to follow other recommendations, more likely to receive additional care, and more likely to use additional treatments that are not tracked in the data (e.g., nasal/oral hygiene1,2, vitamin D3, etc.) — either because the physician recommending paxlovid also recommended them, or because the patient seeking out paxlovid is more likely to be familiar with the efficacy of additional treatments and more likely to take the time to use them. Malden et al. confirm significant bias in the use of paxlovid, showing that treated patients are more likely to be from affluent neighborhoods, be more health-conscious, and have better access to care. Therefore, these kind of studies may overestimate the efficacy of treatments.
Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid5. Retrospective studies that do not exclude contraindicated patients may significantly overestimate efficacy.
Black box warning. The FDA notes that "severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with paxlovid"6.
Use may promote the emergence of variants that weaken host immunity and potentially contribute to long COVID7.
Kamo et al. show significantly increased risk of acute kidney injury. Resistant variants are likely9,10.
risk of severe case, 14.0% lower, OR 0.86, p = 0.63, treatment 3,959, control 139,739, adjusted per study, multivariable, RR approximated with OR.
risk of hospitalization, 35.0% lower, OR 0.65, p = 0.002, treatment 3,959, control 139,739, adjusted per study, multivariable, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Wee et al., 17 Jun 2023, retrospective, Singapore, peer-reviewed, 11 authors, study period 18 March, 2022 - 31 December, 2022. Contact: ian.wee.l.e@singhealth.com.sg.
This PaperPaxlovidAll
Real-world effectiveness of nirmatrelvir/ritonavir against COVID-19 hospitalisations and severe COVID-19 in community-dwelling elderly Singaporeans during Omicron BA.2, BA.4/5 and XBB transmission
Liang En Wee, An Ting Tay, Calvin Chiew, Barnaby Edward Young, Betty Wong, Ruth Lim, Ching Li Lee, Joyce Tan, Shawn Vasoo, David Chien Lye, Kelvin Bryan Tan
Clinical Microbiology and Infection, doi:10.1016/j.cmi.2023.06.016
Real-world effectiveness of nirmatrelvir/ritonavir against COVID-19 hospitalisations and severe COVID-19 in community-dwelling elderly Singaporeans during Omicron BA.2, BA.4/5 and XBB transmission
Declarations Declaration of interests The authors report no conflicts of interest. Contribution statement LEW contributed to literature search and writing of the manuscript. ATT, CC, BEY, BW, RL, CLL, JT, SV, DCL and KBT contributed to critical review and editing of the manuscript. DCL and KBT provided supervision. KBT, ATT contributed to study design, data collection, and data analysis. All authors had full access to all the data in the study and take responsibility for the decision to submit for publication. KBT and ATT directly accessed and verified the underlying data reported in the manuscript. J o u r n a l P r e -p r o o f
References
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Sackett, Deeks, Altman, Down with odds ratios! Evidence Based Medicine
Savinkina, Paltiel, Ross, Gonsalves, Population-Level Strategies for Nirmatrelvir/Ritonavir Prescribing-A Cost-effectiveness Analysis. Open Forum Infect Dis, doi:10.1093/ofid/ofac637
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Tan, Lam, Matchar, Zee, Wong, Singapore's health-care system: key features, challenges, and shifts, Lancet, doi:10.1016/S0140-6736(21)00252-X
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Wai, Chan, Cheung, Wang, Chan et al., Association of Molnupiravir and Nirmatrelvir-Ritonavir with preventable mortality, hospital admissions and related avoidable healthcare system cost among high-risk patients with mild to moderate COVID-19. Lancet Reg Health West Pac, doi:10.1016/j.lanwpc.2022.100602
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Yip, Lui, Lai, Wong, Tse et al., Impact of the use of oral antiviral agents on the risk of hospitalization in community COVID-19 patients, Clin Infect Dis, doi:10.1093/cid/ciac687
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