Efficacy and safety of current medications for treating severe and non-severe COVID-19 patients : an updated network meta-analysis of randomized placebo-controlled trials

BACKGROUND: Many recent studies have investigated the role of drug interventions for coronavirus disease 2019 (COVID-19) infection. However, an important question has been raised about how to select the effective and secure medications for COVID-19 patients. The aim of this analysis was to assess the efficacy and safety of the various medications available for severe and non-severe COVID-19 patients based on randomized placebo-controlled trials (RPCTs).

METHODS: We did an updated network meta-analysis. We searched the databases from inception until July 31, 2021, with no language restrictions. We included RPCTs comparing 49 medications and placebo in the treatment of severe and non-severe patients (aged 18 years or older) with COVID-19 infection. We extracted data on the trial and patient characteristics, and the following primary outcomes: all-cause mortality, the ratios of virological cure, and treatment-emergent adverse events. Odds ratio (OR) and their 95% confidence interval (CI) were used as effect estimates.

RESULTS: From 3,869 publications, we included 61 articles related to 73 RPCTs (57 in non-severe COVID-19 patients and 16 in severe COVID-19 patients), comprising 20,680 patients. The mean sample size was 160 (interquartile range 96-393) in this study. The median duration of follow-up drugs intervention was 28 days (interquartile range 21-30). For increase in virological cure, we only found that proxalutamide (OR 9.16, 95% CI 3.15-18.30), ivermectin (OR 6.33, 95% CI 1.22-32.86), and low dosage bamlanivimab (OR 5.29, 95% CI 1.12-24.99) seemed to be associated with non-severe COVID-19 patients when compared with placebo, in which proxalutamide seemed to be better than low dosage bamlanivimab (OR 5.69, 95% CI 2.43-17.65). For decrease in all-cause mortality, we found that proxalutamide (OR 0.13, 95% CI 0.09-0.19), imatinib (OR 0.49, 95% CI 0.25-0.96), and baricitinib (OR 0.58, 95% CI 0.42-0.82) seemed to be associated with non-severe COVID-19 patients; however, we only found that immunoglobulin gamma (OR 0.27, 95% CI 0.08-0.89) was related to severe COVID-19 patients when compared with placebo. For change in treatment-emergent adverse events, we only found that sotrovimab (OR 0.21, 95% CI 0.13-0.34) was associated with non-severe COVID-19 patients; however, we did not find any medications that presented a statistical difference when compared with placebo among severe COVID-19 patients.

CONCLUSION: We conclude that marked variations exist in the efficacy and safety of medications between severe and non-severe patients with COVID-19. It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clinical decisions to use preferentially medications should carefully consider the risk-benefit profile based on efficacy and safety of all active interventions in patients with COVID-19 at different levels of infection.

Medienart:	E-Artikel

Erscheinungsjahr:	2021
Erschienen:	2021

Enthalten in:	Zur Gesamtaufnahme - volume:13
Enthalten in:	Aging - 13(2021), 18 vom: 16. Sept., Seite 21866-21902

Sprache:	Englisch

Beteiligte Personen:	Cheng, Qinglin [VerfasserIn] Chen, Junfang [VerfasserIn] Jia, Qingjun [VerfasserIn] Fang, Zijian [VerfasserIn] Zhao, Gang [VerfasserIn]

Links:	Volltext

Themen:

1MTK0BPN8V 45I6OFJ8QH 8A1O1M485B Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Azetidines Bamlanivimab Baricitinib COVID-19 Efficacy ISP4442I3Y Imatinib Mesylate Immunologic Factors Journal Article Meta-Analysis Network meta-analysis Oxazoles Proxalutamide Purines Pyrazoles QX6O64GP40 Randomized placebo-controlled trials Research Support, Non-U.S. Gov't Safety Sotrovimab Sulfonamides Systematic Review Thiohydantoins

Anmerkungen:	Date Completed 15.10.2021 Date Revised 03.11.2023 published: Print-Electronic Citation Status MEDLINE

doi:	10.18632/aging.203522

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	NLM330733036