Comparison of Antiviral Agents for Seasonal Influenza Outcomes in Healthy Adults and Children: A Systematic Review and Network Meta-analysis
Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2; however, questions remain about which treatment is associated with the best outcomes and fewest adverse events. To compare the effic...
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| creator | Liu, Jen-Wei Lin, Shen-Hua Wang, Lin-Chien Chiu, Hsiao-Yean Lee, Jen-Ai |
| description | Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2; however, questions remain about which treatment is associated with the best outcomes and fewest adverse events.
To compare the efficacy and safety of neuraminidase inhibitors and the endonuclease inhibitor for the treatment of seasonal influenza among healthy adults and children.
Medline, Embase, and the Cochrane Register of Clinical Trials were searched from inception to January 2020 (the last search was updated in October 2020).
Included studies were randomized clinical trials conducted among patients of all ages with influenza treated with neuraminidase inhibitors (ie, oseltamivir, peramivir, zanamivir, or laninamivir) or an endonuclease inhibitor (ie, baloxavir) compared with other active agents or placebo.
Two investigators identified studies and independently abstracted data. Frequentist network meta-analyses were performed; relative ranking of agents was conducted using P-score probabilities. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. Data were analyzed in October 2020.
The time to alleviation of influenza symptoms (TTAS), complications of influenza, and adverse events (total adverse events, nausea, and vomiting).
A total of 26 trials were identified that investigated antiviral drugs at high or low doses; these trials included 11 897 participants, among whom 6294 (52.9%) were men and the mean (SD) age was 32.5 (16.9) years. Of all treatments comparing with placebo in efficacy outcomes, high-quality evidence indicated that zanamivir was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80) based on moderate-quality evidence. In safety outcomes, baloxavir was associated with the lowest risk of total adverse events (RR, 0.84; 95% CI, 0.74-0.96) compared with placebo based on moderate-quality evidence. There was no strong evidence of associations with risk of nausea or vomiting among all comparisons, except for 75 mg oseltamivir, which was associated with greater occurrence of nausea (RR, 1.82; 95% CI, 1.38-2.41) and vomiting (RR, 1.88; 95% CI, 1.47-2.41).
In this systematic review and network meta-analysis, all 4 antiviral agents assessed were associated with sho |
| doi_str_mv | 10.1001/jamanetworkopen.2021.19151 |
| format | Article |
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To compare the efficacy and safety of neuraminidase inhibitors and the endonuclease inhibitor for the treatment of seasonal influenza among healthy adults and children.
Medline, Embase, and the Cochrane Register of Clinical Trials were searched from inception to January 2020 (the last search was updated in October 2020).
Included studies were randomized clinical trials conducted among patients of all ages with influenza treated with neuraminidase inhibitors (ie, oseltamivir, peramivir, zanamivir, or laninamivir) or an endonuclease inhibitor (ie, baloxavir) compared with other active agents or placebo.
Two investigators identified studies and independently abstracted data. Frequentist network meta-analyses were performed; relative ranking of agents was conducted using P-score probabilities. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. Data were analyzed in October 2020.
The time to alleviation of influenza symptoms (TTAS), complications of influenza, and adverse events (total adverse events, nausea, and vomiting).
A total of 26 trials were identified that investigated antiviral drugs at high or low doses; these trials included 11 897 participants, among whom 6294 (52.9%) were men and the mean (SD) age was 32.5 (16.9) years. Of all treatments comparing with placebo in efficacy outcomes, high-quality evidence indicated that zanamivir was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80) based on moderate-quality evidence. In safety outcomes, baloxavir was associated with the lowest risk of total adverse events (RR, 0.84; 95% CI, 0.74-0.96) compared with placebo based on moderate-quality evidence. There was no strong evidence of associations with risk of nausea or vomiting among all comparisons, except for 75 mg oseltamivir, which was associated with greater occurrence of nausea (RR, 1.82; 95% CI, 1.38-2.41) and vomiting (RR, 1.88; 95% CI, 1.47-2.41).
In this systematic review and network meta-analysis, all 4 antiviral agents assessed were associated with shortening TTAS; zanamivir was associated with the shortest TTAS, and baloxavir was associated with reduced rate of influenza-related complications.</description><identifier>ISSN: 2574-3805</identifier><identifier>EISSN: 2574-3805</identifier><identifier>DOI: 10.1001/jamanetworkopen.2021.19151</identifier><identifier>PMID: 34387680</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Adolescent ; Adult ; Antiviral Agents - therapeutic use ; Antiviral drugs ; Child ; Clinical trials ; Dibenzothiepins - therapeutic use ; Endonucleases - antagonists & inhibitors ; Enzyme Inhibitors - therapeutic use ; Female ; Humans ; Infectious Diseases ; Influenza ; Influenza A virus - drug effects ; Influenza, Human - drug therapy ; Influenza, Human - virology ; Male ; Meta-analysis ; Middle Aged ; Morpholines - therapeutic use ; Nausea ; Network Meta-Analysis ; Neuraminidase - antagonists & inhibitors ; Online Only ; Original Investigation ; Pyridones - therapeutic use ; Randomized Controlled Trials as Topic ; Seasons ; Severe acute respiratory syndrome coronavirus 2 ; Systematic review ; Triazines - therapeutic use ; Vomiting ; Young Adult ; Zanamivir - therapeutic use</subject><ispartof>JAMA network open, 2021-08, Vol.4 (8), p.e2119151-e2119151</ispartof><rights>2021. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Copyright 2021 Liu JW et al. .</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a364t-8b46e4d932c9d8289d665dab988fa3311bb61ba994d82178ce99c6b579c04ebe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,860,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34387680$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Jen-Wei</creatorcontrib><creatorcontrib>Lin, Shen-Hua</creatorcontrib><creatorcontrib>Wang, Lin-Chien</creatorcontrib><creatorcontrib>Chiu, Hsiao-Yean</creatorcontrib><creatorcontrib>Lee, Jen-Ai</creatorcontrib><title>Comparison of Antiviral Agents for Seasonal Influenza Outcomes in Healthy Adults and Children: A Systematic Review and Network Meta-analysis</title><title>JAMA network open</title><addtitle>JAMA Netw Open</addtitle><description>Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2; however, questions remain about which treatment is associated with the best outcomes and fewest adverse events.
To compare the efficacy and safety of neuraminidase inhibitors and the endonuclease inhibitor for the treatment of seasonal influenza among healthy adults and children.
Medline, Embase, and the Cochrane Register of Clinical Trials were searched from inception to January 2020 (the last search was updated in October 2020).
Included studies were randomized clinical trials conducted among patients of all ages with influenza treated with neuraminidase inhibitors (ie, oseltamivir, peramivir, zanamivir, or laninamivir) or an endonuclease inhibitor (ie, baloxavir) compared with other active agents or placebo.
Two investigators identified studies and independently abstracted data. Frequentist network meta-analyses were performed; relative ranking of agents was conducted using P-score probabilities. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. Data were analyzed in October 2020.
The time to alleviation of influenza symptoms (TTAS), complications of influenza, and adverse events (total adverse events, nausea, and vomiting).
A total of 26 trials were identified that investigated antiviral drugs at high or low doses; these trials included 11 897 participants, among whom 6294 (52.9%) were men and the mean (SD) age was 32.5 (16.9) years. Of all treatments comparing with placebo in efficacy outcomes, high-quality evidence indicated that zanamivir was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80) based on moderate-quality evidence. In safety outcomes, baloxavir was associated with the lowest risk of total adverse events (RR, 0.84; 95% CI, 0.74-0.96) compared with placebo based on moderate-quality evidence. There was no strong evidence of associations with risk of nausea or vomiting among all comparisons, except for 75 mg oseltamivir, which was associated with greater occurrence of nausea (RR, 1.82; 95% CI, 1.38-2.41) and vomiting (RR, 1.88; 95% CI, 1.47-2.41).
In this systematic review and network meta-analysis, all 4 antiviral agents assessed were associated with shortening TTAS; zanamivir was associated with the shortest TTAS, and baloxavir was associated with reduced rate of influenza-related complications.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Antiviral drugs</subject><subject>Child</subject><subject>Clinical trials</subject><subject>Dibenzothiepins - therapeutic use</subject><subject>Endonucleases - antagonists & inhibitors</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Female</subject><subject>Humans</subject><subject>Infectious Diseases</subject><subject>Influenza</subject><subject>Influenza A virus - drug effects</subject><subject>Influenza, Human - drug therapy</subject><subject>Influenza, Human - virology</subject><subject>Male</subject><subject>Meta-analysis</subject><subject>Middle Aged</subject><subject>Morpholines - therapeutic use</subject><subject>Nausea</subject><subject>Network Meta-Analysis</subject><subject>Neuraminidase - antagonists & inhibitors</subject><subject>Online Only</subject><subject>Original Investigation</subject><subject>Pyridones - therapeutic use</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Seasons</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Systematic review</subject><subject>Triazines - therapeutic use</subject><subject>Vomiting</subject><subject>Young Adult</subject><subject>Zanamivir - therapeutic use</subject><issn>2574-3805</issn><issn>2574-3805</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkcFu1DAYhCMEolXpKyALLlyy2LHj2D0gRSuglQqVKJwtx_nT9ZLYi-1stTxDH7put1SlJ1ueb0YeTVG8I3hBMCYf13rSDtK1D7_9BtyiwhVZEElq8qI4rOqGlVTg-uWT-0FxHOMaY1xhQiWvXxcHlFHRcIEPi5ulnzY62Ogd8gNqXbJbG_SI2itwKaLBB3QJOsv57cwN4wzur0YXczJ-goisQ6egx7Taobafx-zQrkfLlR37AO4EtehyFxNMOlmDfsDWwvU98X1fAX2DpEudw3fRxjfFq0GPEY4fzqPi15fPP5en5fnF17Nle15qylkqRcc4sF7SysheVEL2nNe97qQQg6aUkK7jpNNSsqySRhiQ0vCubqTBDDqgR8Wnfe5m7iboTW6aK6tNsJMOO-W1Vf8rzq7Uld8qQTmVROSADw8Bwf-ZISY12WhgHPM0fo6qqjlhkjBeZ_T9M3Tt55ALZ4rzRmBGCc_UyZ4ywccYYHj8DMHqbnf1bHd1t7u63z2b3z6t82j9tzK9BalXsU0</recordid><startdate>20210802</startdate><enddate>20210802</enddate><creator>Liu, Jen-Wei</creator><creator>Lin, Shen-Hua</creator><creator>Wang, Lin-Chien</creator><creator>Chiu, Hsiao-Yean</creator><creator>Lee, Jen-Ai</creator><general>American Medical Association</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210802</creationdate><title>Comparison of Antiviral Agents for Seasonal Influenza Outcomes in Healthy Adults and Children: A Systematic Review and Network Meta-analysis</title><author>Liu, Jen-Wei ; Lin, Shen-Hua ; Wang, Lin-Chien ; Chiu, Hsiao-Yean ; Lee, Jen-Ai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a364t-8b46e4d932c9d8289d665dab988fa3311bb61ba994d82178ce99c6b579c04ebe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Antiviral drugs</topic><topic>Child</topic><topic>Clinical trials</topic><topic>Dibenzothiepins - therapeutic use</topic><topic>Endonucleases - antagonists & inhibitors</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>Female</topic><topic>Humans</topic><topic>Infectious Diseases</topic><topic>Influenza</topic><topic>Influenza A virus - drug effects</topic><topic>Influenza, Human - drug therapy</topic><topic>Influenza, Human - virology</topic><topic>Male</topic><topic>Meta-analysis</topic><topic>Middle Aged</topic><topic>Morpholines - therapeutic use</topic><topic>Nausea</topic><topic>Network Meta-Analysis</topic><topic>Neuraminidase - antagonists & inhibitors</topic><topic>Online Only</topic><topic>Original Investigation</topic><topic>Pyridones - therapeutic use</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Seasons</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Systematic review</topic><topic>Triazines - therapeutic use</topic><topic>Vomiting</topic><topic>Young Adult</topic><topic>Zanamivir - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Jen-Wei</creatorcontrib><creatorcontrib>Lin, Shen-Hua</creatorcontrib><creatorcontrib>Wang, Lin-Chien</creatorcontrib><creatorcontrib>Chiu, Hsiao-Yean</creatorcontrib><creatorcontrib>Lee, Jen-Ai</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JAMA network open</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Jen-Wei</au><au>Lin, Shen-Hua</au><au>Wang, Lin-Chien</au><au>Chiu, Hsiao-Yean</au><au>Lee, Jen-Ai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of Antiviral Agents for Seasonal Influenza Outcomes in Healthy Adults and Children: A Systematic Review and Network Meta-analysis</atitle><jtitle>JAMA network open</jtitle><addtitle>JAMA Netw Open</addtitle><date>2021-08-02</date><risdate>2021</risdate><volume>4</volume><issue>8</issue><spage>e2119151</spage><epage>e2119151</epage><pages>e2119151-e2119151</pages><issn>2574-3805</issn><eissn>2574-3805</eissn><abstract>Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2; however, questions remain about which treatment is associated with the best outcomes and fewest adverse events.
To compare the efficacy and safety of neuraminidase inhibitors and the endonuclease inhibitor for the treatment of seasonal influenza among healthy adults and children.
Medline, Embase, and the Cochrane Register of Clinical Trials were searched from inception to January 2020 (the last search was updated in October 2020).
Included studies were randomized clinical trials conducted among patients of all ages with influenza treated with neuraminidase inhibitors (ie, oseltamivir, peramivir, zanamivir, or laninamivir) or an endonuclease inhibitor (ie, baloxavir) compared with other active agents or placebo.
Two investigators identified studies and independently abstracted data. Frequentist network meta-analyses were performed; relative ranking of agents was conducted using P-score probabilities. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. Data were analyzed in October 2020.
The time to alleviation of influenza symptoms (TTAS), complications of influenza, and adverse events (total adverse events, nausea, and vomiting).
A total of 26 trials were identified that investigated antiviral drugs at high or low doses; these trials included 11 897 participants, among whom 6294 (52.9%) were men and the mean (SD) age was 32.5 (16.9) years. Of all treatments comparing with placebo in efficacy outcomes, high-quality evidence indicated that zanamivir was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80) based on moderate-quality evidence. In safety outcomes, baloxavir was associated with the lowest risk of total adverse events (RR, 0.84; 95% CI, 0.74-0.96) compared with placebo based on moderate-quality evidence. There was no strong evidence of associations with risk of nausea or vomiting among all comparisons, except for 75 mg oseltamivir, which was associated with greater occurrence of nausea (RR, 1.82; 95% CI, 1.38-2.41) and vomiting (RR, 1.88; 95% CI, 1.47-2.41).
In this systematic review and network meta-analysis, all 4 antiviral agents assessed were associated with shortening TTAS; zanamivir was associated with the shortest TTAS, and baloxavir was associated with reduced rate of influenza-related complications.</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>34387680</pmid><doi>10.1001/jamanetworkopen.2021.19151</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Antiviral Agents - therapeutic use Antiviral drugs Child Clinical trials Dibenzothiepins - therapeutic use Endonucleases - antagonists & inhibitors Enzyme Inhibitors - therapeutic use Female Humans Infectious Diseases Influenza Influenza A virus - drug effects Influenza, Human - drug therapy Influenza, Human - virology Male Meta-analysis Middle Aged Morpholines - therapeutic use Nausea Network Meta-Analysis Neuraminidase - antagonists & inhibitors Online Only Original Investigation Pyridones - therapeutic use Randomized Controlled Trials as Topic Seasons Severe acute respiratory syndrome coronavirus 2 Systematic review Triazines - therapeutic use Vomiting Young Adult Zanamivir - therapeutic use |
| title | Comparison of Antiviral Agents for Seasonal Influenza Outcomes in Healthy Adults and Children: A Systematic Review and Network Meta-analysis |
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