Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data

Stella G Muthuri; Sudhir Venkatesan; Puja R Myles; Jo Leonardi-Bee; Tarig S A Al Khuwaitir; Adbullah Al Mamun; Ashish P Anovadiya; Eduardo Azziz-Baumgartner; Clarisa Báez; Matteo Bassetti; Bojana Beovic; Barbara Bertisch; Isabelle Bonmarin; Robert Booy; Victor H Borja-Aburto; Heinz Burgmann; Bin Cao; Jordi Carratala; Justin T Denholm; Samuel R Dominguez; Pericles A D Duarte; Gal Dubnov-Raz; Marcela Echavarria; Sergio Fanella; Zhancheng Gao; Patrick Gérardin; Maddalena Giannella; Sophie Gubbels; Jethro Herberg; Anjarath L Higuera Iglesias; Peter H Hoger; Xiaoyun Hu; Quazi T Islam; Mirela F Jiménez; Amr Kandeel; Gerben Keijzers; Hossein Khalili; Marian Knight; Koichiro Kudo; Gabriela Kusznierz; Ilija Kuzman; Arthur M C Kwan; Idriss Lahlou Amine; Eduard Langenegger; Kamran B Lankarani; Yee-Sin Leo; Pei Liu; Dhruv Parekh; Anna C Seale; PRIDE Consortium Investigators; Fang Gao Smith

doi:10.1016/S2213-2600(14)70041-4

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data

Stella G Muthuri, Sudhir Venkatesan, Puja R Myles, Jo Leonardi-Bee, Tarig S A Al Khuwaitir, Adbullah Al Mamun, Ashish P Anovadiya, Eduardo Azziz-Baumgartner, Clarisa Báez, Matteo Bassetti, Bojana Beovic, Barbara Bertisch, Isabelle Bonmarin, Robert Booy, Victor H Borja-Aburto, Heinz Burgmann, Bin Cao, Jordi Carratala, Justin T Denholm, Samuel R DominguezPericles A D Duarte, Gal Dubnov-Raz, Marcela Echavarria, Sergio Fanella, Zhancheng Gao, Patrick Gérardin, Maddalena Giannella, Sophie Gubbels, Jethro Herberg, Anjarath L Higuera Iglesias, Peter H Hoger, Xiaoyun Hu, Quazi T Islam, Mirela F Jiménez, Amr Kandeel, Gerben Keijzers, Hossein Khalili, Marian Knight, Koichiro Kudo, Gabriela Kusznierz, Ilija Kuzman, Arthur M C Kwan, Idriss Lahlou Amine, Eduard Langenegger, Kamran B Lankarani, Yee-Sin Leo, Pei Liu, Dhruv Parekh, Anna C Seale, PRIDE Consortium Investigators, Fang Gao Smith

Research output: Contribution to journal › Article › peer-review

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Abstract

BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection.

METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling.

FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each day's delay).

INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection.

FUNDING: F Hoffmann-La Roche.

Original language	English
Pages (from-to)	395-404
Number of pages	10
Journal	The Lancet Respiratory Medicine
Volume	2
Issue number	5
DOIs	https://doi.org/10.1016/S2213-2600(14)70041-4
Publication status	Published - May 2014

Bibliographical note

Keywords

Adolescent
Adult
Antiviral Agents
Child
Enzyme Inhibitors
Female
Hospitalization
Humans
Influenza A Virus, H1N1 Subtype
Influenza, Human
Male
Middle Aged
Neuraminidase
Oseltamivir
Pandemics
Proportional Hazards Models
Treatment Outcome
Young Adult
Zanamivir

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10.1016/S2213-2600(14)70041-4

Cite this

Muthuri, S. G., Venkatesan, S., Myles, P. R., Leonardi-Bee, J., Al Khuwaitir, T. S. A., Al Mamun, A., Anovadiya, A. P., Azziz-Baumgartner, E., Báez, C., Bassetti, M., Beovic, B., Bertisch, B., Bonmarin, I., Booy, R., Borja-Aburto, V. H., Burgmann, H., Cao, B., Carratala, J., Denholm, J. T., ... Gao Smith, F. (2014). Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. The Lancet Respiratory Medicine, 2(5), 395-404. https://doi.org/10.1016/S2213-2600(14)70041-4

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title = "Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data",

abstract = "BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection.METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling.FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each day's delay).INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection.FUNDING: F Hoffmann-La Roche.",

keywords = "Adolescent, Adult, Antiviral Agents, Child, Enzyme Inhibitors, Female, Hospitalization, Humans, Influenza A Virus, H1N1 Subtype, Influenza, Human, Male, Middle Aged, Neuraminidase, Oseltamivir, Pandemics, Proportional Hazards Models, Treatment Outcome, Young Adult, Zanamivir",

author = "Muthuri, {Stella G} and Sudhir Venkatesan and Myles, {Puja R} and Jo Leonardi-Bee and {Al Khuwaitir}, {Tarig S A} and {Al Mamun}, Adbullah and Anovadiya, {Ashish P} and Eduardo Azziz-Baumgartner and Clarisa B{\'a}ez and Matteo Bassetti and Bojana Beovic and Barbara Bertisch and Isabelle Bonmarin and Robert Booy and Borja-Aburto, {Victor H} and Heinz Burgmann and Bin Cao and Jordi Carratala and Denholm, {Justin T} and Dominguez, {Samuel R} and Duarte, {Pericles A D} and Gal Dubnov-Raz and Marcela Echavarria and Sergio Fanella and Zhancheng Gao and Patrick G{\'e}rardin and Maddalena Giannella and Sophie Gubbels and Jethro Herberg and Iglesias, {Anjarath L Higuera} and Hoger, {Peter H} and Xiaoyun Hu and Islam, {Quazi T} and Jim{\'e}nez, {Mirela F} and Amr Kandeel and Gerben Keijzers and Hossein Khalili and Marian Knight and Koichiro Kudo and Gabriela Kusznierz and Ilija Kuzman and Kwan, {Arthur M C} and Amine, {Idriss Lahlou} and Eduard Langenegger and Lankarani, {Kamran B} and Yee-Sin Leo and Pei Liu and Dhruv Parekh and Seale, {Anna C} and {PRIDE Consortium Investigators} and {Gao Smith}, Fang",

year = "2014",

month = may,

doi = "10.1016/S2213-2600(14)70041-4",

language = "English",

volume = "2",

pages = "395--404",

journal = "The Lancet Respiratory Medicine",

issn = "2213-2600",

publisher = "Elsevier",

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Muthuri, SG, Venkatesan, S, Myles, PR, Leonardi-Bee, J, Al Khuwaitir, TSA, Al Mamun, A, Anovadiya, AP, Azziz-Baumgartner, E, Báez, C, Bassetti, M, Beovic, B, Bertisch, B, Bonmarin, I, Booy, R, Borja-Aburto, VH, Burgmann, H, Cao, B, Carratala, J, Denholm, JT, Dominguez, SR, Duarte, PAD, Dubnov-Raz, G, Echavarria, M, Fanella, S, Gao, Z, Gérardin, P, Giannella, M, Gubbels, S, Herberg, J, Iglesias, ALH, Hoger, PH, Hu, X, Islam, QT, Jiménez, MF, Kandeel, A, Keijzers, G, Khalili, H, Knight, M, Kudo, K, Kusznierz, G, Kuzman, I, Kwan, AMC, Amine, IL, Langenegger, E, Lankarani, KB, Leo, Y-S, Liu, P, Parekh, D, Seale, AC, PRIDE Consortium Investigators & Gao Smith, F 2014, 'Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data', The Lancet Respiratory Medicine, vol. 2, no. 5, pp. 395-404. https://doi.org/10.1016/S2213-2600(14)70041-4

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. / Muthuri, Stella G; Venkatesan, Sudhir; Myles, Puja R et al.
In: The Lancet Respiratory Medicine, Vol. 2, No. 5, 05.2014, p. 395-404.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection

T2 - a meta-analysis of individual participant data

AU - Muthuri, Stella G

AU - Venkatesan, Sudhir

AU - Myles, Puja R

AU - Leonardi-Bee, Jo

AU - Al Khuwaitir, Tarig S A

AU - Al Mamun, Adbullah

AU - Anovadiya, Ashish P

AU - Azziz-Baumgartner, Eduardo

AU - Báez, Clarisa

AU - Bassetti, Matteo

AU - Beovic, Bojana

AU - Bertisch, Barbara

AU - Bonmarin, Isabelle

AU - Booy, Robert

AU - Borja-Aburto, Victor H

AU - Burgmann, Heinz

AU - Cao, Bin

AU - Carratala, Jordi

AU - Denholm, Justin T

AU - Dominguez, Samuel R

AU - Duarte, Pericles A D

AU - Dubnov-Raz, Gal

AU - Echavarria, Marcela

AU - Fanella, Sergio

AU - Gao, Zhancheng

AU - Gérardin, Patrick

AU - Giannella, Maddalena

AU - Gubbels, Sophie

AU - Herberg, Jethro

AU - Iglesias, Anjarath L Higuera

AU - Hoger, Peter H

AU - Hu, Xiaoyun

AU - Islam, Quazi T

AU - Jiménez, Mirela F

AU - Kandeel, Amr

AU - Keijzers, Gerben

AU - Khalili, Hossein

AU - Knight, Marian

AU - Kudo, Koichiro

AU - Kusznierz, Gabriela

AU - Kuzman, Ilija

AU - Kwan, Arthur M C

AU - Amine, Idriss Lahlou

AU - Langenegger, Eduard

AU - Lankarani, Kamran B

AU - Leo, Yee-Sin

AU - Liu, Pei

AU - Parekh, Dhruv

AU - Seale, Anna C

AU - PRIDE Consortium Investigators

AU - Gao Smith, Fang

PY - 2014/5

Y1 - 2014/5

N2 - BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection.METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling.FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each day's delay).INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection.FUNDING: F Hoffmann-La Roche.

AB - BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection.METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling.FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each day's delay).INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection.FUNDING: F Hoffmann-La Roche.

KW - Adolescent

KW - Adult

KW - Antiviral Agents

KW - Child

KW - Enzyme Inhibitors

KW - Female

KW - Hospitalization

KW - Humans

KW - Influenza A Virus, H1N1 Subtype

KW - Influenza, Human

KW - Male

KW - Middle Aged

KW - Neuraminidase

KW - Oseltamivir

KW - Pandemics

KW - Proportional Hazards Models

KW - Treatment Outcome

KW - Young Adult

KW - Zanamivir

U2 - 10.1016/S2213-2600(14)70041-4

DO - 10.1016/S2213-2600(14)70041-4

M3 - Article

C2 - 24815805

SN - 2213-2600

VL - 2

SP - 395

EP - 404

JO - The Lancet Respiratory Medicine

JF - The Lancet Respiratory Medicine

IS - 5

ER -

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data

Abstract

Bibliographical note

Keywords

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