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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.; Leonardi-Bee, Jo; Al Khuwaitir, Tarig S.; Al Mamun, Abdullah; Anovadiya, Ashish P.; Azziz-Baumgartner, Eduardo; Báez, Clarisa; Bassetti, Matteo; Beovic, Bojana; Bertisch, Barbara; Bonmarin, Isabelle; Booy, Robert; Borja-Aburto, Victor H.; Burgmann, Heinz; Cao, Bin; Carratala, Jordi; Denholm, Justin T.; Dominguez, Samuel R.; Duarte, Pericles A.D.; Dubnov-Raz, Gal; Echavarria, Marcela; Fanella, Sergio; Gao, Zhancheng; Gérardin, Patrick; Gianella, Maddalena; Gubbels, Sophie; Herberg, Jethro; Iglesias, Anjarath L. Higuera; Hoger, Peter H.; Hu, Xiaoyun; Islam, Quazi T.; Jiménez, Mirela F.; Kandeel, Amr; Keijzers, Gerben; Khalili, Hossein; Knight, Marian; Kudo, Koichiro; Kusznierz, Gabriela; Kuzman, Iljia; Kwan, Arthur M.C.; Amine, Idriss Lahlou; Langenegger, Eduard; Lankarani, Kamran B,; Leo, Yee-Sin; Linko, Rita; Liu, Pei; Madanat, Faris; Mayo-Montero, Elga; McGeer, Allison; Memish, Ziad; Metan, Gokhan; Mickiene, Aukse; Mikić, Dragan; Mohn, Kristin G.; Moradi, Ahmadreza; Nymadawa, Pagbajabyn; Oliva, Maria E.; Oskan, Mehpare; Parekh, Dhruv; Paul, Mical; Polack, Fernando P.; Rath, Barbara A.; Rodríguez, Alejandro H.; Sarrouf, Elena B.; Seale, Anna C.; Sertogullarindan, Bunyamin; Siqueira, Marilda M.; Skręt-Magierło, Joanna; Stephan, Frank; Talarek, Ewa; Tang, Julian W.; To, Kelvin K.; Torres, Antoni; Törün, Selda H.; Tran, Dat; Uyeki, Timothy M.; Van Zwol, Annelies; Vaudry, Wendy; Vidmar, Tjasa; Yokota, Renata T.C.; Zarogoulidis, Paul; Nguyen-Van-Tam, Jonathan

Authors

Stella G. Muthuri stella.muthuri@gmail.com

Sudhir Venkatesan sudhir.venkatesan@nottingham.ac.uk

Puja R. Myles puja.myles@nottingham.ac.uk

JO LEONARDI-BEE jo.leonardi-bee@nottingham.ac.uk
Professor of Medical Statistics and Epidemiology

Tarig S. Al Khuwaitir

Abdullah 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 Gianella

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

Iljia Kuzman

Arthur M.C. Kwan

Idriss Lahlou Amine

Eduard Langenegger

Kamran B, Lankarani

Yee-Sin Leo

Rita Linko

Pei Liu

Faris Madanat

Elga Mayo-Montero

Allison McGeer

Ziad Memish

Gokhan Metan

Aukse Mickiene

Dragan Mikić

Kristin G. Mohn

Ahmadreza Moradi

Pagbajabyn Nymadawa

Maria E. Oliva

Mehpare Oskan

Dhruv Parekh

Mical Paul

Fernando P. Polack

Barbara A. Rath

Alejandro H. Rodríguez

Elena B. Sarrouf

Anna C. Seale

Bunyamin Sertogullarindan

Marilda M. Siqueira

Joanna Skręt-Magierło

Frank Stephan

Ewa Talarek

Julian W. Tang

Kelvin K. To

Antoni Torres

Selda H. Törün

Dat Tran

Timothy M. Uyeki

Annelies Van Zwol

Wendy Vaudry

Tjasa Vidmar

Renata T.C. Yokota

Paul Zarogoulidis



Abstract

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

Journal Article Type Article
Publication Date May 1, 2014
Journal Lancet Respiratory Medicine
Print ISSN 2213-2600
Electronic ISSN 2213-2619
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 2
Issue 5
APA6 Citation Muthuri, S. G., Venkatesan, S., Myles, P. R., Leonardi-Bee, J., Al Khuwaitir, T. S., Al Mamun, A., …Nguyen-Van-Tam, J. (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. Lancet Respiratory Medicine, 2(5), doi:10.1016/S2213-2600(14)70041-4
DOI https://doi.org/10.1016/S2213-2600%2814%2970041-4
Publisher URL http://dx.doi.org/10.1016/S2213-2600(14)70041-4
Related Public URLs http://www.sciencedirect.com/science/article/pii/S2213260014700414
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
Additional Information Copyright Elsevier 2014

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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