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

PRIDE Consortium Investigators, 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. DenholmSamuel 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, Rita Linko, Pei Liu, Faris Madanat, Elga Mayo-Montero, Allison McGeer, Ziad Memish, Gokhan Metan, Aukse Mickiene, Dragan Mikic, Kristin G.I. Mohn, Ahmadreza Moradi, Pagbajabyn Nymadawa, Maria E. Oliva, Mehpare Ozkan, 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 Skret-Magierlo, Frank Stephan, Ewa Talarek, Julian W. Tang, Kelvin K.W. To, Antoni Torres, Selda H. Törün, Dat Tran, Timothy M. Uyeki, Annelies van Zwol, Wendy Vaudry, Tjasa Vidmar, Renata T.C. Yokota, Paul Zarogoulidis, Jonathan S. Nguyen-van-Tam*

*Corresponding author for this work

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Abstract

Background: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their eff ectiveness 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 signifi cant 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.

Original languageEnglish
Pages (from-to)395-404
Number of pages10
JournalThe Lancet Respiratory Medicine
Volume2
Issue number5
DOIs
Publication statusPublished - May 2014
Externally publishedYes

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