Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: An individual participant data meta-analysis

Muthuri, S. G.; Venkatesan, S.; Myles, P. R.; Leonardi-Bee, J.; Lim, W. S.; Al Mamun, A.; Anovadiya, A. P.; Araujo, W. N.; Azziz-Baumgartner, E.; Baez, C.; Bantar, C.; Barhoush, M. M.; Bassetti, M.; Beovic, B.; Bingisser, R.; Bonmarin, I.; Borja-Aburto, V. H.; Cao, B.; Carratala, J.; Cuezzo, M. R.; Denholm, J. T.; Dominguez, S. R.; Duarte, P. A. D.; Dubnov-Raz, G.; Echavarria, M.; Fanella, S.; Fraser, J.; Gao, Z.; Gerardin, P.; Giannella, M.; Gubbels, S.; Herberg, J.; Higuera Iglesias, A. L.; Hoeger, P. H.; Hoffmann, M.; Hu, X.; Islam, Q. T.; Jimenez, M. F.; Kandeel, A.; Keijzers, G.; Khalili, H.; Khandaker, G.; Knight, M.; Kusznierz, G.; Kuzman, I.; Kwan, A. M. C.; Lahlou Amine, I.; Langenegger, E.; Lankarani, K. B.; Leo, Y. -S.; Linko, R.; Liu, P.; Madanat, F.; Manabe, T.; Mayo-Montero, E.; Mcgeer, A.; Memish, Z. A.; Metan, G.; Mikic, D.; Mohn, K. G. I.; Moradi, A.; Nymadawa, P.; Ozbay, B.; Ozkan, M.; Parekh, D.; Paul, M.; Poeppl, W.; Polack, F. P.; Rath, B. A.; Rodriguez, A. H.; Siqueira, M. M.; Skret-Magierlo, J.; Talarek, E.; Tang, J. W.; Torres, A.; Torun, S. H.; Tran, D.; Uyeki, T. M.; van Zwol, A.; Vaudry, W.; Velyvyte, D.; Vidmar, T.; Zarogoulidis, P.; Nguyen-Van-Tam, J. S.; de Lourdes Aguiar-Oliveira, M.; Al Khuwaitir, T. S. A.; Al Masri, M.; Amin, R.; Ballester-Orcal, E.; Bao, J.; Basher, A.; Bautista, E.; Bertisch, B.; Bettinger, J.; Booy, R.; Bouza, E.; Bozkurt, I.; Burgmann, H.; Celjuska-Tosev, E.; Chan, K. K. C.; Chen, Y.; Chinbayar, T.; Cilloniz, C.; Cox, R. J.; Sarrouf, E. B.; Cui, W.; Dashti-Khavidaki, S.; Du, B.; El Rhaffouli, H.; Escobar, H.; Florek-Michalska, A.; Gerrard, J.; Gormley, S.; Gotberg, S.; Honarvar, B.; Hu, J.; Kemen, C.; Koay, E. S.; Kojic, M.; Kudo, K.; Kyaw, W. M.; Leibovici, L.; X. -L., Li; Li, H.; Libster, R.; Loh, T. P.; Macbeth, D.; Maltezos, E.; Marcone, D. N.; Marczynska, M.; Mastalir, F. P.; Mickiene, A.; Moghadami, M.; Moriconi, L.; Oliva, M. E.; Pecavar, B.; Poliquin, P. G.; Rahman, M.; Rascon-Pacheco, A.; Refaey, S.; Schweiger, B.; Seale, A. C.; Sertogullarindan, B.; Smith, F. G.; Somer, A.; Souza, T. M.; Stephan, F.; Tabarsi, P.; Tripathi, C.; Viasus, D.; Yu, Q.; Zhang, W.; Zuo, W.

doi:10.1111/irv.12363

Background: The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. Methods: A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. Results: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64-1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44-1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71-1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55-0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54-0·85; P = 0·001)]. Conclusions: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: An individual participant data meta-analysis

Muthuri S. G.;Venkatesan S.;Myles P. R.;Leonardi-Bee J.;Lim W. S.;Al Mamun A.;Anovadiya A. P.;Araujo W. N.;Azziz-Baumgartner E.;Baez C.;Bantar C.;Barhoush M. M.;Bassetti M.;Beovic B.;Bingisser R.;Bonmarin I.;Borja-Aburto V. H.;Cao B.;Carratala J.;Cuezzo M. R.;Denholm J. T.;Dominguez S. R.;Duarte P. A. D.;Dubnov-Raz G.;Echavarria M.;Fanella S.;Fraser J.;Gao Z.;Gerardin P.;Giannella M.;Gubbels S.;Herberg J.;Higuera Iglesias A. L.;Hoeger P. H.;Hoffmann M.;Hu X.;Islam Q. T.;Jimenez M. F.;Kandeel A.;Keijzers G.;Khalili H.;Khandaker G.;Knight M.;Kusznierz G.;Kuzman I.;Kwan A. M. C.;Lahlou Amine I.;Langenegger E.;Lankarani K. B.;Leo Y. -S.;Linko R.;Liu P.;Madanat F.;Manabe T.;Mayo-Montero E.;Mcgeer A.;Memish Z. A.;Metan G.;Mikic D.;Mohn K. G. I.;Moradi A.;Nymadawa P.;Ozbay B.;Ozkan M.;Parekh D.;Paul M.;Poeppl W.;Polack F. P.;Rath B. A.;Rodriguez A. H.;Siqueira M. M.;Skret-Magierlo J.;Talarek E.;Tang J. W.;Torres A.;Torun S. H.;Tran D.;Uyeki T. M.;van Zwol A.;Vaudry W.;Velyvyte D.;Vidmar T.;Zarogoulidis P.;Nguyen-Van-Tam J. S.;de Lourdes Aguiar-Oliveira M.;Al Khuwaitir T. S. A.;Al Masri M.;Amin R.;Ballester-Orcal E.;Bao J.;Basher A.;Bautista E.;Bertisch B.;Bettinger J.;Booy R.;Bouza E.;Bozkurt I.;Burgmann H.;Celjuska-Tosev E.;Chan K. K. C.;Chen Y.;Chinbayar T.;Cilloniz C.;Cox R. J.;Sarrouf E. B.;Cui W.;Dashti-Khavidaki S.;Du B.;El Rhaffouli H.;Escobar H.;Florek-Michalska A.;Gerrard J.;Gormley S.;Gotberg S.;Honarvar B.;Hu J.;Kemen C.;Koay E. S.;Kojic M.;Kudo K.;Kyaw W. M.;Leibovici L.;Li X. -L.;Li H.;Libster R.;Loh T. P.;Macbeth D.;Maltezos E.;Marcone D. N.;Marczynska M.;Mastalir F. P.;Mickiene A.;Moghadami M.;Moriconi L.;Oliva M. E;Pecavar B.;Poliquin P. G;Rahman M.;Rascon-Pacheco A.;Refaey S.;Schweiger B.;Seale A. C.;Sertogullarindan B.;Smith F. G.;Somer A.;Souza T. M.;Stephan F.;Tabarsi P.;Tripathi C.;Viasus D.;Yu Q.;Zhang W.;Zuo W.

2016-01-01

Abstract

Background: The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. Methods: A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. Results: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64-1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44-1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71-1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55-0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54-0·85; P = 0·001)]. Conclusions: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.