Giuseppe
Emeritus
[Source: The Lancet Infectious Diseases, full text: (LINK). Abstract, edited.]
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The Lancet Infectious Diseases, Early Online Publication, 19 March 2013
doi:10.1016/S1473-3099(13)70046-X
AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial
Original Text
Prof Janet E McElhaney MD a, Prof Jiri Beran MD b *, Jeanne-Marie Devaster MD c *, Meral Esen MD d *, Prof Odile Launay MD e f g h *, Prof Geert Leroux-Roels MD i *, Guillermo M Ruiz-Palacios MD j *, Gerrit A van Essen MD k *, Adrian Caplanusi MD l ?, Carine Claeys MD l ?, Christelle Durand MSc c ?, Prof Xavier Duval MD m n ?, Mohamed El Idrissi MSc l ?, Prof Ann R Falsey MD o ?, Gregory Feldman MD p ?, Prof Sharon E Frey MD q ?, Florence Galtier MD r s ?, Prof Shinn-Jang Hwang MD t u ?, Bruce L Innis MD v ?, Martina Kovac MD c ?, Peter Kremsner MD d ?, Prof Shelly McNeil MD w ?, Andrzej Nowakowski PhD x y ?, Prof Jan Hendrik Richardus PhD z ?, Andrew Trofa MD v ?, Dr Lidia Oostvogels MD l, for the Influence65 study group
Summary
Background
We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people.
Methods
We did a randomised trial in 15 countries worldwide during the 2008?09 (year 1) and 2009?10 (year 2) influenza seasons. Eligible participants aged at least 65 years who were not in hospital or bedridden and were without acute illness were randomly assigned (1:1) to receive either AS03-adjuvanted TIV or non-adjuvanted TIV. Randomisation was done in an internet-based system, with a blocking scheme and stratification by age (65?74 years and 75 years or older). Participants were scheduled to receive one vaccine in each year, and remained in the same group in years 1 and 2. Unmasked personnel prepared and gave the vaccines, but participants and individuals assessing any study endpoint were masked. The coprimary objectives were to assess the relative efficacy of the vaccines and lot-to-lot consistency of the AS03-adjuvanted TIV (to be reported elsewhere). For the first objective, the primary endpoint was relative efficacy of the vaccines for prevention of influenza A (excluding A H1N1 pdm09) or B, or both, that was confirmed by PCR analysis in year 1 (lower limit of two-sided 95% CI had to be greater than zero to establish superiority). From Nov 15, to April 30, in both years, participants were monitored by telephone or site contact and home visits every week or 2 weeks to identify cases of influenza-like illness. After onset of suspected cases, we obtained nasal and throat swabs to identify influenza RNA with real-time PCR. Efficacy analyses were done per protocol. This trial is registered with ClinicalTrials.gov, number NCT00753272.
Findings
We enrolled 43 802 participants, of whom 21 893 were assigned to and received the AS03-adjuvanted TIV and 21 802 the non-adjuvanted TIV in year 1. In the year 1 efficacy cohort, fewer participants given AS03-adjuvanted than non-adjuvanted TIV were infected with influenza A or B, or both (274 [1?27%, 95% CI 1?12?1?43] of 21 573 vs 310 [1?44%, 1?29?1?61] of 21 482; relative efficacy 12?11%, 95% CI −3?40 to 25?29; superiority not established). Fewer participants in the year 1 efficacy cohort given AS03-adjuvanted TIV than non-adjuvanted TIV were infected with influenza A (224 [1?04%, 95% CI 0?91?1?18] vs 270 [1?26, 1?11?1?41]; relative efficacy 17?53%, 95% CI 1?55?30?92) and influenza A H3N2 (170 [0?79, 0?67?0?92] vs 205 [0?95, 0?83?1?09]; post-hoc analysis relative efficacy 22?0%, 95% CI 5?68?35?49).
Interpretation
AS03-adjuvanted TIV has a higher efficacy for prevention of some subtypes of influenza than does a non-adjuvanted TIV. Future influenza vaccine studies in elderly people should be based on subtype or lineage-specific endpoints.
Funding
GlaxoSmithKline Biologicals SA.
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a Health Sciences North and Advanced Medical Research Institute of Canada, Sudbury, ON, Canada; b Vaccination and Travel Medicine Centre, Hradec Kralove, Czech Republic; c GlaxoSmithKline Vaccines, Rixensart, Belgium; d Institut f?r Tropenmedizin, T?bingen, Germany; e Inserm, French network of clinical investigation in vaccinology, Paris, France; f Universit? Paris-Descartes, Paris, France; g Inserm, CIC BT505, Paris, France; h Assistance Publique-H?pitaux de Paris, H?pital Cochin, CIC de Vaccinologie Cochin-Pasteur, Paris, France; i Centre for Vaccinology, Ghent University and Ghent University Hospital, Ghent, Belgium; j Department of Infectious Diseases, Instituto Nacional de Ciencias M?dicas y Nutrici?n Salvador Zubir?n, Mexico City, Mexico; k Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; l GlaxoSmithKline Vaccines, Wavre, Belgium; m H?pital Bichat Claude Bernard, GH BICHAT, Paris, France; n Inserm, CIC 007, French network of clinical investigation in vaccinology, Paris, France; o University of Rochester Medical Center, Rochester, NY, USA; p S Carolina Pharmaceutical Research, Spartanburg, SC, USA; q Saint Louis University Medical Center, St Louis, MO, USA; r CHRU de Montpellier, H?pital Saint Eloi, Montpellier, France; s Inserm, CIC 1001, French network of clinical investigation in vaccinology, Montpellier, France; t Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; u National Yang-Ming University School of Medicine, Taipei, Taiwan; v GlaxoSmithKline Vaccines, King of Prussia, PA, USA; w VG Site Infectious Diseases, Queen Elizabeth Health Sciences Centre, Dalhousie University, Halifax, NS, Canada; x Family Medicine Centre, Lubart?w, Poland; y Department of Gynaecology and Oncologic Gynaecology, Military Institute of Medicine, Warsaw, Poland; z GGD Rotterdam-Rijnmond, Rotterdam, Netherlands
Correspondence to: Dr Lidia Oostvogels, GlaxoSmithKline Vaccines, Parc de la Noire Epine, 1300 Wavre, Belgium
* Listed in alphabetical order
? Also listed in alphabetical order
-doi:10.1016/S1473-3099(13)70046-X
AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial
Original Text
Prof Janet E McElhaney MD a, Prof Jiri Beran MD b *, Jeanne-Marie Devaster MD c *, Meral Esen MD d *, Prof Odile Launay MD e f g h *, Prof Geert Leroux-Roels MD i *, Guillermo M Ruiz-Palacios MD j *, Gerrit A van Essen MD k *, Adrian Caplanusi MD l ?, Carine Claeys MD l ?, Christelle Durand MSc c ?, Prof Xavier Duval MD m n ?, Mohamed El Idrissi MSc l ?, Prof Ann R Falsey MD o ?, Gregory Feldman MD p ?, Prof Sharon E Frey MD q ?, Florence Galtier MD r s ?, Prof Shinn-Jang Hwang MD t u ?, Bruce L Innis MD v ?, Martina Kovac MD c ?, Peter Kremsner MD d ?, Prof Shelly McNeil MD w ?, Andrzej Nowakowski PhD x y ?, Prof Jan Hendrik Richardus PhD z ?, Andrew Trofa MD v ?, Dr Lidia Oostvogels MD l, for the Influence65 study group
Summary
Background
We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people.
Methods
We did a randomised trial in 15 countries worldwide during the 2008?09 (year 1) and 2009?10 (year 2) influenza seasons. Eligible participants aged at least 65 years who were not in hospital or bedridden and were without acute illness were randomly assigned (1:1) to receive either AS03-adjuvanted TIV or non-adjuvanted TIV. Randomisation was done in an internet-based system, with a blocking scheme and stratification by age (65?74 years and 75 years or older). Participants were scheduled to receive one vaccine in each year, and remained in the same group in years 1 and 2. Unmasked personnel prepared and gave the vaccines, but participants and individuals assessing any study endpoint were masked. The coprimary objectives were to assess the relative efficacy of the vaccines and lot-to-lot consistency of the AS03-adjuvanted TIV (to be reported elsewhere). For the first objective, the primary endpoint was relative efficacy of the vaccines for prevention of influenza A (excluding A H1N1 pdm09) or B, or both, that was confirmed by PCR analysis in year 1 (lower limit of two-sided 95% CI had to be greater than zero to establish superiority). From Nov 15, to April 30, in both years, participants were monitored by telephone or site contact and home visits every week or 2 weeks to identify cases of influenza-like illness. After onset of suspected cases, we obtained nasal and throat swabs to identify influenza RNA with real-time PCR. Efficacy analyses were done per protocol. This trial is registered with ClinicalTrials.gov, number NCT00753272.
Findings
We enrolled 43 802 participants, of whom 21 893 were assigned to and received the AS03-adjuvanted TIV and 21 802 the non-adjuvanted TIV in year 1. In the year 1 efficacy cohort, fewer participants given AS03-adjuvanted than non-adjuvanted TIV were infected with influenza A or B, or both (274 [1?27%, 95% CI 1?12?1?43] of 21 573 vs 310 [1?44%, 1?29?1?61] of 21 482; relative efficacy 12?11%, 95% CI −3?40 to 25?29; superiority not established). Fewer participants in the year 1 efficacy cohort given AS03-adjuvanted TIV than non-adjuvanted TIV were infected with influenza A (224 [1?04%, 95% CI 0?91?1?18] vs 270 [1?26, 1?11?1?41]; relative efficacy 17?53%, 95% CI 1?55?30?92) and influenza A H3N2 (170 [0?79, 0?67?0?92] vs 205 [0?95, 0?83?1?09]; post-hoc analysis relative efficacy 22?0%, 95% CI 5?68?35?49).
Interpretation
AS03-adjuvanted TIV has a higher efficacy for prevention of some subtypes of influenza than does a non-adjuvanted TIV. Future influenza vaccine studies in elderly people should be based on subtype or lineage-specific endpoints.
Funding
GlaxoSmithKline Biologicals SA.
_________
a Health Sciences North and Advanced Medical Research Institute of Canada, Sudbury, ON, Canada; b Vaccination and Travel Medicine Centre, Hradec Kralove, Czech Republic; c GlaxoSmithKline Vaccines, Rixensart, Belgium; d Institut f?r Tropenmedizin, T?bingen, Germany; e Inserm, French network of clinical investigation in vaccinology, Paris, France; f Universit? Paris-Descartes, Paris, France; g Inserm, CIC BT505, Paris, France; h Assistance Publique-H?pitaux de Paris, H?pital Cochin, CIC de Vaccinologie Cochin-Pasteur, Paris, France; i Centre for Vaccinology, Ghent University and Ghent University Hospital, Ghent, Belgium; j Department of Infectious Diseases, Instituto Nacional de Ciencias M?dicas y Nutrici?n Salvador Zubir?n, Mexico City, Mexico; k Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; l GlaxoSmithKline Vaccines, Wavre, Belgium; m H?pital Bichat Claude Bernard, GH BICHAT, Paris, France; n Inserm, CIC 007, French network of clinical investigation in vaccinology, Paris, France; o University of Rochester Medical Center, Rochester, NY, USA; p S Carolina Pharmaceutical Research, Spartanburg, SC, USA; q Saint Louis University Medical Center, St Louis, MO, USA; r CHRU de Montpellier, H?pital Saint Eloi, Montpellier, France; s Inserm, CIC 1001, French network of clinical investigation in vaccinology, Montpellier, France; t Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; u National Yang-Ming University School of Medicine, Taipei, Taiwan; v GlaxoSmithKline Vaccines, King of Prussia, PA, USA; w VG Site Infectious Diseases, Queen Elizabeth Health Sciences Centre, Dalhousie University, Halifax, NS, Canada; x Family Medicine Centre, Lubart?w, Poland; y Department of Gynaecology and Oncologic Gynaecology, Military Institute of Medicine, Warsaw, Poland; z GGD Rotterdam-Rijnmond, Rotterdam, Netherlands
Correspondence to: Dr Lidia Oostvogels, GlaxoSmithKline Vaccines, Parc de la Noire Epine, 1300 Wavre, Belgium
* Listed in alphabetical order
? Also listed in alphabetical order
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