Nirsevimab for Prevention of Hospitalizations Due to RSV in Infants.

Humans Infant Antibodies, Monoclonal, Humanized / administration & dosage Hospitalization Respiratory Syncytial Virus Infections / prevention & control Respiratory Syncytial Virus, Human Respiratory Tract Infections / prevention & control Injections, Intramuscular

Journal

The New England journal of medicine

ISSN: 1533-4406

Titre abrégé: N Engl J Med

Pays: United States

ID NLM: 0255562

Informations de publication

Date de publication:
28 Dec 2023

Historique:

medline: 3 1 2024

pubmed: 2 1 2024

entrez: 29 12 2023

Statut: ppublish

Résumé

The safety of the monoclonal antibody nirsevimab and the effect of nirsevimab on hospitalizations for respiratory syncytial virus (RSV)-associated lower respiratory tract infection when administered in healthy infants are unclear. In a pragmatic trial, we randomly assigned, in a 1:1 ratio, infants who were 12 months of age or younger, had been born at a gestational age of at least 29 weeks, and were entering their first RSV season in France, Germany, or the United Kingdom to receive either a single intramuscular injection of nirsevimab or standard care (no intervention) before or during the RSV season. The primary end point was hospitalization for RSV-associated lower respiratory tract infection, defined as hospital admission and an RSV-positive test result. A key secondary end point was very severe RSV-associated lower respiratory tract infection, defined as hospitalization for RSV-associated lower respiratory tract infection with an oxygen saturation of less than 90% and the need for supplemental oxygen. A total of 8058 infants were randomly assigned to receive nirsevimab (4037 infants) or standard care (4021 infants). Eleven infants (0.3%) in the nirsevimab group and 60 (1.5%) in the standard-care group were hospitalized for RSV-associated lower respiratory tract infection, which corresponded to a nirsevimab efficacy of 83.2% (95% confidence interval [CI], 67.8 to 92.0; P<0.001). Very severe RSV-associated lower respiratory tract infection occurred in 5 infants (0.1%) in the nirsevimab group and in 19 (0.5%) in the standard-care group, which represented a nirsevimab efficacy of 75.7% (95% CI, 32.8 to 92.9; P = 0.004). The efficacy of nirsevimab against hospitalization for RSV-associated lower respiratory tract infection was 89.6% (adjusted 95% CI, 58.8 to 98.7; multiplicity-adjusted P<0.001) in France, 74.2% (adjusted 95% CI, 27.9 to 92.5; multiplicity-adjusted P = 0.006) in Germany, and 83.4% (adjusted 95% CI, 34.3 to 97.6; multiplicity-adjusted P = 0.003) in the United Kingdom. Treatment-related adverse events occurred in 86 infants (2.1%) in the nirsevimab group. Nirsevimab protected infants against hospitalization for RSV-associated lower respiratory tract infection and against very severe RSV-associated lower respiratory tract infection in conditions that approximated real-world settings. (Funded by Sanofi and AstraZeneca; HARMONIE ClinicalTrials.gov number, NCT05437510).

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

In a pragmatic trial, we randomly assigned, in a 1:1 ratio, infants who were 12 months of age or younger, had been born at a gestational age of at least 29 weeks, and were entering their first RSV season in France, Germany, or the United Kingdom to receive either a single intramuscular injection of nirsevimab or standard care (no intervention) before or during the RSV season. The primary end point was hospitalization for RSV-associated lower respiratory tract infection, defined as hospital admission and an RSV-positive test result. A key secondary end point was very severe RSV-associated lower respiratory tract infection, defined as hospitalization for RSV-associated lower respiratory tract infection with an oxygen saturation of less than 90% and the need for supplemental oxygen.

RESULTS RESULTS

A total of 8058 infants were randomly assigned to receive nirsevimab (4037 infants) or standard care (4021 infants). Eleven infants (0.3%) in the nirsevimab group and 60 (1.5%) in the standard-care group were hospitalized for RSV-associated lower respiratory tract infection, which corresponded to a nirsevimab efficacy of 83.2% (95% confidence interval [CI], 67.8 to 92.0; P<0.001). Very severe RSV-associated lower respiratory tract infection occurred in 5 infants (0.1%) in the nirsevimab group and in 19 (0.5%) in the standard-care group, which represented a nirsevimab efficacy of 75.7% (95% CI, 32.8 to 92.9; P = 0.004). The efficacy of nirsevimab against hospitalization for RSV-associated lower respiratory tract infection was 89.6% (adjusted 95% CI, 58.8 to 98.7; multiplicity-adjusted P<0.001) in France, 74.2% (adjusted 95% CI, 27.9 to 92.5; multiplicity-adjusted P = 0.006) in Germany, and 83.4% (adjusted 95% CI, 34.3 to 97.6; multiplicity-adjusted P = 0.003) in the United Kingdom. Treatment-related adverse events occurred in 86 infants (2.1%) in the nirsevimab group.

CONCLUSIONS CONCLUSIONS

Nirsevimab protected infants against hospitalization for RSV-associated lower respiratory tract infection and against very severe RSV-associated lower respiratory tract infection in conditions that approximated real-world settings. (Funded by Sanofi and AstraZeneca; HARMONIE ClinicalTrials.gov number, NCT05437510).

Identifiants

DOI: 10.1056/NEJMoa2309189 PMID: 38157500

pubmed: 38157500

doi: 10.1056/NEJMoa2309189

doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0

nirsevimab VRN8S9CW5V

Banques de données

ClinicalTrials.gov

['NCT05437510']

Types de publication

Journal Article Multicenter Study Pragmatic Clinical Trial Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

Pagination

2425-2435

Subventions

Organisme : Sanofi

ID : N/A

Organisme : AstraZeneca

ID : N/A

Investigateurs

Jacques Brouard (J)

Andre Leke (A)

Veronique Brevaut-Malaty (V)

Chloe Epiard (C)

Florence Flamein (F)

Ralph Epaud (R)

David Somerville (D)

Franck Thollot (F)

Phu My Tran Dinh (PMT)

Mathie Lorrot (M)

Andreas Werner (A)

Rachel Froget (R)

Hasinirina Razafimahefa (H)

Michael Fayon (M)

Camille Brehin (C)

Pascal Boileau (P)

Kim-An Nguyen (KA)

Cecile Guiheneuf (C)

Claire Lefevre (C)

Claire Sarreau (C)

Fabienne Kochert (F)

Frederic Huet (F)

Elisa Seror (E)

Fabienne Cahn-Sellem (F)

Nadege Delavie (N)

Christophe Batard (C)

François Corrard (F)

Morched Zouari (M)

Nathalie Gelbert-Baudino (N)

Diane Carriere (D)

Zoha Maakaroun-Vermesse (Z)

Jean Gaschignard (J)

Stephane Rioualen (S)

Frederic Dugelay (F)

Alain Wollner (A)

Kai Kassmann (K)

Didier Pinquier (D)

Jean-Francois Delobbe (JF)

Robert Cohen (R)

Anne Cheve (A)

Anne Bourlet (A)

Christele Gras-Le Guen (C)

Benedicte Nold (B)

Bergengere Kireche (B)

Anne-Sylvestre Michot-Cottias (AS)

Francine Lecaillier (F)

Myrna Achkar (M)

Lisa Giovannini-Chami (L)

Aimen Bsila (A)

Laura Vivalda (L)

Florence Goehringer (F)

Amelie Poidvin (A)

Christine Magendie (C)

Emilie Georget (E)

Blandine Desse (B)

Vincent Gajdos (V)

Eric Jeziorski (E)

Sanaa Naji (S)

Christian Petit (C)

Mallorie Mondenx (M)

Emmanuelle Rondeleux (E)

Aurelie Morand (A)

Cecile Kerdudo-Veau (C)

Blandine Prevost (B)

Alexandra David (A)

Gaelle Cornen (G)

Christine Devulder (C)

Sven Wellmann (S)

Cordula Koerner-Rettberg (C)

Otto Laub (O)

Hartmut Scheele (H)

Manfred Praun (M)

Markus Knuf (M)

Martin Wetzke (M)

Helmut Pabel (H)

Andreas Petri (A)

Ulrich Thome (U)

Falko Panzer (F)

Hans Fuchs (H)

Jana-Katharina Dieks (JK)

Martin Oliver Bauer (MO)

Jost Richter (J)

Katrin Biebach (K)

Frank Radowsky (F)

Matthias Donner (M)

Katja Denneberg (K)

Jurgen Funck (J)

Soeren Westerholt (S)

Michael Horn (M)

Malte Cremer (M)

Wolfgang Kamin (W)

Ulf Schulze-Sturm (U)

Nikolaos Konstantopoulos (N)

Brigitte Wilmsmeyer (B)

Thomas Voelkl (T)

Martina von Poblotzki (M)

Andreas Mueller (A)

Egbert Leonhardt (E)

Siegfried Simmet (S)

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Commentaires et corrections

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