A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial

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• dc.contributor.author Arora, Ashwani K.
• dc.contributor.author Chinsky, Kenneth
• dc.contributor.author Keller, Claus
• dc.contributor.author Mayers, Irvin
• dc.contributor.author Pascual Guàrdia, Sergi, 1979-
• dc.contributor.author Pérez Vera, Mercè
• dc.contributor.author Lambert, Christophe
• dc.contributor.author Lombardi, Stefano
• dc.contributor.author Rondini, Simona
• dc.contributor.author Tian, Suan
• dc.contributor.author Ulloa-Montoya, Fernando
• dc.contributor.author Moraschini, Luca
• dc.contributor.author Casula, Daniela
• dc.contributor.author NTHi-Mcat-002 study group
• dc.date.accessioned 2023-02-17T07:04:56Z
• dc.date.available 2023-02-17T07:04:56Z
• dc.date.issued 2022
• dc.description.abstract Background: An investigational vaccine containing non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) surface proteins did not show vaccine efficacy (VE) against combined moderate and severe (moderate/severe) exacerbations in a randomised, observer-blinded, placebo-controlled phase 2b trial of patients with chronic obstructive pulmonary disease (COPD). Nevertheless, observations on rates of severe exacerbations and hospitalisations encouraged further evaluation. Methods: Patients with stable COPD (moderate to very severe airflow limitation, Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2-4), 40-80 years and at least one moderate/severe exacerbation in the last year received two doses of NTHi-Mcat vaccine or placebo plus standard care. Secondary analyses were conducted on VE against exacerbations according to severity. Potential predictive factors at baseline for VE against severe exacerbations were explored in post-hoc analyses. Results: Of 606 patients enrolled, 571 were included in the efficacy analysis (279 in NTHi-Mcat vaccine group, 292 in placebo group). VE against severe acute exacerbations of COPD (AECOPD) in various subgroups was 52.11 % (p = 0.015; frequent exacerbators), 65.43 % (p = 0.015; baseline GOLD grade 4), 38.24 % (p = 0.034; previous pneumococcal and/or influenza vaccination). VE was 52.49 % (p = 0.044) for the 6-12 months period after 1 month post-dose 2. Multivariable analysis identified two factors (frequent exacerbator status plus inhaled corticosteroid use at baseline) associated with significant VE against severe AECOPD; in this subpopulation, VE was 74.99 % (p < 0.001). Conclusion: Results suggest potential efficacy with the NTHi-Mcat vaccine against severe exacerbations in certain patients with COPD, in particular those who have frequent exacerbations and use inhaled corticosteroids. This potential signal requires confirmation in an appropriately designed prospective clinical trial. Trial registration: ClinicalTrials.gov, NCT03281876.
• dc.format.mimetype application/pdf
• dc.identifier.citation Arora AK, Chinsky K, Keller C, Mayers I, Pascual-Guardia S, Vera MP, Lambert C, Lombardi S, Rondini S, Tian S, Ulloa-Montoya F, Moraschini L, Casula D; NTHi-Mcat-002 study group. A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial. Vaccine. 2022 Sep 29;40(41):5924-32. DOI: 10.1016/j.vaccine.2022.08.053
• dc.identifier.doi http://dx.doi.org/10.1016/j.vaccine.2022.08.053
• dc.identifier.issn 0264-410X
• dc.identifier.uri http://hdl.handle.net/10230/55813
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Vaccine. 2022 Sep 29;40(41):5924-32
• dc.rights © 2022 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Chronic obstructive pulmonary disease
• dc.subject.keyword Clinical trial
• dc.subject.keyword Exacerbation
• dc.subject.keyword Moraxella catarrhalis
• dc.subject.keyword Non-typeable Haemophilus influenzae
• dc.subject.keyword Vaccination
• dc.title A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion