Safety of baricitinib in vaccinated patients with severe and critical COVID-19 sub study of the randomised Bari-SolidAct trial.

Autor:	Viermyr HK; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway., Tonby K; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Infectious Diseases, Oslo University Hospital Ullevål, Oslo, Norway., Ponzi E; Department of Research Support for Clinical Trials, Oslo University Hospital, Oslo, Norway., Trouillet-Assant S; Centre International de Recherche en Infectiologie (CIRI), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France; Joint Research Unit Hospices Civils de Lyon-bioMerieux S.A., Hôpital Lyon Sud, Pierre-Bénite, France., Poissy J; Université Lille, Inserm U1285, CHU Lille, Pôle de Médecine Intensive-Réanimatin, CNRS, UMR 8576, France; Université Lille, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), F-59000, Lille, France., Arribas JR; Infectious Diseases Unit, Internal Medicine Department, La Paz University Hospital, IdiPAZ, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain., Dyon-Tafani V; Centre International de Recherche en Infectiologie (CIRI), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France., Bouscambert-Duchamp M; Hospices Civils de Lyon, Laboratoire de Virologie, Institut des Agents Infectieux de Lyon, Centre National de Référence des Virus Respiratoires France Sud, F-69317, Lyon, France; Université Claude Bernard Lyon 1, Virpath, CIRI, INSERM U1111, CNRS UMR5308, ENS Lyon, F-69372, Lyon, France., Assoumou L; Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique (IPLESP), Paris, France., Halvorsen B; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Tekin NB; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Diallo A; ANRS, Maladies Infectieuses Emergentes, F-75015, Paris, France; Institut National de la Santé et de la Recherche Médicale, INSERM, F-75013, Paris, France., De Gastines L; ANRS, Maladies Infectieuses Emergentes, F-75015, Paris, France; Institut National de la Santé et de la Recherche Médicale, INSERM, F-75013, Paris, France., Munthe LA; Department of Immunology, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for B Cell Malignancies, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Precision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Murphy SL; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Ueland T; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway., Michelsen AE; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Lund-Johansen F; Department of Immunology, Oslo University Hospital, Oslo, Norway; Precision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Aukrust P; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Mootien J; Intensive Care Unit, Antibiotic Stewardship Team, Groupe Hospitalier Région Mulhouse et Sud Alsace, Mulhouse, France., Dervieux B; Infectious Diseases Unit, Groupe Hospitalier Région Mulhouse et Sud Alsace, Mulhouse, France., Zerbib Y; Intensive Care Department, Amiens-Picardie University Hospital, Amiens, France., Richard JC; Medical Intensive Care Unit, Hospices Civils de Lyon, Croix-Rousse Hospital - Université Lyon 1, Lyon, France; CREATIS INSERM 1044 CNRS 5220, Villeurbanne, France., Prével R; CHU Bordeaux, Medical Intensive Care Unit, Bordeaux, France; Univ Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Inserm UMR 1045, Bordeaux, France., Malvy D; Department of Infectious and Tropical Diseases, University Hospital, UMR 1219 Inserm/EMR 271 IRD, University of Bordeaux, Bordeaux, France., Timsit JF; AP-HP, Bichat Hospital, Medical and Infectious Diseases ICU (MI2), F-75018, Paris, France; Université Paris-Cité, INSERM, F-75018, Paris, France; OUCTOME REA Research Network, France., Peiffer-Smadja N; Université Paris Cité, Inserm, IAME, Paris, 75018, France; Service de Maladies Infectieuses et Tropicales, Hôpital Bichat Claude Bernard, AP-HP, Paris, 75018, France., Roux D; Université Paris Cité, AP-HP, Hôpital Louis Mourier, DMU ESPRIT, Service de Médecine Intensive Réanimation, Colombes, France., Piroth L; Infectious Diseases Department, University Hospital, Dijon, France; INSERM CIC 1432, University of Burgundy, Dijon, France., Ait-Oufella H; Service de Médecine Intensive-Réanimation, Hôpital Saint-Antoine, AP-HP, Sorbonne Université, Paris, F-75012, France., Vieira C; Centro Hospitalar Universitário de Lisboa Central, Hospital Curry Cabral, Department of Intensive Care Medicine - Lisbon, Portugal., Dalgard O; Department of Infectious Diseases, Oslo University Hospital Ullevål, Oslo, Norway; Department of Infectious Diseases, Akershus University Hospital, Norway., Heggelund L; Department of Internal Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Norway; Department of Clinical Science, Bergen Integrated Diagnostic Stewardship Cluster, Faculty of Medicine, University of Bergen, Bergen, Norway., Müller KE; Department of Internal Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Norway; Department of Clinical Science, Bergen Integrated Diagnostic Stewardship Cluster, Faculty of Medicine, University of Bergen, Bergen, Norway., Møller JH; Department of Intensive Care Medicine, Stavanger University Hospital, Stavanger, Norway., Kildal AB; Department of Anesthesiology and Intensive Care, University Hospital of North Norway, Tromsø, Norway; Faculty of Health Sciences, UIT The Arctic University of Norway, Norway., Skogen V; Department of Infectious Diseases, University Hospital of North Norway, Tromsø, Norway; Faculty of Health Sciences, UIT The Arctic University of Norway, Norway., Aballi S; Department of Infectious Diseases, Østfold Hospital Kalnes, Grålum, Norway., Sjøberg Øgaard JD; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Dyrhol-Riise AM; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Infectious Diseases, Oslo University Hospital Ullevål, Oslo, Norway., Tveita A; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Internal Medicine, Bærum Hospital, Vestre Viken Hospital Trust, 1346, Gjettum, Norway., Alirezaylavasani A; Department of Immunology, Oslo University Hospital, Oslo, Norway., Costagliola D; Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique (IPLESP), Paris, France., Yazdanpanah Y; Infectious and Tropical Diseases Department, Bichat - Claude Bernard Hospital, AP-HP Nord-Université Paris Cité, Paris, France; IAME INSERM UMR 1137, Université Paris Cité, Paris, France; ANRS, Maladies Infectieuses Emergentes, F-75015, Paris, France; Institut National de la Santé et de la Recherche Médicale, INSERM, F-75013, Paris, France., Olsen IC; Department of Research Support for Clinical Trials, Oslo University Hospital, Oslo, Norway., Dahl TB; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Kared H; Department of Immunology, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for B Cell Malignancies, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Precision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Holten AR; Department of Infectious Diseases, Oslo University Hospital Ullevål, Oslo, Norway; Department of Acute Medicine, Oslo University Hospital, Oslo, Norway., Trøseid M; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway. Electronic address: marius.troseid@medisin.uio.no.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2024 Dec 27; Vol. 111, pp. 105511. Date of Electronic Publication: 2024 Dec 27.
DOI:	10.1016/j.ebiom.2024.105511
Abstrakt:	Background: The Bari-SolidAct randomized controlled trial compared baricitinib with placebo in patients with severe COVID-19. A post hoc analysis revealed a higher incidence of serious adverse events (SAEs) among SARS-CoV-2-vaccinated participants who had received baricitinib. This sub-study aimed to investigate whether vaccination influences the safety profile of baricitinib in patients with severe COVID-19. Methods: Biobanked samples from 146 participants (55 vaccinated vs. 91 unvaccinated) were analysed longitudinally for inflammation markers, humoral responses, tissue viral loads, and plasma viral antigens on days 1, 3, and 8. High-dimensional analyses, including RNA sequencing and flow cytometry, were performed on available samples. Mediation analyses were used to assess relationships between SAEs, baseline-adjusted biomarkers, and treatment-vaccination status. Findings: Vaccinated participants were older, more frequently hospitalized, had more comorbidities, and exhibited higher nasopharyngeal viral loads. Baricitinib treatment did not affect antibody responses or viral clearance, but reduced markers of T-cell and monocyte activation compared to placebo (sCD25, sCD14, sCD163, sTIM-3). Age, baseline levels of plasma viral antigen, and several inflammatory markers, as well as IL-2, IL-6, Neopterin, CXCL16, sCD14, and suPAR on day 8 were associated with the occurrence of SAEs. However, mediation analyses of markers linked to SAEs, baricitinib treatment, or vaccination status did not reveal statistically significant interactions between vaccination status and SAEs. Interpretation: This sub-study did not identify any virus- or host-related biomarkers significantly associated with the interaction between SARS-CoV-2 vaccination status and the safety of baricitinib. However, caution should be exercised due to the moderate sample size. Funding: EU Horizon 2020 (grant number 101015736). Competing Interests: Declaration of interests MT has been a pro bono member of the scientific advisory board for Lilly. JP reports lecture fees from Gilead, Shionogi, and Mundipharma, as well as payment for expert testimony from Gilead, Shionogi, Eumedica, and Pfizer, and support for attending meetings from Gilead, and Shionogi. ARH reports personal fee from Pfizer (2021) for lectures outside the submitted work. RP reports personal fees from MSD (2024) for one lecture and from Gilead (2023) and Pfizer (2023) for congress attendance. LAM reports Helse Sør-Øst UiO and Research Council of Norway grant for developing cellular analyses of COVID-19 (2020–2022), grant from KG Jebsen Stiftelsen, and grant from The Coalition for Epidemic Preparedness Innovation to monitor immune responses in patients (2021–2023). DC reports personal fees from Pfizer (2022) for a lecture outside the submitted work. BD reports support from Amgen for congress attendance. J-FT report honoraria from Shionogi, Merck, Pfizer, and Advanz as well as participation in advisory board for Gilead, Merck, Menarini, and Biomerieux. AEM reports stocks in Pfizer. LP reports honoraria from Gilead, GSK, Moderna, Pfizer, and ViiV Healthcare, as well as support for attending meetings from MSD and Pfizer. YZ reports payments for lectures from Gilead, Shionogi, and Mundipharma, payment for expert testimony from Gilead, Shionogi, Eumedica, and Pfizer, as well as support for attending meetings from Gilead and Shionogi. MB reports support for attending meetings from Gilead and Shionogi. JM reports support for attending meetings from Pfizer and Menarini as well as participation in advisory board for MSD. All other authors have nothing to declare. (Copyright © 2024. Published by Elsevier B.V.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu