Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium
In: ISSN: 1549-1277, 2020
Online
academicJournal
Zugriff:
International audience ; Background: Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited.Methods and findings: The European consortium ABIRISK (Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) conducted a clinical and genomic multicohort prospective study of 560 patients with multiple sclerosis (MS, n = 147), rheumatoid arthritis (RA, n = 229), Crohn's disease (n = 148), or ulcerative colitis (n = 36) treated with 8 different biopharmaceuticals (etanercept, n = 84; infliximab, n = 101; adalimumab, n = 153; interferon [IFN]-beta-1a intramuscularly [IM], n = 38; IFN-beta-1a subcutaneously [SC], n = 68; IFN-beta-1b SC, n = 41; rituximab, n = 31; tocilizumab, n = 44) and followed during the first 12 months of therapy for time to ADA development. From the bioclinical data collected, we explored the relationships between patient-related factors and the occurrence of ADAs. Both baseline and time-dependent factors such as concomitant medications were analyzed using Cox proportional hazard regression models. Mean age and disease duration were 35.1 and 0.85 years, respectively, for MS; 54.2 and 3.17 years for RA; and 36.9 and 3.69 years for inflammatory bowel diseases (IBDs). In a multivariate Cox regression model including each of the clinical and genetic factors mentioned hereafter, among the clinical factors, immunosuppressants (adjusted hazard ratio [aHR] = 0.408 [95% confidence interval (CI) 0.253-0.657], p < 0.001) and antibiotics (aHR = 0.121 [0.0437-0.333], p < 0.0001) were independently negatively associated with time to ADA development, whereas infections during the study (aHR = 2.757 [1.616-4.704], p < 0.001) and tobacco smoking (aHR = 2.150 [1.319-3.503], p < 0.01) were positively associated. 351,824 Single-Nucleotide ...
| Titel: |
Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium
|
|---|---|
| Autor/in / Beteiligte Person: | Hässler, Signe ; Bachelet, Delphine ; Duhazé, Julianne ; Szely, Natacha ; Gleizes, Aude ; Hacein-Bey Abina, Salima ; Aktas, Orhan ; Auer, Michael ; Avouac, Jérôme ; Birchler, Mary ; Bouhnik, Yoram ; Brocq, Olivier ; Buck-Martin, Dorothea ; Cadiot, Guillaume ; Carbonnel, Franck ; Chowers, Yehuda ; Comabella, Manuel ; Derfuss, Tobias ; de Vries, Niek ; Donnellan, Naoimh ; Doukani, Abiba ; Guger, Michael ; Hartung, Hans-Peter ; Kubala Havrdova, Eva ; Hemmer, Bernhard ; Huizinga, Tom ; Ingenhoven, Kathleen ; Hyldgaard-Jensen, Poul Erik ; Jury, Elizabeth ; Khalil, Michael ; Kieseier, Bernd ; Laurén, Anna ; Lindberg, Raija ; Loercher, Amy ; Maggi, Enrico ; Manson, Jessica ; Mauri, Claudia ; Mohand Oumoussa, Badreddine ; Montalban, Xavier ; Nachury, Maria ; Nytrova, Petra ; Richez, Christophe ; Ryner, Malin ; Sellebjerg, Finn ; Sievers-Stober, Claudia ; Sikkema, Dan ; Soubrier, Martin ; Tourdot, Sophie ; Trang-Poisson, Caroline ; Vultaggio, Alessandra ; Warnke, Clemens ; Spindeldreher, Sebastian ; Dönnes, Pierre ; Hickling, Timothy ; Hincelin Mery, Agnès ; Allez, Matthieu ; Deisenhammer, Florian ; Fogdell-Hahn, Anna ; Mariette, Xavier ; Pallardy, Marc ; Broët, Philippe ; Centre de recherche en épidémiologie et santé des populations (CESP) ; Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay ; Immunologie - Immunopathologie - Immunothérapie CHU Pitié Salpêtrière (I3) ; CHU Charles Foix AP-HP ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU) ; Centre d'investigation clinique Biothérapie CHU Pitié-Salpêtrière (CIC-BTi) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) ; Institut de médecine et d'épidémiologie appliquée AP-HP Hôpital Bichat-Claude Bernard (IMEA) ; AP-HP - Hôpital Bichat - Claude Bernard Paris ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) ; Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital Montreal, Canada ; Université de Montréal (UdeM)-CHU Sainte Justine Montréal ; Inflammation, microbiome, immunosurveillance (MI2) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay ; Service de Médecine interne - Immunologie clinique Kremlin-Bicêtre ; Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre ; Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1267)) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité) ; Heinrich Heine Universität Düsseldorf = Heinrich Heine University Düsseldorf ; Innsbruck Medical University = Medizinische Universität Innsbruck (IMU) ; Institut Cochin (IC UM3 (UMR 8104 / U1016)) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité) ; Service de rhumatologie CHU Cochin ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin AP-HP ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) ; GlaxoSmithKline ; Glaxo Smith Kline ; Hôpital Beaujon AP-HP ; Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID) ; Hôpital Princesse Grace Monaco ; Technische Universität Munchen - Technical University Munich - Université Technique de Munich (TUM) ; Hôpital universitaire Robert Debré Reims (CHU Reims) ; Service d'Hépato-gastro-entérologie APHP Kremlin-Bicêtre ; University of Haifa Haifa ; Centre d'Esclerosi Múltiple de Catalunya (CemCat) ; University Hospital Basel Basel ; Université de Bâle = University of Basel = Basel Universität (Unibas) ; VU University Medical Center Amsterdam ; Royal Berkshire Hospital ; Plateforme Post-génomique de la Pitié-Salpêtrière (PASS-P3S) ; Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU) ; Kepler University Hospital ; Univerzita Karlova Praha, Česká republika = Charles University Prague, Czech Republic (UK) ; Medicine Charles University and General Faculty Hospital in Prague ; Munich Cluster for systems neurology Munich (SyNergy) ; Technische Universität Munchen - Technical University Munich - Université Technique de Munich (TUM)-Ludwig Maximilian University Munich = Ludwig Maximilians Universität München (LMU) ; Leiden University Medical Center (LUMC) ; Universiteit Leiden = Leiden University ; Danish Multiple Sclerosis Research Centre ; Copenhagen, Rigshospitalet ; Copenhagen University Hospital-Copenhagen University Hospital-University of Copenhagen = Københavns Universitet (UCPH) ; University College of London London (UCL) ; Medical University of Graz ; Malmö Högskola = Malmö University ; Università degli Studi di Firenze = University of Florence = Université de Florence (UniFI) ; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS ; University College London Hospitals (UCLH) ; St. Michael's Hospital ; University of Toronto ; Service des Maladies de l'Appareil Digestif et de la Nutrition CHRU Lille ; Hôpital Claude Huriez Lille ; Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille) ; Service de Rhumatologie CHU Pellegrin ; Groupe hospitalier Pellegrin ; Composantes innées de la réponse immunitaire et différenciation (CIRID) ; Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS) ; Department of Clinical Neuroscience Sotckholm ; Karolinska Institutet Stockholm ; Service de Rhumatologie CHU Clermont-Ferrand ; CHU Gabriel Montpied Clermont-Ferrand ; CHU Clermont-Ferrand-CHU Clermont-Ferrand ; Institut des Maladies de l'Appareil Digestif ; Université de Nantes (UN) ; Universitätsklinikum Köln (Uniklinik Köln) ; Novartis Institutes for BioMedical Research (NIBR) ; Integrated Biologix GmbH Basel ; SciCross, AB ; Pfizer ; Sanofi Aventis R&D Chilly-Mazarin ; Hopital Saint-Louis AP-HP (AP-HP) ; Centre de recherche en Immunologie des Infections virales et des maladies auto-immunes ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay ; Hôpital Paul Brousse ; Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse ; The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115303 , resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. BH received support from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). The biobank of the Department of Neurology as part of the Joint Biobank Munich in the framework of the German Biobank Node supported the study. OA received grants from the German Research Foundation (DFG) and the German Ministry of Education and Research (BMBF). TD’s institution received grants from the Swiss National Research Foundation, University of Basel, and Swiss MS Society. EKH and PN were supported by the Czech Ministry of Education research project PROGRES Q27/LF1 and MSMT-35199/2012-32. |
| Link: | |
| Zeitschrift: | ISSN: 1549-1277, 2020 |
| Veröffentlichung: | HAL CCSD ; Public Library of Science, 2020 |
| Medientyp: | academicJournal |
| DOI: | 10.1371/journal.pmed.1003348 |
| Schlagwort: |
|
| Sonstiges: |
|