Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: a prospective multicohort study of the ABIRISK consortium
In: PLoS Medicine, 2020
Online
academicJournal
Zugriff:
BackgroundBiopharmaceutical 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 findingsThe 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 Polymorphisms (SNPs) and 38 ...
Titel: |
Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: a prospective multicohort study of the ABIRISK consortium
|
---|---|
Autor/in / Beteiligte Person: | Hassler, S. ; Bachelet, D. ; Duhaze, J. ; Szely, N. ; Gleizes, A. ; Abina, S.H.B. ; Aktas, O. ; Auer, M. ; Avouac, J. ; Birchler, M. ; Bouhnik, Y. ; Brocq, O. ; Buck-Martin, D. ; Cadiot, G. ; Carbonnel, F. ; Chowers, Y. ; Comabella, M. ; Derfuss, T. ; Vries, N. de ; Donnellan, N. ; Doukani, A. ; Guger, M. ; Hartung, H.P. ; Havrdova, E.K. ; Hemmer, B. ; Huizinga, T. ; Ingenhoven, K. ; Hyldgaard-Jensen, P.E. ; Jury, E.C. ; Khalil, M. ; Kieseier, B. ; Lauren, A. ; Lindberg, R. ; Loercher, A. ; Maggi, E. ; Manson, J. ; Mauri, C. ; Oumoussa, B.M. ; Montalban, X. ; Nachury, M. ; Nytrova, P. ; Richez, C. ; Ryner, M. ; Sellebjerg, F. ; Sievers, C. ; Sikkema, D. ; Soubrier, M. ; Tourdot, S. ; Trang, C. ; Vultaggio, A. ; Warnke, C. ; Spindeldreher, S. ; Donnes, P. ; Hickling, T.P. ; Mery, A.H. ; Allez, M. ; Deisenhammer, F. ; Fogdell-Hahn, A. ; Mariette, X. ; Pallardy, M. ; Broet, P. ; Consortium, ABIRISK |
Link: | |
Zeitschrift: | PLoS Medicine, 2020 |
Veröffentlichung: | 2020 |
Medientyp: | academicJournal |
DOI: | 10.1371/journal.pmed.1003348 |
Sonstiges: |
|