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| Página principal > Artículos > Artículos publicados > Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility : |
| Fecha: | 2015 |
| Resumen: | Introduction: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). Methods: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (DAS28) and the European League Against Rheumatism (EULAR) response criteria. Results: An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0. 03). This association was confirmed in the replications (P = 0. 02 and 0. 08, respectively) leading to a global association (P = 0. 001) that involved a mean difference in DAS28 of 0. 4 units between compatible and incompatible patients (2. 3 ± 1. 5 in compatible patients vs. 1. 9 ± 1. 5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0. 03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. Conclusions: Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA. |
| Ayudas: | Ministerio de Ciencia e Innovación PI11/01048 Ministerio de Ciencia e Innovación RD08/0075/0019 Ministerio de Economía y Competitividad RD12/0009/0008 Ministerio de Economía y Competitividad PI12/01909 |
| Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió publicada |
| Materia: | Adalimumab ; Adult ; Antirheumatic Agents ; Arthritis, Rheumatoid ; Base Sequence ; Female ; Genotype ; Humans ; Immunoglobulin Allotypes ; Immunoglobulin G ; Infliximab ; Male ; Middle Aged ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Treatment Outcome ; Tumor Necrosis Factor-alpha |
| Publicado en: | Arthritis research & therapy, Vol. 17 Núm. 1 (march 2015) , p. 63, ISSN 1478-6362 |
12 p, 1.6 MB |