Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility : A case-only study
Montes, Ariana (Hospital Clínico Universitario (Santiago de Compostela, Galícia))
Perez-Pampin, Eva (Hospital Clínico Universitario (Santiago de Compostela, Galícia))
Navarro-Sarabia, Federica (Hospital Universitario Virgen Macarena (Sevilla, Andalusia))
Moreira, Virginia (Hospital Universitario Virgen Macarena (Sevilla, Andalusia))
Rodríguez de la Serna, Arturo (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Magallares López, Berta Paula (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Vasilopoulos, Yiannis (University of Thessaly (Grècia))
Sarafidou, Theologia (University of Thessaly (Grècia))
Fernández-Nebro, Antonio (Universidad de Málaga)
Ordóñez, María del Carmen (Universidad de Málaga)
Narváez, Javier (Hospital Universitari de Bellvitge)
Cañete, Juan D. (Hospital Clínic i Provincial de Barcelona)
Márquez, Ana (Instituto de Parasitología y Biomedicina "López-Neyra")
Pascual-Salcedo, Dora (Hospital Universitario La Paz (Madrid))
Joven, Beatriz (Hospital Universitario 12 de Octubre (Madrid))
Carreira, Patrícia (Hospital Universitario 12 de Octubre (Madrid))
Moreno-Ramos, Manuel J. (Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Múrcia))
Caliz, Rafael (Hospital Universitario Virgen de las Nieves (Granada))
Ferrer, Miguel Ángel (Hospital Universitario Virgen de las Nieves (Granada))
Garcia-Portales, Rosa (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Blanco-García, F.J (Universidade de Santiago de Compostela)
Magro, César (Hospital Universitario San Cecilio (Granada))
Raya, Enrique (Hospital Universitario San Cecilio (Granada))
Valor, Lara (Hospital General Universitario Gregorio Marañón)
Alegre-Sancho, Juan José (Hospital Universitari Doctor Peset (València))
Balsa, Alejandro (Hospital Universitario La Paz (Madrid))
Martin, Javier (Instituto de Parasitología y Biomedicina "López-Neyra")
Plant, Darren (Central Manchester University Hospitals NHS Foundation Trust)
Isaacs, John (Newcastle University)
Morgan, Ann W. (University of Leeds (Regne Unit))
Barton, Anne (The University of Manchester)
Wilson, Anthony G. (University College Dublin)
Gómez-Reino, Juan J. (Universidade de Santiago de Compostela)
Gonzalez, Antonio (Hospital Clínico Universitario (Santiago de Compostela, Galícia))
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2015
Resum:	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.
Ajuts:	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
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	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
Publicat a:	Arthritis research & therapy, Vol. 17 Núm. 1 (march 2015) , p. 63, ISSN 1478-6362

DOI: 10.1186/s13075-015-0571-z
PMID: 25885039

12 p, 1.6 MB

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