Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study
Por:
Montes A, Perez-Pampin E, Navarro-Sarabia F, Moreira V, de la Serna AR, Magallares B, Vasilopoulos Y, Sarafidou T, Fernández-Nebro A, Ordóñez Mdel C, Narváez J, Cañete JD, Marquez A, Pascual-Salcedo D, Joven B, Carreira P, Moreno-Ramos MJ, Caliz R, Ferrer MA, Garcia-Portales R, Blanco FJ, Magro C, Raya E, Valor L, Alegre-Sancho JJ, Balsa A, Martin J, Plant D, Isaacs J, Morgan AW, Barton A, Wilson AG, Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS, Gómez-Reino JJ and Gonzalez A
Publicada:
18 mar 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 (Delta 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 Delta 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.
Filiaciones:
Montes A:
Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria - Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
Navarro-Sarabia F:
Rheumatology Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain.
de la Serna AR:
Rheumatology Unit, Hospital Santa Creu e San Pau, Barcelona, Spain.
Vasilopoulos Y:
Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
Fernández-Nebro A:
Servicio de Reumatología, HRU Carlos Haya, Universidad de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain.
Narváez J:
Department of Rheumatology, Hospital Universitario de Bellvitge, Barcelona, Spain.
Cañete JD:
Rheumatology Unit, Hospital Clinic, Barcelona, Spain.
Marquez A:
Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
Pascual-Salcedo D:
Department of Immunology, Instituto de Investigación Hospital Universitario La Paz, Hospital La Paz, Madrid, Spain.
Joven B:
Department of Rheumatology, Hospital 12 de Octubre, Madrid, Spain.
Moreno-Ramos MJ:
Department of Rheumatology, Hospital Virgen de la Arrixaca, Murcia, Spain.
Caliz R:
Rheumatology Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Garcia-Portales R:
Department of Rheumatology, Hospital Virgen de la Victoria, Málaga, Spain.
Blanco FJ:
Rheumatology Department, Instituto de Investigacion Biomedica-Complejo Hospitalario Universitario A Coruna, A Coruna, Spain.
Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
Magro C:
Department of Rheumatology, Hospital Clínico San Cecilio, Granada, Spain.
Valor L:
Rheumatology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
:
Department of Rheumatology, Hospital Doctor Peset, Valencia, Spain.
Balsa A:
Department of Rheumatology, Instituto de Investigación Hospital Universitario La Paz, Hospital Universitario La Paz, Madrid, Spain.
Plant D:
NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Isaacs J:
Musculoskeletal Research Group, Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle, UK.
National Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, Newcastle, UK.
Morgan AW:
Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James's University Hospital, University of Leeds, Leeds, UK.
NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Barton A:
Arthritis Research UK-Centre for Genetics and Genomics, The University of Manchester, Manchester, UK.
Wilson AG:
University College Dublin, Dublin, Ireland.
Gonzalez A:
Laboratorio Investigacion 10, Hospital Clinico Universitario de Santiago, Edificio de consultas, planta -2 Travesia de Choupana, sn, Santiago de Compostela, 15706, Spain.
Green Published, gold, Green Accepted
|