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Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study

Lookup NU author(s): Professor John Isaacs

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Abstract

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.


Publication metadata

Author(s): Montes A, Perez-Pampin E, Navarro-Sarabia F, Moreira V, de la Sema AR, Magallares B, Vasilopoulos Y, Sarafidou T, Fernandez-Nebro A, Ordonez MD, Narvaez J, Canete 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, Gomez-Reino JJ, Gonzalez A, BRAGGSS

Publication type: Article

Publication status: Published

Journal: Arthritis Research & Therapy

Year: 2015

Volume: 17

Online publication date: 18/03/2015

Acceptance date: 20/02/2015

ISSN (print): 1478-6354

ISSN (electronic): 1478-6362

Publisher: BioMed Central Ltd.

URL: http://dx.doi.org/10.1186/s13075-015-0571-z

DOI: 10.1186/s13075-015-0571-z


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