Impact of Single-Nucleotide Polymorphisms of CTLA-4, CD80 and CD86 on the Effectiveness of Abatacept in Patients with Rheumatoid Arthritis
Metadatos
Mostrar el registro completo del ítemAutor
Márquez Pete, Noelia; Maldonado Montoro, María del Mar; Pérez Ramírez, Cristina; Sánchez Martín, Almudena; Martínez de la Plata, Juan Enrique; Martínez Martínez, Fernando; Cáliz Cáliz, Antonio Rafael; Daddaoua, Abdelali; Ramírez Tortosa, María Carmen; Jiménez Morales, AlbertoEditorial
Mdpi
Materia
Rheumatoid arthritis Abatacept CTLA4 Effectiveness Polymorphism
Fecha
2020-11-11Referencia bibliográfica
Marquez Pete, N., Maldonado Montoro, M. D. M., Pérez Ramírez, C., Sánchez Martín, A., Martínez de la Plata, J. E., Martínez Martínez, F., ... & Jiménez Morales, A. (2020). Impact of Single-Nucleotide Polymorphisms of CTLA-4, CD80 and CD86 on the Effectiveness of Abatacept in Patients with Rheumatoid Arthritis. Journal of personalized medicine, 10(4), 220. [doi:10.3390/jpm10040220]
Patrocinador
University of Granada; Fundación de Investigación Biosanitaria de Andalucía Oriental (FIBAO); ERDF funds (EU) from the Instituto de Salud Carlos III PT13/0010/0039Resumen
Abatacept (ABA) is used as a first-line treatment in patients diagnosed with moderate and
severe rheumatoid arthritis (RA). The interindividual response to ABA therapy is very variable in
these patients. The objective of our study was therefore to investigate the role of polymorphisms of the
CTLA-4, CD80 and CD86 genes, as well as that of clinical factors of the disease, in the response toABAin
patients with RA. A retrospective cohort study was carried out in 109 patients receiving treatment with
ABA and diagnosed with RA. The genetic variables were analyzed using real-time PCR with TaqMan®
probes. The patients were classified according to the European League Against Rheumatism (EULAR)
criteria at 6 and 12 months from start of treatment. The independent variables associated with higher
EULAR response were lower duration of previous biologic disease-modifying anti-rheumatic drugs
and lower baseline values of the disease activity score 28 after 6 months of ABA treatment; and lower
baseline patient’s visual analogue scale (PVAS) after 12 months. In addition, a significant association
was found between duration of ABA treatment, non-administration of concomitant glucocorticoids
and lower baseline values of the number of inflamed joints and erythrocyte sedimentation rate clinical
variables, with remission of the disease after 6 months’ treatment with ABA. Finally, remission of
the disease after 12 months’ treatment with ABA was associated with earlier age at start of ABA
therapy and lower number of previous biologic therapies (BTs). The CTLA-4 rs5742909-T allele and
the CTLA-4 rs231775-G allele were found to be associated with satisfactory EULAR response and low
disease activity (LDA) after 12 months’ treatment with ABA (CTLA-4 rs5742909 T vs. CC; OR = 5.88; CI95% = 1.48–23.29 and OR = 4.75; CI95% = 1.35–17.94, respectively, and CTLA-4 rs231775 G vs. AA,
OR = 3.48; CI95% = 1.20–10.09 and OR = 4.68; CI95% = 1.49–17.94, respectively). In conclusion, patients
with RA treated with ABA showed better EULAR response and LDA rate when they had the CTLA-4
rs5742909-T or CTLA-4 rs231775-G polymorphisms; furthermore, this remission rate increased in
patients that began ABA treatment earlier, those with a lower number of previous BTs and those with
a lower PVAS value.