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Impact of Single-Nucleotide Polymorphisms of CTLA-4, CD80 and CD86 on the Effectiveness of Abatacept in Patients with Rheumatoid Arthritis

1
Pharmacy Service. Pharmacogenetics Unit, University Hospital Virgen de las Nieves, Avda. Fuerzas Armadas, 2, 18014 Granada, Spain
2
Clinical Analysis Service, Hospital Campus de la Salud, Av. de la Investigación, 18016 Granada, Spain
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Pharmacy Service. Pharmacogenetics Unit, University Hospital Virgen Macarena, Dr. Fedriani, 3, 41009 Sevilla, Spain
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Pharmacy Service. Hospital de Poniente-El Ejido, Diseminado Ctra Almerimar, 31, 04700 El Ejido, Spain
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Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, 18071 Granada, Spain
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Department of Pharmacy and Pharmaceutical Technology. Social and Legal Assistance Pharmacy Section, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, 18071 Granada, Spain
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Rheumatology Service, University Hospital Virgen de las Nieves, Avda. Fuerzas Armadas, 2, 18014 Granada, Spain
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Department of Biochemistry, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, 18071 Granada, Spain
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
These authors also contributed equally to the work.
J. Pers. Med. 2020, 10(4), 220; https://doi.org/10.3390/jpm10040220
Received: 2 October 2020 / Revised: 11 November 2020 / Accepted: 11 November 2020 / Published: 11 November 2020
(This article belongs to the Section Pharmacogenetics)
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 to ABA in 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-4rs5742909-T allele and the CTLA-4rs231775-G allele were found to be associated with satisfactory EULAR response and low disease activity (LDA) after 12 months’ treatment with ABA (CTLA-4rs5742909 T vs. CC; OR = 5.88; CI95% = 1.48–23.29 and OR = 4.75; CI95% = 1.35–17.94, respectively, and CTLA-4rs231775 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. View Full-Text
Keywords: rheumatoid arthritis; abatacept; CTLA4; effectiveness; polymorphisms rheumatoid arthritis; abatacept; CTLA4; effectiveness; polymorphisms
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MDPI and ACS Style

Marquez Pete, N.; Maldonado Montoro, M.d.M.; Pérez Ramírez, C.; Sánchez Martín, A.; Martínez de la Plata, J.E.; Martínez Martínez, F.; Caliz Caliz, R.; Daddaoua, A.; Ramírez Tortosa, M.d.C.; Jiménez Morales, A. Impact of Single-Nucleotide Polymorphisms of CTLA-4, CD80 and CD86 on the Effectiveness of Abatacept in Patients with Rheumatoid Arthritis. J. Pers. Med. 2020, 10, 220. https://doi.org/10.3390/jpm10040220

AMA Style

Marquez Pete N, Maldonado Montoro MdM, Pérez Ramírez C, Sánchez Martín A, Martínez de la Plata JE, Martínez Martínez F, Caliz Caliz R, Daddaoua A, Ramírez Tortosa MdC, Jiménez Morales A. 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. 2020; 10(4):220. https://doi.org/10.3390/jpm10040220

Chicago/Turabian Style

Marquez Pete, Noelia, María del Mar Maldonado Montoro, Cristina Pérez Ramírez, Almudena Sánchez Martín, Juan Enrique Martínez de la Plata, Fernando Martínez Martínez, Rafael Caliz Caliz, Abdelali Daddaoua, María del Carmen Ramírez Tortosa, and Alberto Jiménez Morales. 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, no. 4: 220. https://doi.org/10.3390/jpm10040220

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