Influence of the FCGR2A rs1801274 and FCGR3A rs396991 Polymorphisms on Response to Abatacept in Patients with Rheumatoid Arthritis

Noelia Márquez Pete; María Del Mar Maldonado Montoro; Cristina Pérez Ramírez; Fernando Martínez Martínez; Juan Enrique Martínez de la Plata; Abdelali Daddaoua; Alberto Jiménez Morales

doi:10.3390/jpm11060573

Influence of the FCGR2A rs1801274 and FCGR3A rs396991 Polymorphisms on Response to Abatacept in Patients with Rheumatoid Arthritis

J Pers Med. 2021 Jun 18;11(6):573. doi: 10.3390/jpm11060573.

Authors

Noelia Márquez Pete¹, María Del Mar Maldonado Montoro², Cristina Pérez Ramírez^{1

3}, Fernando Martínez Martínez⁴, Juan Enrique Martínez de la Plata⁵, Abdelali Daddaoua⁶, Alberto Jiménez Morales¹

Affiliations

¹ Pharmacy Service, Pharmacogenetics Unit, University Hospital Virgen de las Nieves, 18014 Granada, Spain.
² Clinical Analysis Service, Hospital Campus de la Salud, 18016 Granada, Spain.
³ Center of Biomedical Research, Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology "José Mataix", University of Granada, Avda. del Conocimiento s/n., 18016 Granada, Spain.
⁴ Department of Pharmacy and Pharmaceutical Technology, Social and Legal Assistance Pharmacy Section, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain.
⁵ Pharmacy Service, Hospital de Poniente-El Ejido, 04700 El Ejido, Spain.
⁶ Department of Biochemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain.

Abstract

Abatacept (ABA) is an immunosuppressant indicated for treatment of rheumatoid arthritis (RA). Effectiveness might be influenced by clinical RA variants and single-nucleotide polymorphisms (SNPs) in genes encoding protein FCGR2A (His131Arg) and FCGR3A (Phe158Val) involved in pharmacokinetics of ABA. An observational cohort study was conducted in 120 RA Caucasian patients treated with ABA for 6 and 12 months. Patients with the FCGR2A rs1801274-AA genotype (FCGR2A-p.131His) showed a better EULAR response (OR = 2.43; 95% CI = 1.01-5.92) at 12 months and low disease activity (LDA) at 6 months (OR = 3.16; 95% CI = 1.19-8.66) and 12 months (OR = 6.62; 95% CI = 1.25-46.89) of treatment with ABA. A tendency was observed towards an association between the FCGR3A rs396991-A allele (FCGR3A-p.158Phe) and better therapeutic response to ABA after 12 months of treatment (p = 0.078). Moreover, we found a significant association between the low-affinity FCGR2A/FCGR3A haplotypes variable and LDA after 12 months of ABA treatment (OR = 1.59; 95% CI = 1.01-2.58). The clinical variables associated with better response to ABA were lower age at starting ABA (OR = 1.06; 95% CI = 1.02-1.11) and greater duration of ABA treatment (OR = 1.02; 95% CI = 1.01-1.04), lower duration of previous biological therapies (OR = 0.99; 95% CI = 0.98-0.99), non-administration of concomitant disease-modifying antirheumatic drugs (DMARDs) (OR = 24.53; 95% CI = 3.46-523.80), non-use of concomitant glucocorticoids (OR = 0.12; 95% CI = 0.02-0.47), monotherapy (OR = 19.22; 95% CI = 2.05-343.00), lower initial patient's visual analogue scale (PVAS) value (OR = 0.95; 95% CI = 0.92-0.97), and lower baseline ESR (OR = 0.92; 95% CI = 0.87-0.97). This study showed that high-affinity FCGR2A-p.131His variant, low-affinity FCGR3A-p.158Phe variant, and combined use of FCGR2A/FCGR3A genetic variations could affect ABA effectiveness. Further studies will be required to confirm these results.

Keywords: FCGR2A; FCGR3A; abatacept; effectiveness; polymorphisms; rheumatoid arthritis.