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Abstract
Background Rheumatoid arthritis (RA) treatment includes the use of the anti-CD20 monoclonal antibody rituximab (RTX). RTX acts through Fcγ-receptors (FCGR) on effector natural killer cells and macrophages and it can be administered effectively in RA and in lymphomas. Based on the results of in vitro experiments, its efficacy may depend of FCGR gene polymorphisms in both diseases.
Aim As genetic background of diseases and therapeutic efficacy (pharmacogenetics) may vary among different geographical regions, we wished to assess possible relationships between FCGR3A polymorphism and the therapeutic outcome of RTX therapy in a Hungarian RA cohort.
Patients and methods Altogether, 52 patients, 6 men and 46 women, were included in the study. Peripheral blood samples were used to determine FCGR3A polymorphism by genotyping using real-time PCR method.
Results The distribution of FCGR3A genotypes was 8 VV, 34 VF and 10 FF. Disease activity score 28 (DAS28) reductions in patients with VV, VF and FF genotypes were 1.98±0.54 (p=0.008 between DAS28 before and after treatment), 2.07±0.23 (p<0.001) and 1.59±0.52 (p=0.014), respectively. Significant differences in DAS28 reductions on treatment were found between VF heterozygotes and FF homozygotes (p=0.032), as well as between heterozygotes and all (VV+FF) homozygotes (p=0.017). Furthermore, significantly more VV (62.5%; p=0.030) and VF (64.7%; p=0.015) patients achieved low disease activity compared with FF subjects (30.0%).
Conclusion Our results suggest that FCGR3A polymorphism may predict more effective disease activity reduction by RTX. Furthermore, carrying the V allele may also be associated with better therapeutic response in Hungarian patients with RA.
- rheumatoid arthritis
- dmards (biologic)
- pharmacogenetics
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Footnotes
Contributors IP performed the experiments and drafted the manuscript. SS and ZS performed data analysis, revised manuscript. KH performed data analysis and statistics. LV supervised the work, drafted the protocol and read the manuscript.
Funding The work was supported by the European Union and the State of Hungary co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 ‘National Excellence Program’ (ZS); also by the European Union grant GINOP-2.3.2-15-2016-00015 (ZS).
Competing interests None declared.
Patient consent Obtained.
Ethics approval The study protocol was approved by the Institutional Review Board of University of Debrecen.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The corresponding author can be contacted regarding additional data.