Effect of Fcγ-receptor 3a () gene polymorphisms on rituximab therapy in Hungarian patients with rheumatoid arthritis.

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 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 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 polymorphism by genotyping using real-time PCR method.

RESULTS

The distribution of 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 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.