Genetic polymorphisms of FcGR2B and adalimumab effectiveness in Colombian patients with rheumatoid arthritis. Cases-controls study

Abstract

Background Adalimumab is one of the main drugs used in the treatment of rheumatoid arthritis (RA); however, the effectiveness of the drug may be affected by the genetic variability of each patient. This study aims to investigate the therapeutic failure of adalimumab associated to genetic polymorphisms of FcGR2B. Methods A case-control study in Colombian patients diagnosed with RA was carried out. The data was collected based on clinical information reported by the patients and by genotyping and sequencing information through “Targeted Sequencing” and “Exomic Sequencing”. The cases in the study were patients in treatment with adalimumab, with therapeutic failure, on anti-TNF-α treatment for at least three months, and with exome sequencing data. The controls were patients with past treatment with adalimumab, with therapeutic effectiveness, on anti-TNF-α treatment for at least three months, and with exome sequencing data. The collected data was summarized by interquartile range and compared by chi-square test. Results 222 patients were selected, 21 of whom met the inclusion criteria and matched for sex and age. The gene that contained the highest number of SNPs was HLA-DRB1 and the one with the second highest number of SNPs was HLA-DQA2. The other genes with great relevance were FCGR3B and FCGR2B. The risk of ineffectiveness was higher in patients with the presence of Genetic polymorphisms of FcGR2B rs6666965 (OR = 23.3; P = 0.0121). While this risk was associated with other SNPs such as rs78763831 (OR = 17. 8; P = 0.0.065), rs4778636 (OR = 15.9; P = 0.0778) and rs3933769 (OR = 7.5; P = 0.0.0974) it was not statistically significant, despite the strong association. Conclusion Patients diagnosed with RA with genetic polymorphisms of FcGR2B, mainly by the presence of the SNP rs6666965 have a positive association with therapeutic failure of adalimumab. The identification of these genetic variables can contribute to the availability of pharmacogenetics tests for adalimumab and the generation of a pharmacogenomics basis for patients with RA. Trial registration NCT03352622