FCGR2A/FCGR3A Gene Polymorphisms and Clinical Variables as Predictors of Response to Tocilizumab and Rituximab in Patients With Rheumatoid Arthritis.

Abstract

We evaluated the influence of clinical, biochemical, and genetic factors on response in 142 patients diagnosed with rheumatoid arthritis, of whom 87 patients were treated with tocilizumab (61.26%) and 55 patients were treated with rituximab (38.7%;) according to the variables European League Against Rheumatism (EULAR) response, remission, low disease activity, and improvement in Disease Activity Score, 28 joints (DAS28) at 6, 12, and 18months. A retrospective prospective cohort study was conducted. Patients carrying the FCGR3A rs396991-TT genotype treated with tocilizumab showed higher EULAR response (OR, 5.075; 95%CI, 1.20-21.33; P= .027) at 12months, those who were naive for biological disease-modifying antirheumatic drugs (bDMARDs) at the beginning of treatment showed satisfactory EULAR response, higher remission, and greater improvement in DAS28 at 6months. Younger age at start of tocilizumab treatment was associated with satisfactory EULAR response at 18months and greater remission at 6 and 18months. Subcutaneous tocilizumab administration was associated with higher remission at 6months and improved low disease activity rate at 12months. In patients treated with rituximab, carriers of the FCGR2A rs1801274-TT genotype had higher EULAR response at 6months (OR, 4.861; 95%CI, 1.11-21.12; P= .035), 12months (OR, 4.667; p= 0.066, 95%CI, 0.90-24.12; P = .066), and 18months (OR, 2.487; 95%CI, 0.35-17.31; P= .357), higher remission (OR: 10.625; p= 0.044, CI95% : 1.07, 105.47) at 6months, and greater improvement in DAS28 at 12months (B= 0.782; 95%CI, -0.15 to 1.71; P= .098) and 18months (B= 1.414; 95%CI, 0.19-2.63; P= .025). The FCGR3A rs396991-G allele was associated with improved low disease activity rate (OR, 4.904; 95%CI, 0.84-28.48; P= .077) and greater improvement in DAS28 (B= -1.083; 95%CI, -1.98 to -0.18; P= .021) at 18months. Patients with a lower number of previous biological therapies had higher remission at 12months. We suggest that the FCGR3A rs396991-TT genotype, higher baseline value of DAS28, subcutaneous tocilizumab administration, younger age at the beginning of treatment, and being bDMARD naive are associated with better response to tocilizumab. In patients treated with rituximab, we found better response in those patients with the FCGR2A rs1801274-TT genotype, the FCGR3A rs396991-G allele, and lower number of previous biological therapies.