Gene Polymorphisms Predict Response to Tocilizumab, Rituximab in RA

The presence of the FCGR2A rs1801274-TT genotype and FCGR3A rs396991-G allele may act as significant predictors of the response to tocilizumab and rituximab therapy in patients with rheumatoid arthritis (RA), according to the results of a retrospective prospective cohort study published in The Journal of Clinical Pharmacology.

The investigators sought to evaluate the effect of clinical, biochemical, and genetic factors on the response in 142 patients with RA. Of the participants, 61.26% were treated with tocilizumab and 38.73% were treated with rituximab. The variables assessed included the European League Against Rheumatism (EULAR) response, remission, low disease activity, and improvement in Disease Activity Score in 28 joints (DAS28) at 6, 12, and 18 months.

Tocilizumab-treated patients who carried the FCGR3A rs396991-TT genotype demonstrated significantly higher EULAR responses (odds ratio [OR], 5.075; 95% CI, 1.20-21.23; P = .027) at 12 months. Moreover, patients who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve at the initiation of therapy showed a satisfactory EULAR response, higher remission, and greater improvement in DAS28 at 6 months. Subcutaneous tocilizumab administration was associated with higher rates of remission at 6 months and improved low disease activity rate at 12 months. Furthermore, younger age at initiation of tocilizumab therapy was associated with a satisfactory EULAR response at 18 months, as well as greater remission rates at 6 and 12 months.

In contrast, rituximab-treated patients who carried the FCGR2A rs1801274-TT genotype demonstrated higher EULAR responses at 6 months (OR, 4.861; 95% CI, 1.11-21.12;
P =.035), 12 months (OR, 4.667; 95% CI, 0.90-24.12; P =.066), and 18 months (OR, 2.487; 95% CI, 0.35-17.31; P =.357); higher remission (OR, 10.625; 95% CI, 1.07-105.47; P =.044) at 6 months; and greater improvement in DAS28 at 12 months  (95% CI, –0.15 to 1.71; P =.098) and 18 months (95% CI, 0.19-2.63; P =.025).

Patients treated with rituximab who had received a lower number of prior bDMARDs reported higher rates of remission at 12 months. Moreover, the presence of the FCGR3A rs396991-G allele in patients who received rituximab was associated with improvement in the rate of low disease activity (OR, 4.904; 95% CI, 0.84-28.48; P =.077) and significantly greater improvement in DAS28 (95% CI, –1.98 to –0.18; P =.021) at 18 months.

The investigators concluded that the FCGR3A rs396991-TT genotype, subcutaneous administration, higher baseline values of DAS28, being bDMARD-naïve, and younger age at initiation of treatment were all linked to a better response to tocilizumab therapy. In patients treated with rituximab, better responses were reported in patients with the FCGR2A rs1801274-TT genotype, the FCGR3A rs396991-G allele, and fewer prior bDMARDs.

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Reference

Jiménez Morales A, Maldonado-Montoro M, Martínez de la Plata JE, et al. FCGR2A/FCGR3A gene polymorphisms and clinical variables as predictors of response to tocilizumab and rituximab in patients with rheumatoid arthritis [published online November 20, 2018]. J Clin Pharmacol. doi:10.1002/jcph.1341