Background/Purpose: Iguratimod (IGU) is a novel DMARD in rheumatoid arthritis (RA). The purpose of this study was to identify genetic predictors of response and adverse drug events (AEs) to IGU therapy in patients with RA.

Methods: Seven single nucleotide polymorphisms(SNPs) of enzyme and transporter proteins related to IGU, CYP1A2*1F(rs762551),CYP2C19*2 (rs4244285), NAT2(rs1495741),ABCB1(rs1045642,rs2032582C),ABCG2(rs2231142) and SLCO1B1 (rs4149036), were determined by a genotyping approach in 272 IGU treated RA patients. SNPs were evaluated using real-time polymerase chain reaction. The efficacy of the IGU therapy was estimated using EULAR good response criteria based on the DAS-28. All AEs were recorded.

Results: 21.69% patients (59/272) were good responders and 36.40% patients (99/272) had AEs. Unvariant analyses and multivariate analyses demonstrated that the ABCG2 A allele was associates with good response to IGU (OR=2.084, 95%CI 1.147-3.786, P=0.015; OR=1.944, 95%CI 1.038-3.641, P=0.038). NAT2 G carrier was significantly associated with less favorable response to IGU (OR=0.476, 95%CI 0.256-0.884, P=0.017; OR=0.498, 95% CI 0.256-0.967, P=0.029). CYP2C19*2 A carriers had higher risk for IGU-induced toxicity than did the GG genotyping (OR=2.122, 95%CI 1.273-3.537, P=0.004; OR=2. 368, 95%CI 1.395-4.019, P=0.001). No significant association was found between the genotypes of CYP1A2*1F, ABCB1 and SLCO1B1 SNP and the IGU response or AEs.

Conclusion: Our study suggests that ABCG2 (rs2231142), NAT2 (rs1495741) and CYP2C19*2 (rs4244285) genotyping may help to identify patients who will benefit from IGU treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/genetic-predictors-of-iguratimod-clinical-response-and-toxicity-in-patients-with-rheumatoid-arthritis/