IL6R polymorphisms can serve as a potential biomarker in predicting response to sarilumab in RA patients

According to a recent study published in Arthritis Research and Therapy, individuals with rheumatoid arthritis (RA) may have their response to sarilumab predicted by single-nucleotide polymorphisms (SNPs) in the IL6R gene, as well as anticipate potential adverse reactions. 

Conducted by Sainz and colleagues, the retrospective cohort study involved 62 patients treated with sarilumab. The primary objective was to investigate whether specific SNPs in the IL6R gene could serve as predictive indicators for both the effectiveness and toxicity of the treatment. The DNA samples obtained from these patients were genotyped for six previously identified SNPs in the IL6R gene (rs12083537, rs11265618, rs4329505, rs2228145, rs4537545, and rs4845625). 

The study results revealed that three SNPs (rs4845625, rs4329505, rs11265618) exhibited significant associations with specific response outcomes, such as disease activity score 28 (DAS28) improvement, DAS28-low disease activity (LDA), and clinical disease activity index (CDAI)-LDA. Similarly, five out of the six SNPs (rs2228145, rs4329505, rs11265618, rs4537545, rs4845625) demonstrated significant associations with adverse events, including hepatotoxicity and dyslipidemia. 

Sarilumab, a biologic drug designed to modify diseases, proves effective in treating patients with moderately to severely active RA who show intolerance or inadequate response to conventional synthetic DMARDs. It specifically binds to both soluble and membrane-bound IL-6 receptors, thereby inhibiting IL-6-mediated signaling. Clinical trials indicate a response rate of 40 to 45% at 6 months based on ACR50 criteria. Despite its notable efficacy, only 28-34% of patients in these studies achieved the therapeutic goal of DAS28-CRP remission. 

 The findings of the present study propose that SNPs can function as valuable biomarkers in predicting the response of RA patients to sarilumab treatment. Identifying genetic biomarkers for predicting response can assist in personalizing treatment strategies, potentially enhancing clinical outcomes. However, it is essential to note that more extensive research is necessary before these biomarkers can be routinely integrated into clinical practice. 


 Sainz L, Riera P, Moya P, Bernal S, Casademont J, Díaz-Torné C, et al. Impact of IL6R genetic variants on treatment   efficacy and toxicity response to sarilumab in rheumatoid arthritis. Arthritis Res Ther. 2023 Nov 24;25(1):226.