Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic pain and inflammation in the joints, causing physical impairment and reducing the quality of life of those affected. In recent decades, multiple immunosuppressive therapies called biologics have been developed, which have allowed better control of the disease with a significant positive impact on the lives of patients with RA. Biologics act by specifically blocking inflammatory pathways linked, among other things, to various interleukins in the immune system. Currently, there are no markers (clinical, analytical or genetic) that help us predict which biologic drug is most suitable for each patient.
Pharmacogenetics is the field of study that studies genetic variation between individuals and its effects on drug response or adverse effects, with the goal of providing the most personalized treatments possible. The most common changes responsible for variation in the human genome are single nucleotide polymorphisms (SNPs). In rheumatic diseases, there have been studies that link this variation to response to some immunosuppressive drugs, but there is little evidence linking genetic variation to interleukin-6 receptor inhibitor drugs, such as sarilumab.
We decided to conduct the first pharmacogenomic study in RA patients treated with sarilumab, evaluating polymorphisms in the interleukin-6 receptor gene. Specifically, we studied six of these genetic variants and their association with treatment response variables and adverse event effects in 62 patients with RA.
Three of the SNPs studied (rs4845625, rs4329505, and rs11265618) showed association with treatment response variables. We observed up to 30% higher improvement depending on the genetic variations presented by the patients. In particular, the results related to SNP rs4845625 stand out, as they are consistent with the different treatment response variables studied and with the results of a similar study we conducted using tocilizumab, another biologic with a similar mechanism of action.
Regarding adverse effects of treatment, all evaluated polymorphisms (except rs12083537) were associated with dyslipidemia (high cholesterol) or altered liver function tests. However, these adverse effects appear to be minor in the overall context of the disease.
In conclusion, the results of this study demonstrate for the first time that certain genetic variants in the IL-6 receptor gene lead to differential treatment responses or adverse effects in RA patients treated with sarilumab. Further research will be necessary to validate these findings, which may facilitate the establishment of clinically useful biomarkers to improve treatment personalization for patients with RA.
Sainz, L., Riera, P., Moya, P. And others. Effect of IL6R receptor genetic variants on treatment efficacy and toxicity response to sarilumab in rheumatoid arthritis. arthritis treatment 25, 226 (2023). https://doi.org/10.1186/s13075-023-03209-1
Sainz L, Riera P, Moya P, Bernal S, Casademont G, Diaz-Tornet C, Milan AM, Park HS, Lasa A, Corominas H. Role The 6R Genetic variants in predicting response to tocilizumab in patients with rheumatoid arthritis. Pharmaceuticals. 2022; 14(9):1942. https://doi.org/10.3390/الصيدلة14091942
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