Impact of IL6R genetic variants on treatment efficacy and toxicity response to sarilumab in rheumatoid arthritis

• Published in: Arthritis research & therapy Vol. 25; no. 1; pp. 226 - 10
• Main Authors: Sainz, Luis, Riera, Pau, Moya, Patricia, Bernal, Sara, Casademont, Jordi, Díaz-Torné, Cesar, Millán, Ana Milena, Park, Hye Sang, Lasa, Adriana, Corominas, Hector
• Format: Journal Article
• Language: English
• Published: London BioMed Central 24.11.2023; BioMed Central Ltd; BMC
• Subjects: Analysis; Antirheumatic agents; Antirheumatic Agents - adverse effects; Arthritis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Biomarkers; Body mass index; Care and treatment; Diagnosis; Disease; Dosage and administration; Drugs; Genetic aspects; Genetic variants; Genetic variation; Health aspects; Hematology; Humans; IL6R; Medical records; Medicine; Medicine & Public Health; Metabolic disorders; Monoclonal antibodies; Orthopedics; Patients; Predictive factors; Proteins; Receptors, Interleukin-6 - genetics; Regulatory approval; Remission (Medicine); Response rates; Retrospective Studies; Rheumatoid arthritis; Rheumatology; Sarilumab; Single nucleotide polymorphisms; Toxicity; Treatment Outcome; Spain; United States > US; Predictive factors; Genetic variants; IL6R; Sarilumab; Rheumatoid arthritis
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-023-03209-1

Background Sarilumab, an IL-6 receptor antagonist, is a first-line biologic disease-modifying anti-rheumatic drug for rheumatoid arthritis. The identification of genetic biomarkers as predictors of response to sarilumab could allow for a personalized treatment strategy to improve clinical outcomes. Methods We conducted a retrospective cohort study of 62 patients treated with sarilumab to determine whether single-nucleotide polymorphisms (SNP) in the IL6R gene could predict efficacy and toxicity responses. Six SNPs previously described in the IL6R gene (rs12083537, rs11265618, rs4329505, rs2228145, rs4537545, and rs4845625) were genotyped in DNA samples obtained from these patients. Using parametric tests, we evaluated the association between these polymorphisms and clinicopathological features. Treatment response was assessed six months after treatment initiation. Satisfactory response was based on EULAR criteria. Low disease activity was determined according to DAS28 and CDAI and quantitative improvements in DAS28 and CDAI scores. Results Three SNPs (rs4845625, rs4329505 and rs11265618) were significantly associated with response outcomes. All of the SNPs, except for rs12083537, had at least one significant association with dyslipidemia or hepatotoxicity. Conclusions These findings support the potential clinical value of SNPs, particularly rs4845625, as potentially useful biomarkers to predict response to sarilumab in patients with RA.