Impact of IL6R genetic variants on treatment efficacy and toxicity response to sarilumab in rheumatoid arthritis
Por:
Sainz, L, Riera, P, Moya, P, Bernal, S, Casademont, J, Diaz-Torne, C, Millan, AM, Park, HS, Lasa, A, Corominas, H
Publicada:
24 nov 2023
Resumen:
BackgroundSarilumab, 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.MethodsWe 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.ResultsThree 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.ConclusionsThese findings support the potential clinical value of SNPs, particularly rs4845625, as potentially useful biomarkers to predict response to sarilumab in patients with RA.
Filiaciones:
Sainz, L:
Hosp Santa Creu I Santa Pau, Rheumatol Dept, Barcelona, Spain
Univ Autonoma Barcelona UAB, Dept Med, Barcelona, Spain
Inst Invest Biomed St Pau IIB Sant Pau, Barcelona, Spain
Riera, P:
Inst Invest Biomed St Pau IIB Sant Pau, Barcelona, Spain
Hosp Santa Creu i Santa Pau, Pharm Dept, Barcelona, Spain
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Moya, P:
Hosp Santa Creu I Santa Pau, Rheumatol Dept, Barcelona, Spain
Inst Invest Biomed St Pau IIB Sant Pau, Barcelona, Spain
Bernal, S:
Inst Invest Biomed St Pau IIB Sant Pau, Barcelona, Spain
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Hosp Santa Creu I Santa Pau, Inst Invest Biomed St Pau, Genet Dept, Barcelona, Spain
Casademont, J:
Univ Autonoma Barcelona UAB, Dept Med, Barcelona, Spain
Inst Invest Biomed St Pau IIB Sant Pau, Barcelona, Spain
Hosp Santa Creu I Santa Pau, Internal Med Dept, Barcelona, Spain
Diaz-Torne, C:
Hosp Santa Creu I Santa Pau, Rheumatol Dept, Barcelona, Spain
Univ Autonoma Barcelona UAB, Dept Med, Barcelona, Spain
Inst Invest Biomed St Pau IIB Sant Pau, Barcelona, Spain
Millan, AM:
Hosp Santa Creu I Santa Pau, Rheumatol Dept, Barcelona, Spain
Park, HS:
Hosp Santa Creu I Santa Pau, Rheumatol Dept, Barcelona, Spain
Lasa, A:
Inst Invest Biomed St Pau IIB Sant Pau, Barcelona, Spain
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Hosp Santa Creu I Santa Pau, Inst Invest Biomed St Pau, Genet Dept, Barcelona, Spain
Corominas, H:
Hosp Santa Creu I Santa Pau, Rheumatol Dept, Barcelona, Spain
Univ Autonoma Barcelona UAB, Dept Med, Barcelona, Spain
Inst Invest Biomed St Pau IIB Sant Pau, Barcelona, Spain
gold, All Open Access; Gold Open Access; Green Open Access
|