Clinical Value of IL6R Gene Variants as Predictive Biomarkers for Toxicity to Tocilizumab in Patients with Rheumatoid Arthritis


Por: Sainz L., Riera P., Moya P., Bernal S., Casademont J., Díaz-Torné C., Millán A.M., Park H.S., Lasa A., Corominas H.

Publicada: 1 ene 2023
Resumen:
Tocilizumab is a first-line biologic disease-modifying anti-rheumatic drug (bDMARD) that inhibits the interleukin-6 (IL-6) pathway by antagonizing the IL-6 receptor (IL-6R). Tocilizumab is widely used to treat rheumatoid arthritis (RA), a prevalent autoimmune disease that can cause irreversible joint damage and disability. Although many bDMARDs have been developed for RA, there is a lack of validated biomarkers which could guide personalized medicine strategies. To evaluate whether single-nucleotide polymorphisms (SNPs) in the IL6R gene could predict tocilizumab toxicity in patients with RA, we conducted a retrospective cohort study of 88 patients treated with tocilizumab. Six SNPs previously described in the IL6R gene were genotyped (rs12083537, rs11265618, rs4329505, rs2228145, rs4537545, and rs4845625). Using parametric tests, we studied the association between the SNPs and hepatotoxicity, infection, hypersensitivity, gastrointestinal, hematological, and dyslipidemia adverse events (AEs). We found associations between dyslipidemia and rs4845625 and between hematological AEs and rs11265618 and rs4329505. No further associations were found for the remaining SNPs and other AEs. Our findings support the potential clinical value of SNPs in the IL6R gene as predictive biomarkers for toxicity to tocilizumab in patients with RA.

Filiaciones:
Sainz L.:
 Hosp St Creu & St Pau HSCSP, Rheumatol Dept, Barcelona 08041, Spain

 Univ Autonoma Barcelona UAB, Fac Med, Barcelona 08041, Spain

 Inst Invest Biomed St Pau IIB SANT PAU, Barcelona 08041, Spain

Riera P.:
 Inst Invest Biomed St Pau IIB SANT PAU, Barcelona 08041, Spain

 Hosp Santa Creu & St Pau HSCSP, Pharm Dept, Barcelona 08025, Spain

 Inst Salud Carlos III, CIBER Enfermedades Raras CIBERER, Madrid 28029, Spain

Moya P.:
 Hosp St Creu & St Pau HSCSP, Rheumatol Dept, Barcelona 08041, Spain

 Inst Invest Biomed St Pau IIB SANT PAU, Barcelona 08041, Spain

Bernal S.:
 Inst Invest Biomed St Pau IIB SANT PAU, Barcelona 08041, Spain

 Inst Salud Carlos III, CIBER Enfermedades Raras CIBERER, Madrid 28029, Spain

 Hosp Santa Creu & St Pau HSCSP, Genet Dept, Barcelona 08025, Spain

Casademont J.:
 Univ Autonoma Barcelona UAB, Fac Med, Barcelona 08041, Spain

 Inst Invest Biomed St Pau IIB SANT PAU, Barcelona 08041, Spain

 Hosp Santa Creu & St Pau HSCSP, Med Dept, Barcelona 08025, Spain

Díaz-Torné C.:
 Hosp St Creu & St Pau HSCSP, Rheumatol Dept, Barcelona 08041, Spain

 Univ Autonoma Barcelona UAB, Fac Med, Barcelona 08041, Spain

 Inst Invest Biomed St Pau IIB SANT PAU, Barcelona 08041, Spain

Millán A.M.:
 Hosp St Creu & St Pau HSCSP, Rheumatol Dept, Barcelona 08041, Spain

 Inst Invest Biomed St Pau IIB SANT PAU, Barcelona 08041, Spain

Park H.S.:
 Hosp St Creu & St Pau HSCSP, Rheumatol Dept, Barcelona 08041, Spain

 Inst Invest Biomed St Pau IIB SANT PAU, Barcelona 08041, Spain

Lasa A.:
 Inst Invest Biomed St Pau IIB SANT PAU, Barcelona 08041, Spain

 Inst Salud Carlos III, CIBER Enfermedades Raras CIBERER, Madrid 28029, Spain

 Hosp Santa Creu & St Pau HSCSP, Genet Dept, Barcelona 08025, Spain

Corominas H.:
 Hosp St Creu & St Pau HSCSP, Rheumatol Dept, Barcelona 08041, Spain

 Univ Autonoma Barcelona UAB, Fac Med, Barcelona 08041, Spain

 Inst Invest Biomed St Pau IIB SANT PAU, Barcelona 08041, Spain
ISSN: 20754426
Editorial
MDPI, ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, Suiza
Tipo de documento: Article
Volumen: 13 Número: 1
Páginas:
WOS Id: 000915218200001
ID de PubMed: 36675722
imagen gold, Green Accepted, All Open Access, Gold, Green

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