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

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 join...

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Detalles Bibliográficos
Autores: Sainz, Luis|||0000-0001-9249-1983, Riera, Pau|||0000-0002-3074-3927, Moya, Patricia|||0000-0001-8339-5420, Bernal, Sara|||0000-0003-4427-0574, Casademont i Pou, Jordi|||0000-0002-8100-1827, Diaz-Torne, Cesar|||0000-0001-6275-7699, Millán, Ana Milena, Park, Hye S.|||0000-0002-4972-9527, Lasa, Adriana|||0000-0001-9957-9646, Corominas, Hèctor|||0000-0002-7738-6787
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:270867
Acceso en línea:https://ddd.uab.cat/record/270867
https://dx.doi.org/urn:doi:10.3390/jpm13010061
Access Level:acceso abierto
Palabra clave:IL6R
Genetic variants
Tocilizumab
Toxicity
Rheumatoid arthritis
Predictive biomarkers
Descripción
Sumario: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.

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