7d8e5b475fb6cbfa5b0cc3976ba66a38 pmc_9865948.pdf 437d60fff57bc9e335dfe206b7d5cd48965b0749 pmc_9865948.pdf f8517eb9ab3cb9f2d72174920fe450de6960db21ce80b583457f7d8e19bc416c pmc_9865948.pdf Title: Clinical Value of IL6R Gene Variants as Predictive Biomarkers for Toxicity to Tocilizumab in Patients with Rheumatoid Arthritis Subject: 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. Keywords: IL6R; genetic variants; tocilizumab; toxicity; rheumatoid arthritis; predictive biomarkers Author: Luis Sainz, Pau Riera, Patricia Moya, Sara Bernal, Jordi Casademont, Cesar Díaz-Torné, Ana Milena Millán, Hye Sang Park, Adriana Lasa and Héctor Corominas Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Dec 28 07:25:04 2022 CET ModDate: Wed Dec 28 07:28:03 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 9 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 290281 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- IOJCNK+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 OWRGIF+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 QKRBCV+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 FNTSFI+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 ZNQLHG+URWPalladioL-BoldItal Type 1 Custom yes yes no 28 0 CYVJLM+VnURWPalladioL Type 1 Custom yes yes no 32 0 UIJACC+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 50 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 53 0 NJAOJC+CMSY10 Type 1 Builtin yes yes no 78 0 YSCNED+EURM10 Type 1 Builtin yes yes no 82 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-04 02:30:27 CEST RepresentationInformation: pmc_9865948.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-01-26 02:11:30 CET Size: 290281 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 244 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Study Population Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Genetic Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Patient Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Adverse Events Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Genetic Determinants and Adverse Events Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Info: Title: Clinical Value of IL6R Gene Variants as Predictive Biomarkers for Toxicity to Tocilizumab in Patients with Rheumatoid Arthritis Author: Luis Sainz, Pau Riera, Patricia Moya, Sara Bernal, Jordi Casademont, Cesar Díaz-Torné, Ana Milena Millán, Hye Sang Park, Adriana Lasa and Héctor Corominas Subject: 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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