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Pharmacogenomics of Monoclonal Antibodies for the Treatment of Rheumatoid Arthritis.

ABSTRACT: Precision medicine refers to a highly individualized and personalized approach to patient care. Pharmacogenomics is the study of how an individual's genomic profile affects their drug response, enabling stable and effective drug selection, minimizing side effects, and maximizing therapeutic efficacy. Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in the joints. It mainly starts in peripheral joints, such as the hands and feet, and progresses to large joints, which causes joint deformation and bone damage due to inflammation of the synovial membrane. Here, we review various pharmacogenetic studies investigating the association between clinical response to monoclonal antibody therapy and their target genetic polymorphisms. Numerous papers have reported that some single nucleotide polymorphisms (SNPs) are related to the therapeutic response of several monoclonal antibody drugs including adalimumab, infliximab, rituximab, and tocilizumab, which target tumor necrosis factor (TNF), CD20 of B-cells, and interleukin (IL)-6. Additionally, there are some pharmacogenomic studies reporting on the association between the clinical response of monoclonal antibodies having various mechanisms, such as IL-1, IL-17, IL-23, granulocyte-macrophage colony-stimulating factor (GM-CSF) and the receptor activator of nuclear factor-kappa B (RANK) inhibition. Biological therapies are currently prescribed on a "trial and error" basis for RA patients. If appropriate drug treatment is not started early, joints may deform, and long-term treatment outcomes may worsen. Pharmacogenomic approaches that predict therapeutic responses for RA patients have the potential to significantly improve patient quality of life and reduce treatment costs.

SUBMITTER: Lim SH

PROVIDER: S-EPMC9410311 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Pharmacogenomics of Monoclonal Antibodies for the Treatment of Rheumatoid Arthritis.

Lim Sung Ho SH Kim Khangyoo K Choi Chang-Ik CI

Journal of personalized medicine 20220731 8

Precision medicine refers to a highly individualized and personalized approach to patient care. Pharmacogenomics is the study of how an individual's genomic profile affects their drug response, enabling stable and effective drug selection, minimizing side effects, and maximizing therapeutic efficacy. Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in the joints. It mainly starts in peripheral joints, such as the hands and feet, and progresses to large joints, ...[more]

PMID: 36013214

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Project description:In 15 patients with rheumatoid arthritis the baseline expression (t=0) of type I IFN-regulated genes was determined in peripheral blood cells (PAXgene) using cDNA-microarrays and compared to levels one month after (t=1) anti-TNF treatment (infliximab). Therefore, we used 43K cDNA microarrays from the Stanford Functional Genomics Facility (http://microarray.org/sfgf/) printed on aminosilane-coated slides containing ~20.000 unique genes. Only one batch of arrays was used for all experiments. First DNA spots were UV-cross linked to the slide using 150-300 mJoules. Sample preparation and microarray hybridization were performed as described previously (1,2). Data storage and filtering was performed using the Stanford Microarray Database (http://genome-www5.stanford.edu//) as described previously. 1. van der Pouw Kraan TC, Wijbrandts CA, van Baarsen LG, Voskuyl AE, Rustenburg F, Baggen JM et al.: Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients. Ann Rheum Dis 2007, 66: 1008-1014. 2. van der Pouw Kraan TC, van Baarsen LG, Rustenburg F, Baltus B, Fero M, Verweij CL: Gene expression profiling in rheumatology. Methods Mol Med 2007, 136: 305-327. Abbreviations: - Bnrs are the different patients analyzed - PAX or Paxgene indicates the total RNA was isolated from peripheral blood obtained in PAXgene tubes - CRS: common reference sample: We made a common reference that consisted of a mixture of mRNAs isolated from 11 different cell lines (Perou CM, Jeffrey SS, van de RM et al. Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc Natl Acad Sci U S A. 1999; 96:9212-9217) supplemented with RNA from rheumatoid synovial tissue, fibroblasts, and activated peripheral blood mononuclear cells (PBMCs). - PMT: photomultiplier tube: the sensitivity/intensity of the scanner can be adjusted to prevent spot saturation. Compound Based Treatment: anti-TNF (infliximab)

Dataset Information

Pharmacogenomics of Monoclonal Antibodies for the Treatment of Rheumatoid Arthritis.

Publications

Pharmacogenomics of Monoclonal Antibodies for the Treatment of Rheumatoid Arthritis.

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