Analysis of associations between polymorphisms within genes coding for tumour necrosis factor (TNF)-alpha and TNF receptors and responsiveness to TNF-alpha blockers in patients with rheumatoid arthritis

Świerkot, Jerzy; Bogunia‐Kubik, Katarzyna; Nowak, Beata; Białowąs, Katarzyna; Korman, Lucyna; Gębura, Katarzyna; Kolossa, Katarzyna; Jeka, Sławomir; Wiland, Piotr

doi:10.1016/j.jbspin.2014.08.006

Cited by 47 publications

(46 citation statements)

References 30 publications

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“…For this reason, RF and anti‐CCP may be useful as predictors of response to tocilizumab and rituximab. Similarly, genetic factors also play an essential role in interindividual differences in response to biological therapies . Clinical, biochemical, and genetic parameters may thus be a useful tool for guiding treatment selection.…”

Section: Discussionmentioning

confidence: 99%

FCGR2A/FCGR3A Gene Polymorphisms and Clinical Variables as Predictors of Response to Tocilizumab and Rituximab in Patients With Rheumatoid Arthritis

Morales

Maldonado-Montoro

Plata

et al. 2018

The Journal of Clinical Pharma

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We evaluated the influence of clinical, biochemical, and genetic factors on response in 142 patients diagnosed with rheumatoid arthritis, of whom 87 patients were treated with tocilizumab (61.26%) and 55 patients were treated with rituximab (38.7%;) according to the variables European League Against Rheumatism (EULAR) response, remission, low disease activity, and improvement in Disease Activity Score, 28 joints (DAS28) at 6, 12, and 18 months. A retrospective prospective cohort study was conducted. Patients carrying the FCGR3A rs396991‐TT genotype treated with tocilizumab showed higher EULAR response (OR, 5.075; 95%CI, 1.20–21.33; P = .027) at 12 months, those who were naive for biological disease‐modifying antirheumatic drugs (bDMARDs) at the beginning of treatment showed satisfactory EULAR response, higher remission, and greater improvement in DAS28 at 6 months. Younger age at start of tocilizumab treatment was associated with satisfactory EULAR response at 18 months and greater remission at 6 and 18 months. Subcutaneous tocilizumab administration was associated with higher remission at 6 months and improved low disease activity rate at 12 months. In patients treated with rituximab, carriers of the FCGR2A rs1801274‐TT genotype had higher EULAR response at 6 months (OR, 4.861; 95%CI, 1.11–21.12; P = .035), 12 months (OR, 4.667; p = 0.066, 95%CI, 0.90–24.12; P = .066), and 18 months (OR, 2.487; 95%CI, 0.35–17.31; P = .357), higher remission (OR: 10.625; p = 0.044, CI95%: 1.07, 105.47) at 6 months, and greater improvement in DAS28 at 12 months (B = 0.782; 95%CI, −0.15 to 1.71; P = .098) and 18 months (B = 1.414; 95%CI, 0.19–2.63; P = .025). The FCGR3A rs396991‐G allele was associated with improved low disease activity rate (OR, 4.904; 95%CI, 0.84–28.48; P = .077) and greater improvement in DAS28 (B = −1.083; 95%CI, −1.98 to −0.18; P = .021) at 18 months. Patients with a lower number of previous biological therapies had higher remission at 12 months. We suggest that the FCGR3A rs396991‐TT genotype, higher baseline value of DAS28, subcutaneous tocilizumab administration, younger age at the beginning of treatment, and being bDMARD naive are associated with better response to tocilizumab. In patients treated with rituximab, we found better response in those patients with the FCGR2A rs1801274‐TT genotype, the FCGR3A rs396991‐G allele, and lower number of previous biological therapies.

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Section: Discussionmentioning

confidence: 99%

FCGR2A/FCGR3A Gene Polymorphisms and Clinical Variables as Predictors of Response to Tocilizumab and Rituximab in Patients With Rheumatoid Arthritis

Morales

Maldonado-Montoro

Plata

et al. 2018

The Journal of Clinical Pharma

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“…Our former studies showed that genetic variability within genes coding for pro-inflammatory cytokines (Bogunia-Kubik et al 2015; Świerkot et al 2015) may play a role in RA development and response to treatment with TNF-α inhibitors (TNFi). It has been also documented that acting through NF-κB pathway, some miRNAs such as miR-146a and miR-155 may stimulate the release of pro-inflammatory cytokines.…”

Section: Introductionmentioning

confidence: 99%

Significance of Polymorphism and Expression of miR-146a and NFkB1 Genetic Variants in Patients with Rheumatoid Arthritis

Bogunia‐Kubik

Wysoczańska

Piątek

et al. 2016

Arch. Immunol. Ther. Exp.

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MicroRNA-146a (miR-146a) has been shown to play an important role in the regulation of inflammatory innate immune responses, and found to be differentially expressed in rheumatoid arthritis (RA). Through NF-κB pathway, this molecule is able to stimulate the release of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-17. It has been also suggested that single-nucleotide polymorphisms (SNPs) in miRNA sequences may alter miRNA expression and that miR-146a rs2910164 SNP may contribute to RA development. These observations prompted us to analyze the potential associations between the miR-146a-3p (rs2910164, G > C) and NFkB1 (rs28362491, ins/del ATTG) polymorphisms and miR-146a-5p expression in patients’ sera in relation to clinical outcome of the treatment as well as predisposition to RA. Genotyping was performed in 111 patients and 130 healthy individuals while 16 controls and 13 RA patients (before and after three months of therapy with TNF-α inhibitors (TNFi)) were studied for the circulating miR-146a-5p serum expression level. Patients carrying the NFkB1 ins/ins genotype were characterized by worse response to TNFi treatment (p = 0.023). In patients, before TNFi therapy, expression levels of miR-146a-5p were less (0.422 ± 0.171) as compared to those detected after three months of treatment (1.809 ± 0.658, p = 0.033) and observed for healthy controls (5.302 ± 2.112, p = 0.048). Moreover, patients with higher circulating miR-146a-5p levels after three months of TNFi administration were more frequently carrying the rs2910164-C allele (p = 0.032). These results support the hypothesis that miR-146a might be involved in pathogenesis of RA and imply that miR-146a-3p polymorphism may be associated with miR-146a-5p levels in serum after anti-TNF-α treatment.

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“…Regarding the TNFA polymorphisms at position 857, RA patients with the T allele of TNFA‐857 CT SNP (rs1799724) respond better to etanercept therapy than homozygotes for the C allele and other TNF‐blockers . Miceli‐Richard et al showed that TNF locus haplotype (−238G/−308G/−857C) in a homozygous form is associated with a lower response to adalimumab (specifically in those treated with adalimumab and MTX).…”

Section: Current Knowledge About Pharmacogenetics Of Adsmentioning

confidence: 99%

“…Miceli‐Richard et al showed that TNF locus haplotype (−238G/−308G/−857C) in a homozygous form is associated with a lower response to adalimumab (specifically in those treated with adalimumab and MTX). Determination of 5 SNPs in the TNF‐α (TNFA G‐308A [rs1800629], TNFA G‐238A [rs3615525], TNFA C‐857T [rs1799724]) and TNF receptor (TNFR1A G36A [rs767455], TNFR1B T676G, [rs1061622]) in RA patients showed association of homozygosity for the TNFR1A 36A allele and the TNFA‐875T (rs1799724) variant with a better response to anti‐TNF treatment . Lack of association of TNF‐α‐308 GA (rs1800629) and disease activity or response to etanercept therapy has been reported; however, a combined IL‐6/TNF‐α genotype was found to be a predictor of response to etanercept .…”

Section: Current Knowledge About Pharmacogenetics Of Adsmentioning

confidence: 99%

Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases

2018

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For many years, a considerable number of patients with autoimmune diseases (ADs) have suffered from a lack of drug response and drug-related toxicity. Despite the emergence of new therapeutic options such as biological agents, patients continue to struggle with these problems. Unfortunately, new challenges, including the paradoxical effects of biological drugs, have complicated the situation. In recent decades, efforts have been made to predict drug response as well as drug-related side effects. Thanks to the many advances in genetics, evaluation of markers to predict drug response/toxicity before the initiation of treatment may be an avenue toward personalizing treatments. Implementing pharmacogenetics and pharmacogenomics in the clinic could improve clinical care; however, obstacles remain to effective personalized medicine for ADs. The present study attempted to clarify the concept of pharmacogenetics/pharmacogenomics for ADs. After an overview on the pathogenesis of the most common types of treatments, this paper focuses on pharmacogenetic studies related to the selected ADs. Bridging the gap between pharmacogenetics and personalized medicine is also discussed. Moreover, the advantages, disadvantages and recommendations related to making personalized medicine practical for ADs have been addressed.

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Analysis of associations between polymorphisms within genes coding for tumour necrosis factor (TNF)-alpha and TNF receptors and responsiveness to TNF-alpha blockers in patients with rheumatoid arthritis

Cited by 47 publications

References 30 publications

FCGR2A/FCGR3A Gene Polymorphisms and Clinical Variables as Predictors of Response to Tocilizumab and Rituximab in Patients With Rheumatoid Arthritis

FCGR2A/FCGR3A Gene Polymorphisms and Clinical Variables as Predictors of Response to Tocilizumab and Rituximab in Patients With Rheumatoid Arthritis

Significance of Polymorphism and Expression of miR-146a and NFkB1 Genetic Variants in Patients with Rheumatoid Arthritis

Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases

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