TNF-α −308 G/A polymorphism and responsiveness to TNF-α blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis

O’Rielly, Darren D.; Roslin, Nicole M.; Beyene, Joseph; Pope, Angela; Rahman, Proton

doi:10.1038/tpj.2009.7

Cited by 85 publications

(60 citation statements)

References 24 publications

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“…was associated with a poor response to the drug (p = 0.000245) [43]. This observation was in agreement with the indings of Mugnier et al that showed beter response to inliximab in RA patients with c.-308 GG genotype as compared to the patients with c.-308 AA/AG genotype [44].…”

Section: Pharmacogenetics Of Anti-tnfα Treatmentsupporting

confidence: 90%

Pharmacogenetics of Psoriasis Treatment

Redenšek¹,

Dolžan²

2017

An Interdisciplinary Approach to Psoriasis

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Psoriasis is a chronic systemic, immune-mediated disorder of unknown aetiology, usually presenting with typical inlammatory skin lesions and/or joint manifestations, but systemic inlammation that may lead to the development of co-morbidities may also be present. First-line therapy encompasses local cutaneous treatment and phototherapy, but with more severe symptoms or systemic course, systemic treatment with methotrexate (MTX), immunosuppressant cyclosporine, retinoid acitretin or biologicals may be used. Treatment response varies between patients in terms of eicacy and/or toxicity, which could, among other reasons, be due to genetic diferences between patients. Approximately 10-30% of patients experience adverse drug reactions with MTX treatment, leading to discontinuation of MTX mostly due to hepatotoxicity. Around 15% of patients experience adverse events when treated with biologicals; however, the most frequent reason for discontinuation is ineicacy or loss of the initially favourable response over time. Ineicacy or occurrence of adverse drug reactions cannot be predicted, so genetic biomarkers of drug response in combination with clinical data could be helpful in treatment planning. Several polymorphic genes have already been associated with treatment outcome, most of them involved in drug metabolism, transport and target pathways. Genetic biomarkers could be helpful in personalized care of psoriasis patients in order to prevent adverse events or predict ineicacy of a certain drug.

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Section: Pharmacogenetics Of Anti-tnfα Treatmentsupporting

confidence: 90%

Pharmacogenetics of Psoriasis Treatment

Redenšek¹,

Dolžan²

2017

An Interdisciplinary Approach to Psoriasis

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“…Since functional polymorphisms in genes of the OPG/RANKL/RANK pathway have been associated with osteoporosis and fractures in association studies as well as in genome-wide studies [1-3, 118, 119], their role in the pharmacogenetics of denosumab treatment has to be investigated. Indeed, in other conditions, gene polymorphisms have been shown to affect treatment regimens with human monoclonal antibodies, as in the case of the TNF-alpha-308(A) variant that predicts poor response to TNF-alpha blockers in rheumatoid arthritis [120].…”

Section: Other Pharmacogenomic Implications Of Antiresorptive and Anamentioning

confidence: 99%

Pharmacogenomics of Osteoporosis

Gennari

2010

Clinic Rev Bone Miner Metab

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Pharmacogenomics and pharmacogenetics are emerging interdisciplinary areas recently defined, respectively as ''the investigation of variations of DNA and RNA characteristics as related to drug response'', and the study of ''the influence of variations in DNA sequence on drug efficacy and toxicity''. A major challenge of future genetic studies in complex disorders such as osteoporosis is the development of specific genetic tests to identify responders from non-responders as well as to identify patients at higher risk to develop adverse reactions. Even though the knowledge of the genetic determinants of bone fragility and fracture risk has consistently increased over the past decade and despite the parallel development of multiple drugs with antiresorptive or anabolic activity in bone, there is still relatively little known about pharmacogenomics and pharmacogenetics of osteoporosis. This review provides an overview of available information and identifies potential targets for future studies in this field.

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“…163 A recent meta-analysis of nine studies representing a total of 692 RA patients, demonstrated that the probability of successful treatment with anti-TNF-α agents is influenced, at least in part, by the variant in the TNF-α gene promoter region. 164 The frequency of the TNF-α (-308A) variant was 22% in responders and 37% in nonresponders, and the OR was decreased in responders versus nonresponders (OR = 0.4, 95% CI: 0.4-0.7; P = 0.000245), irrespective of the TNF-α inhibitor prescribed. 164 This is strong evidence indicating that the TNF-α (-308A) variant predicts poor response to TNF-α inhibitors.…”

Section: Tnf-α Inhibitorsmentioning

confidence: 91%

“…164 The frequency of the TNF-α (-308A) variant was 22% in responders and 37% in nonresponders, and the OR was decreased in responders versus nonresponders (OR = 0.4, 95% CI: 0.4-0.7; P = 0.000245), irrespective of the TNF-α inhibitor prescribed. 164 This is strong evidence indicating that the TNF-α (-308A) variant predicts poor response to TNF-α inhibitors. The clinical utility of prospectively genotyping for this variant when initiating anti-TNF-α therapy for RA should now be formally assessed.…”

Section: Tnf-α Inhibitorsmentioning

confidence: 91%

Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies

O’Rielly

Rahman

2010

PGPM

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Rheumatoid arthritis (RA) is a chronic heterogeneous autoimmune disorder of unknown etiology resulting in inflammation in the synovium, cartilage, and bone. Genetic factors play an important role in susceptibility to RA as the heritability of RA is between 50% and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. Outside the major histocompatibility complex (MHC) region, six additional risk loci have been identified and validated including PTPN22, STAT4, PADI4, CTLA4, TNFAIP3-OLIG3, and TRAF1/C5. Genetic factors are also important in RA pharmacotherapy due to the gene-dependent activity of enzymes involved in the pharmacokinetics and/or pharmacodynamics of RA medications. Indeed, there is great variability in drug efficacy as well as adverse events associated with any anti-rheumatic therapy and genetics is thought to contribute significantly to this inter-individual variability in response. This review will summarize the genetic factors that have been implicated in the pathogenesis of RA, and how these determinants may factor into the potential pharmacogenetics of this disease. We will also review the therapeutic agents that are currently being utilized or presently being evaluated in the treatment of RA, along with potential pharmacogenetic markers that have been proposed for such medications.

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TNF-α −308 G/A polymorphism and responsiveness to TNF-α blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis

Cited by 85 publications

References 24 publications

Pharmacogenetics of Psoriasis Treatment

Pharmacogenetics of Psoriasis Treatment

Pharmacogenomics of Osteoporosis

Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies

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