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Berlin Brandenburg

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  • 1
    Language: English
    In: Pharmacogenomics, April 2014, Vol.15(6), pp.727-9
    Keywords: Clinical Translation ; Clinical Utility ; Cost–Effectiveness ; Evidence ; Pharmacogenetics ; Pharmacogenomics ; Prioritization ; Xxx ; Cost-Benefit Analysis -- Economics ; Drug Therapy -- Economics ; Pharmacogenetics -- Economics
    ISSN: 14622416
    E-ISSN: 1744-8042
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  • 2
    In: Pharmacogenomics, December 2013, Vol.14(16), p.2013-2021
    Description: Aims: This study aims to assess the cost–effectiveness in Australia of screening CYP2C19 loss-of-function (LoF) alleles to guide selection of clopidogrel or ticagrelor for individuals with acute coronary syndrome who are likely to undergo coronary stenting. Methods: Three treatment strategies were compared: universal clopidogrel therapy, universal ticagrelor therapy and genotyping CYP2C19 with use of ticagrelor for individuals with a LoF allele and clopidogrel for individuals without a LoF allele. Lifetime costs and quality-adjusted life years for each treatment strategy were estimated using a Markov model. The risks of events were primarily derived from the genetic substudy of the pivotal randomized controlled trial. Results: CYP2C19 genotyping resulted in greater effectiveness and was cost-effective when compared with universal use of clopidogrel. However, universal use of ticagrelor was the most effective strategy overall and the incremental cost–effectiveness compared with the genotyping strategy was generally within what is considered acceptable. Conclusion: Ticagrelor is likely to be cost-effective even for individuals not carrying a CYP2C19 LoF allele. ; Original submitted 30 May 2013; Revision submitted 16 August 2013
    Keywords: clopidogrel ; cost–effectiveness ; cytochrome P450 2C19 ; genotype ; pharmacogenetics
    ISSN: 1462-2416
    E-ISSN: 1744-8042
    Source: Future Science Group
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  • 3
    Language: English
    In: Pharmacogenomics, Sept, 2012, Vol.13(2), p.1427(8)
    Description: Aim: Leflunomide is a disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis. Not all patients respond to leflunomide and, as it has potentially serious side effects, targeting only those most likely to benefit would address a clinical need. We aimed to determine whether variations in the gene encoding DHODH, the molecular target of leflunomide, might include biomarkers that could be used to rationalize provision of this drug. Materials methods: We analyzed six haplotype-tagging SNPs in DHODH in 56 patients with rheumatoid arthritis treated with leflunomide. Clinical response was determined by assessing the change in 28 joint disease activity score over the first 3 months of treatment. Results conclusion: Carriage of a six-marker DHODH haplotype was associated with a reduced treatment response (p = 0.008). This suggests that a functional variant in strong linkage disequilibrium with this haplotype may predispose to reduced leflunomide efficacy. Original submitted 2 April 2012; Revision submitted 13 July 2012
    Keywords: Rheumatoid Arthritis -- Research ; Rheumatoid Arthritis -- Genetic Aspects ; Rheumatoid Arthritis -- Drug Therapy ; Leflunomide -- Dosage And Administration ; Leflunomide -- Research ; Oxidoreductases -- Genetic Aspects ; Oxidoreductases -- Research ; Single Nucleotide Polymorphisms -- Research
    ISSN: 1462-2416
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  • 4
    Language: English
    In: Pharmacogenomics, September 2012, Vol.13(12), pp.1427-34
    Description: Leflunomide is a disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis. Not all patients respond to leflunomide and, as it has potentially serious side effects, targeting only those most likely to benefit would address a clinical need. We aimed to determine whether variations in the gene encoding DHODH, the molecular target of leflunomide, might include biomarkers that could be used to rationalize provision of this drug. We analyzed six haplotype-tagging SNPs in DHODH in 56 patients with rheumatoid arthritis treated with leflunomide. Clinical response was determined by assessing the change in 28 joint disease activity score over the first 3 months of treatment. Carriage of a six-marker DHODH haplotype was associated with a reduced treatment response (p = 0.008). This suggests that a functional variant in strong linkage disequilibrium with this haplotype may predispose to reduced leflunomide efficacy.
    Keywords: Antirheumatic Agents -- Therapeutic Use ; Arthritis, Rheumatoid -- Drug Therapy ; Isoxazoles -- Therapeutic Use ; Oxidoreductases Acting on Ch-Ch Group Donors -- Genetics
    ISSN: 14622416
    E-ISSN: 1744-8042
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  • 5
    Language: English
    In: Pharmacogenomics, October 2016, Vol.17(15), pp.1725-1732
    Description: Oxaliplatin-based chemotherapy for colorectal cancer demonstrates interindividual variability in response, and polymorphisms of ERCC1, ERCC2, XRCC1, GSTP1 and GSTM1 genes may be contributing factors. Additionally, the effect of these genotypes may differ between ethnic groups. Material & Methods: A meta-analysis of the association between these genotypes and response, progression-free survival and overall survival (OS) for patients with colorectal cancer treated with oxaliplatin-based therapy is reported. Results: ERCC1 C118T (TT vs CC OS [hazard ratio (HR): 2.59; p = 0.001]), ERCC2 A2251C (CC or AC vs AA OS [HR: 1.53; p = 0.04]) and GSTP1 A313G (GG vs AA OS, [HR: 0.47; p 〈 0.001]) polymorphisms were associated with survival. The effect size may be larger for ERCC1 C118T and XRCC1 G1196A in Asian compared with Caucasian populations. No association was apparent for the GSTM1 genotype. ERCC1 C118T, ERCC2 A2251C and GSTP1 A313G polymorphisms were associated with clinical outcomes.
    Keywords: Ercc1 ; Ercc2 ; Gstm1 ; Gstp1 ; Xrcc1 ; Colorectal Neoplasm ; Meta-Analysis ; Oxaliplatin ; Pharmacogenetic ; Pharmacogenetics ; Antineoplastic Agents -- Therapeutic Use ; Colorectal Neoplasms -- Drug Therapy ; Organoplatinum Compounds -- Therapeutic Use
    ISSN: 14622416
    E-ISSN: 1744-8042
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  • 6
    Language: English
    In: Pharmacogenomics, December 2013, Vol.14(16), pp.2013-21
    Description: This study aims to assess the cost-effectiveness in Australia of screening CYP2C19 loss-of-function (LoF) alleles to guide selection of clopidogrel or ticagrelor for individuals with acute coronary syndrome who are likely to undergo coronary stenting. Three treatment strategies were compared: universal clopidogrel therapy, universal ticagrelor therapy and genotyping CYP2C19 with use of ticagrelor for individuals with a LoF allele and clopidogrel for individuals without a LoF allele. Lifetime costs and quality-adjusted life years for each treatment strategy were estimated using a Markov model. The risks of events were primarily derived from the genetic substudy of the pivotal randomized controlled trial. CYP2C19 genotyping resulted in greater effectiveness and was cost-effective when compared with universal use of clopidogrel. However, universal use of ticagrelor was the most effective strategy overall and the incremental cost-effectiveness compared with the genotyping strategy was generally within what is considered acceptable. Ticagrelor is likely to be cost-effective even for individuals not carrying a CYP2C19 LoF allele.
    Keywords: Acute Coronary Syndrome -- Drug Therapy ; Aryl Hydrocarbon Hydroxylases -- Genetics ; Cost-Benefit Analysis -- Economics
    ISSN: 14622416
    E-ISSN: 1744-8042
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