Pharmacogenomics and the Resulting Impact on Psoriasis Therapies

Background: Psoriasis is characterized by multiple genetic variations. Some of these variations, such as the presence of HLA-Cw6 or TNFAIP3 single-nucleotide polymorphisms (SNPs), have been correlated to the response to biologic treatments. Objective: The aim of our study was to evaluate the effects of IL12B and IL6 SNPs on the response to ustekinumab. Methods: We retrospectively analyzed the genotypes of 64 patients who had been treated with ustekinumab for up to 1 year. Efficacy data were evaluated using ‘intention to treat-last observation carried forward' analysis. Results: We confirmed the positive role of HLA-Cw6 as a predictor of the response to ustekinumab and discovered that presence of the GG genotype on the IL12B rs6887695 SNP and absence of the AA genotype on the IL12B rs3212227 SNP significantly increase the probability of therapeutic success in HLA-Cw6 positive patients. Conclusions: The availability of pharmacogenetic data will influence therapeutic decisions in the clinical management of psoriatic patients.

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“…Only few pharmacogenetic studies have looked into the matter of biologic therapies in psoriasis [20,21,22,23,24,25]. …”

Section: Introductionmentioning

confidence: 99%

IL12B (p40) Gene Polymorphisms Contribute to Ustekinumab Response Prediction in Psoriasis

Galluzzo

Boca

Botti³

et al. 2015

Dermatology

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“…With the low doses used for psoriasis treatment, MTX plasma concentrations are too low to be measured, so drug monitoring cannot be used to predict the occurrence of adverse events. It has been therefore proposed that genetic polymorphisms should be investigated as predictors of response to treatment, either eicacy or toxicity [15][16][17].…”

Section: Low-dose Methotrexatementioning

confidence: 99%

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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“…Pharmacogenetic findings have potential to greatly impact clinical decisions. The advantages of such findings would include minimizing cost of treatment and improving treatment safety by minimizing adverse events [3].…”

Section: Introductionmentioning

confidence: 99%

“…As of recently, many other loci and polymorphisms are beginning to emerge as imparting some susceptibility to psoriasis as well. Pharmacogenetics is a term used to describe the study of the association between genetic polymorphisms and response to a drug [3]. Pharmacogenetic findings have potential to greatly impact clinical decisions.…”

Section: Introductionmentioning

confidence: 99%

“…The outcome and response to an individual has to a drug is due in part to many factors. These factors include the drug itself, the disease, and the individual, specifically his or her genes [3]. Psoriasis results from interactions of environmental and genetic factors, and as with many other autoimmune diseases, it is linked to polymorphisms within the HLA locus, particularly HLA-Cw0602 [1].…”

Section: Introductionmentioning

confidence: 99%

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Genetic Influences on Pharmacological Interventions in Psoriasis

Ahmed¹,

Yusuf²

2017

J Clin Exp Dermatol Res

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Psoriasis is a common chronic inflammatory disease that affects 2% of the population. Therapeutic intervention for psoriasis mainly targets inflammatory cascade through the use of topical agents, phototherapy, systemic agents and the newer biologic agents. The efficacy of many treatments used in psoriasis varies from patient to patient, and some of this variance in response can presumably be attributed to genetic differences. While current research findings are still limited, the clinical utilization of pharmacogenetics allows for tailored treatment plans that have the potential for better response amongst patients as well as conserving expenditures and healthcare resources. In this review, we hope to focus and summarize the conclusions and findings of studies done on the topic of pharmacogenetics in the treatment of psoriasis.

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Pharmacogenomics and the Resulting Impact on Psoriasis Therapies

Cited by 14 publications

References 60 publications

IL12B (p40) Gene Polymorphisms Contribute to Ustekinumab Response Prediction in Psoriasis

IL12B (p40) Gene Polymorphisms Contribute to Ustekinumab Response Prediction in Psoriasis

Pharmacogenetics of Psoriasis Treatment

Genetic Influences on Pharmacological Interventions in Psoriasis

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