The Polymorphism Rs763780 in the
            <i>IL-17F</i>
            Gene is Associated with Response to Biological Drugs in Patients with Psoriasis

Prieto-Pérez, Rocío; Solano-López, G.; Cabaleiro, Teresa; Román, Manuel; Ochoa, Dolores; Talegón, María; Baniandrés, Ofelia; López-Estebaranz, J.L.; Cueva, Pablo de la; Daudén, E.; Abad‐Santos, Francisco

doi:10.2217/pgs.15.107

Cited by 49 publications

(60 citation statements)

References 41 publications

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“…IL-17F rs763780 was also investigated for the association with treatment outcome. This SNP was associated with no response to adalimumab after 6 months (TC genotype, p = 0.0044) and with beter response to inliximab after 3 and 6 months (TC genotype; p = 0.023 and p = 0.020, respectively) [56]. IL17RA rs4819554 polymorphism was associated with beter response after 12 weeks in carriers of AA genotype compared to AG and GG carriers (p = 0.03).…”

Section: Pharmacogenetics Of Anti-tnfα Treatmentmentioning

confidence: 96%

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 Treatmentmentioning

confidence: 96%

Pharmacogenetics of Psoriasis Treatment

Redenšek¹,

Dolžan²

2017

An Interdisciplinary Approach to Psoriasis

View full text Add to dashboard Cite

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“…IL-17, a previously mentioned interleukin involved in the Th17 pathways, was also studied for relevant polymorphisms. The IL-17F SNP rs763780 was associated with no response to adalimumab at weeks 24-28 (T/C genotype, P=0.0044) and a better response to infliximab at weeks 12-16 and 24-28 (T/C genotype, P=0.023 and P=0.020) [43]. Allele mutant C of SNP rs763680 was also associated with lower expression and activity of IL-17F, which may have influenced the interaction of IL-17F and its receptor [43].…”

Section: Il-12 and Il-23 Antagonistsmentioning

confidence: 99%

“…The IL-17F SNP rs763780 was associated with no response to adalimumab at weeks 24-28 (T/C genotype, P=0.0044) and a better response to infliximab at weeks 12-16 and 24-28 (T/C genotype, P=0.023 and P=0.020) [43]. Allele mutant C of SNP rs763680 was also associated with lower expression and activity of IL-17F, which may have influenced the interaction of IL-17F and its receptor [43]. IL-6 is a multifunctional cytokine which plays a vital role in signaling acute phase reactants and inflammation.…”

Section: Il-12 and Il-23 Antagonistsmentioning

confidence: 99%

“…Psoriasis patients with both HLA-Cw6 and rs1061622 G allele were at an increased risk for negative response to biologics, including ustekinumab [33]. Lastly, a study looked at SNPS in IL-17A and IL17F in regards to response to ustekinumab [43]. This study included controls (n=197) and individuals with moderate-to-severe psoriasis (n=194) and results of univariate analysis showed an association between IL-17F SNP rs763780 and response to ustekinumab (n=70) and 3 and 6 months [43].…”

Section: Il-12 and Il-23 Antagonistsmentioning

confidence: 99%

“…Lastly, a study looked at SNPS in IL-17A and IL17F in regards to response to ustekinumab [43]. This study included controls (n=197) and individuals with moderate-to-severe psoriasis (n=194) and results of univariate analysis showed an association between IL-17F SNP rs763780 and response to ustekinumab (n=70) and 3 and 6 months [43]. All results from the mentioned studies regarding anti-IL12/23 therapy and pharmacogenetics are summarized in Table 7.…”

Section: Il-12 and Il-23 Antagonistsmentioning

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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Predicting Clinical Responses to Ustekinumab

Blauvelt

2019

JAMA Dermatol

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In 2019, the efficacy and safety of biologic therapy offer most patients with psoriasis the opportunity to achieve safe and complete or nearly complete clearance of skin lesions. [1][2][3][4] A major obstacle remains across the world, however, in getting access to the best psoriasis medications, owing to high cost and/or lack of adequate health insurance. Indeed, it is commonplace for insurance companies and national regulatory authorities to control use of biologics to reduce overall costs to health care. More specifically, patients with psoriasis often have to experience treatment failure with cheaper, less effective, and less safe nonbiologic drugs prior to gaining access to biologics. 5 The use of older biologics, such as adalimumab and ustekinumab, is often required (because of their lower cost in some settings) prior to using newer biologics that target interleukin (IL)-17A or IL-23, 5 which are generally more effective. [1][2][3][4] Thus, the cost of health care often dictates therapeutic choices, rather than the physician and/or patient choosing what is best for the patient.Understanding which currently available medications will be most effective for treating a given patient with psoriasis is a practice gap for dermatologists, defining an opportunity for both personalized medicine and potential cost savings to the health care system by avoiding step therapy. While nonbiologic therapeutic options and older biologics for psoriasis are generally less effective than newer biologic options, subsets of patients do well with older therapies. [1][2][3][4] For example, 42.0% to 57.6% of patients with psoriasis taking ustekinumab achieve 90% improvement in their Psoriasis Area and Severity Index (PASI 90) at week 16. 1,2,4 If one could understand and predict which patient will respond to an older, cheaper biologic, such as ustekinumab, higher-cost alternatives could be avoided. In this issue of JAMA Dermatology, Tsakok et al 6 report that higher serum drug levels of ustekinumab soon after initiating therapy can predict whether a given patient will respond in the future to ustekinumab. Therapeutic drug monitoring (TDM) like that described in this article is available for ustekinumab 7 and adalimumab, 8 giving dermatologists tools that can help guide early decision-making on whether to keep treating a patient with a given biologic or to switch to another drug.In Great Britain, patients with psoriasis must cycle through methotrexate, cyclosporine, and phototherapy before being treated with a biologic. 5 After this, adalimumab and ustekinumab have been selected as first-line biologics (as designated in the National Health Service formulary), and must be used by patients prior to being treated with a newer more effective anti-IL-17A or anti-IL-23 biologic. [1][2][3][4][5] Tsakok et al 6 examined British patients with psoriasis who were enrolled in

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The Polymorphism Rs763780 in the IL-17F Gene is Associated with Response to Biological Drugs in Patients with Psoriasis

Cited by 49 publications

References 41 publications

Pharmacogenetics of Psoriasis Treatment

Pharmacogenetics of Psoriasis Treatment

Genetic Influences on Pharmacological Interventions in Psoriasis

Predicting Clinical Responses to Ustekinumab

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