Pharmacogenetics of psoriasis:HLA-Cw6but notLCE3B/3Cdeletion norTNFAIP3polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab

Talamonti, Mark S.; Botti, Elisabetta; Galluzzo, Marco; Teoli, Miriam; Spallone, Giulia; Bavetta, Mauro; Chimenti, Sergio; Costanzo, Antonio

doi:10.1111/bjd.12331

Cited by 138 publications

(141 citation statements)

References 20 publications

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“…46 In the present study, some of the patients were included in both the ustekinumab cohort and the anti-TNF cohort; however, as the treatments target different pathways, including previously treated patients is a commonly used approach. [47][48][49][50] Efficacy of treatments was evaluated based on both drug survival of 6 months and relative PASI reduction after 3 months. We cannot exclude that categorization of response for some of the patients may be influenced by other factors, for example, comedication, patients' preferences or dose changes, although this is highly unlikely as these factors primarily affect the overall long-term drug survival and not the short-term response.…”

Section: Study Populationmentioning

confidence: 99%

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

et al. 2017

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Section: Study Populationmentioning

confidence: 99%

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

et al. 2017

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“…Polymorphisms in this gene have been linked to varying responses to psoriasis treatments. HLA-Cw6 positive patients were found to have poor response to TNF-alpha inhibitors [30] and HLACw6 negative patients were reported as having a higher (but not statistically significant) response to TNF-alpha inhibitors [37]. However, a more recent study conflicts these findings and showed a trend toward better response amongst HLA-Cw6 positive patients and TNF-alpha inhibitors [38].…”

Section: Hla Related Findingsmentioning

confidence: 94%

“…[37] HLA-C *06:02 Human Leukocyte Antigen encodes for the major histocompatibility (MHC) complex responsible for immune reactions.…”

Section: Hla-cw6mentioning

confidence: 99%

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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“…A cohort of 51 patients with psoriasis treated with ustekinumab was tested for three polymorphisms, including the HLA-Cw6 positivity, TNFAIP3 rs610604 polymorphism and LCE3B/3C gene deletions. Beter and faster response to ustekinumab was observed in HLA-Cw6 positive patients, while no signiicant association with response was observed for the other two investigated genes [68]. Another larger study conirmed the role of HLA-Cw6 as Chui et al reported that HLA-Cw6 positive patients were more likely to achieve PASI50, 75 and 90 after 28 weeks of treatment [69].…”

Section: Il12/23 Inhibitorsmentioning

confidence: 94%

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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Pharmacogenetics of psoriasis:HLA-Cw6but notLCE3B/3Cdeletion norTNFAIP3polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab

Abstract: Our observations underline the role of HLA-Cw6 not only as a psoriasis susceptibility gene, but also as a pharmacogenetic marker of response to ustekinumab in psoriasis.

Cited by 138 publications

References 20 publications

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

Genetic Influences on Pharmacological Interventions in Psoriasis

Pharmacogenetics of Psoriasis Treatment

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