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Shrinking the Psoriasis assessment gap: Early gene-expression profiling accurately predicts response to long-term treatment.

Shrinking the Psoriasis assessment gap: Early gene-expression profiling accurately predicts response to long-term treatment.
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Correa da Rosa J, Kim J, Tian S, Tomalin LE, Krueger JG, Suárez-Fariñas M,


Correa da Rosa J, Kim J, Tian S, Tomalin LE, Krueger JG, Suárez-Fariñas M, (click to view)

Correa da Rosa J, Kim J, Tian S, Tomalin LE, Krueger JG, Suárez-Fariñas M,

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The Journal of investigative dermatology 2016 9 22() pii S0022-202X(16)32457-5
Abstract

There is an ‘assessment gap’ between the moment patient treatment-response is biologically determined and when response can actually be determined clinically. Patients’ biochemical profiles are a major determinant of clinical outcome for a given treatment. It is therefore feasible that molecular-level patient information could be used to decrease the assessment gap. Due to clinically accessible biopsies, high-quality molecular data for psoriasis patients is widely available. Psoriasis is therefore an excellent disease for testing the prospect of predicting treatment outcome from molecular data. Our study demonstrates that gene-expression profiles of psoriasis skin lesions, taken in the first 4 weeks of treatment, can be used to accurately predict (>80% AUC) clinical end-point at 12 weeks. This could decrease the psoriasis assessment gap by two months. We present two distinct prediction modes: a universal predictor, aimed at forecasting the efficacy of untested drugs, and specific predictors aimed at forecasting clinical response to treatment with four specific drugs: Etanercept, Ustekinumab, Adalimumab and Methotrexate. We also develop two forms of prediction: from detailed, platform-specific data, as well as platform-independent pathway-based data. We demonstrate that key biomarkers are associated with responses to novel drugs and doses, and thus provide insight into the biology of pathogenesis reversion.

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