Shrinking the Psoriasis Assessment Gap: Early Gene-Expression Profiling Accurately Predicts Response to Long-Term Treatment.
There is an "assessment gap" between the moment a patient's response to treatment is biologically determined and when a 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. Thanks to clinically accessible biopsy samples, high-quality molecular data for psoriasis patients are widely available. Psoriasis is therefore an excellent disease for testing the prospect of predicting treatment outcome from molecular data. Our study shows that gene-expression profiles of psoriasis skin lesions, taken in the first 4 weeks of treatment, can be used to accurately predict (>80% area under the receiver operating characteristic curve) the clinical endpoint at 12 weeks. This could decrease the psoriasis assessment gap by 2 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: one from detailed, platform-specific data and one from platform-independent, pathway-based data. We show that key biomarkers are associated with responses to drugs and doses and thus provide insight into the biology of pathogenesis reversion.
The Center for Clinical and Translational Science, The Rockefeller University, New York, New York, USA.
Joel
J
Correa da Rosa
The Center for Clinical and Translational Science, The Rockefeller University, New York, New York, USA; Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.
Jaehwan
J
Kim
Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin, China.
Suyan
S
Tian
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA; Department of Population Health Science and Policy, Icahn Institute for Genomics and Multiscale Biology, New York, New York, USA.
Lewis E
LE
Tomalin
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.
James G
JG
Krueger
The Center for Clinical and Translational Science, The Rockefeller University, New York, New York, USA; Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA; Department of Population Health Science and Policy, Icahn Institute for Genomics and Multiscale Biology, New York, New York, USA; Department of Genetics and Genomics Science, Icahn Institute for Genomics and Multiscale Biology, New York, New York, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: Mayte.SuarezFarinas@mssm.edu.
Mayte
M
Suárez-Fariñas
D015415:Biomarkers; D020869:Gene Expression Profiling; D006801:Humans; D011565:Psoriasis / Q000145:classification / Q000188:drug therapy* / Q000378:metabolism
D015415:Biomarkers