Association of the Psoriatic Microenvironment With Treatment Response.
Importance: The ability to predict the efficacy of systemic psoriasis therapy based on immune profiles in skin biopsies could reduce the use of inappropriate treatment and its associated costs and adverse events. It could considerably decrease drug development trial costs as well.Objective: To devel...
| Publicado en: | JAMA Dermatology Vol. 156; no. 10; pp. 1057 - 1066 |
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| Autores principales: | , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
American Medical Association
Oct2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=146463239&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 146463239 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 21686068 FTFQ jtl: JAMA Dermatology issn: 21686068 maglogo: N pubinfo: dt: Oct2020 vid: 156 iid: 10 pid: 30 pub: American Medical Association place: Chicago, Illinois artinfo: ui: 146463239 146463239 NLM32876657 146463239 10.1001/jamadermatol.2020.2118 NLM32876657 146463239 ppf: 1057 ppct: 9 formats: tig: atl: Association of the Psoriatic Microenvironment With Treatment Response. aug: au: Wang, Gaofeng Miao, Yong Kim, Noori Sweren, Evan Kang, Sewon Hu, Zhiqi Garza, Luis A. affil: Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, China sug: subj: Biological Factors Administration and Dosage Psoriasis Drug Therapy Gene Expression Profiling Psoriasis Immunology Heterocyclic Compounds Administration and Dosage Skin Psoriasis Diagnosis Treatment Outcomes Severity of Illness Indices Methotrexate Administration and Dosage Skin Drug Effects Biopsy Gene Expression Profiling Methods Skin Pathology Prognosis RNA Metabolism Psoriasis Piperidines Administration and Dosage Retrospective Design Data Collection Funding Source Questionnaires Human ab: Importance: The ability to predict the efficacy of systemic psoriasis therapy based on immune profiles in skin biopsies could reduce the use of inappropriate treatment and its associated costs and adverse events. It could considerably decrease drug development trial costs as well.Objective: To develop a bioinformatic gene signature score derived from skin mRNA to predict psoriasis treatment outcomes for a variety of therapies.Design, Setting, and Participants: In this decision analytical model using 1145 skin samples from different cohorts of 12 retrospective psoriasis studies, samples were analyzed using the CIBERSORT algorithm to define the immune landscape of psoriasis lesions and controls. Random forest classification and principal component analysis algorithms were used to estimate psoriatic microenvironment (PME) signature genes and construct a PME score. Overall, 85 and 421 psoriasis lesions from 1 and 4 independent cohorts were used as discovery and validation studies, respectively. Among them, 157, 71, 89, and 90 psoriasis lesions were treated with etanercept, tofacitinib, adalimumab, and methotrexate, respectively.Main Outcomes and Measures: Number of weeks after treatment initiation when responders and nonresponders could be predicted.Results: Overall, 22 immune cell subtypes formed infiltration patterns that differentiated psoriasis lesions from healthy skin. In psoriasis lesions, the expression of 33 PME signature genes defined 2 immune phenotypes and in aggregate could be simplified to a numerical PME score. A high PME score, characterized by keratinocyte differentiation, correlated with a better treatment response (Psoriasis Area and Severity Index [PASI] reduction, 75.8%; 95% CI, 69.4% to 82.2%; P = .03), whereas a low PME score exhibited an immune activation signature and was associated with a worse response (PASI reduction, 53.5%; 95% CI, 45.3% to 61.7%; P = .03). The PME score at week 4 after treatment initiation correlated with future responder vs nonresponder to treatment status 8 to 12 weeks earlier than PASI reduction for etanercept, methotrexate plus adalimumab, and tofacitinib.Conclusions and Relevance: The PME score is a biometric score that may predict clinical efficacy of systemic psoriasis therapy in advance of clinical responses. As an application of personalized medicine, it may reduce the exposure of patients with psoriasis to ineffective and expensive therapies. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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