Evidence map›Paper›PMID 41051639›Full record

ArticleAdvances in therapy2025

A Functional Genetic Score in the ZMIZ1/TGF-β/STAT Pathway Predicts Early Biologic Discontinuation in Psoriasis Patients Treated with Anti-TNF and Anti-IL12/23 Agents.

Juan de Luque, Carmen Mochón-Jiménez, Irene Rivera-Ruiz, Jesús Gay-Mimbrera, Judilyn Fuentes-Duculan, Israel Coats, Macarena Aguilar-Luque, Beatriz Isla-Tejera, Antonio Vélez-García Nieto, Manuel Galán-Gutiérrez and 4 more

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Advances in therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07041112 (Pharmacogenetic Observational Study Evaluating the Influence of Genetic Variants and Cardiometabolic Risk Factors on 10-Year Survival of Biologic Therapies in Patients With Cutaneous Psoriasis With or Without Psoriatic Arthritis), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07041112 completednot on this map

Pharmacogenetic Observational Study Evaluating the Influence of Genetic Variants and Cardiometabolic Risk Factors on 10-Year Survival of Biologic Therapies in Patients With Cutaneous Psoriasis With or Without Psoriatic Arthritis

TypeobservationalSponsorJuan Ruano RuizRan2012 to 2024Enrolled1,000ConditionsPsoriasis, Psoriatic Arthritis (PsA), Cardiovascular Risk Factors, Metabolic Syndrome (MetS)ArmsBiologic therapy for psoriasis
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Juan de LuqueInflammatory Immune-Mediated Chronic Skin Diseases Laboratory, IMIBIC, 14004, Córdoba, Spain.
Carmen Mochón-JiménezInflammatory Immune-Mediated Chronic Skin Diseases Laboratory, IMIBIC, 14004, Córdoba, Spain.
Irene Rivera-RuizInflammatory Immune-Mediated Chronic Skin Diseases Laboratory, IMIBIC, 14004, Córdoba, Spain.
Jesús Gay-MimbreraInflammatory Immune-Mediated Chronic Skin Diseases Laboratory, IMIBIC, 14004, Córdoba, Spain.
Judilyn Fuentes-DuculanLaboratory for Investigative Dermatology, Center for Clinical Translational Science, The Rockefeller University, New York, NY, 10065, USA.
Israel CoatsLaboratory for Investigative Dermatology, Center for Clinical Translational Science, The Rockefeller University, New York, NY, 10065, USA.
Macarena Aguilar-LuqueInflammatory Immune-Mediated Chronic Skin Diseases Laboratory, IMIBIC, 14004, Córdoba, Spain.
Beatriz Isla-TejeraInflammatory Immune-Mediated Chronic Skin Diseases Laboratory, IMIBIC, 14004, Córdoba, Spain.
Antonio Vélez-García NietoInflammatory Immune-Mediated Chronic Skin Diseases Laboratory, IMIBIC, 14004, Córdoba, Spain.
Manuel Galán-GutiérrezInflammatory Immune-Mediated Chronic Skin Diseases Laboratory, IMIBIC, 14004, Córdoba, Spain.
Teresa López-Viñau LópezInflammatory Immune-Mediated Chronic Skin Diseases Laboratory, IMIBIC, 14004, Córdoba, Spain. teresa.lopezvinau.sspa@juntadeandalucia.es.
Mayte Suarez-FariñasDepartment of Population Health Science and Policy, Center for Biostatistics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
James G KruegerLaboratory for Investigative Dermatology, Center for Clinical Translational Science, The Rockefeller University, New York, NY, 10065, USA.
Juan RuanoInflammatory Immune-Mediated Chronic Skin Diseases Laboratory, IMIBIC, 14004, Córdoba, Spain. juanruanoruiz@mac.com.ORCID http://orcid.org/0000-0002-0286-4107

Funding

Instituto de Salud Carlos III ICI1400136
6 · The paper itself

Abstract

introductionBiologic drug survival in psoriasis is variable. While clinical factors such as obesity and comorbidities contribute to early discontinuation, genetic predictors are less defined. The ZMIZ1/TGF-β/STAT axis regulates immune-metabolic responses and represents a promising pharmacogenetic target.

methodsWe retrospectively analyzed 875 biologic treatment courses from 312 patients with moderate-to-severe psoriasis (NCT07041112). A pathway-based genetic score was derived from seven single nucleotide polymorphisms (SNPs) in the ZMIZ1/TGF-β/STAT axis and dichotomized at the median. The primary outcome was time to biologic discontinuation, assessed with Kaplan-Meier curves and Cox proportional hazards models adjusted for demographic, clinical, and inflammatory covariates.

resultsPatients with a high genetic score had significantly longer drug survival (hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.62-0.89; p = 0.0015), despite elevated baseline tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-15, and leptin. This indicates that genetic background simultaneously conditioned immune-metabolic activation and treatment persistence. Predictive value was strongest for anti-IL12/23 agents (HR = 0.44; 95% CI: 0.26-0.75; p = 0.002) and anti-TNF therapies (HR = 0.79; 95% CI: 0.62-0.99; p = 0.045), but absent for anti-IL17/IL-23 agents after adjustment. None of the circulating biomarkers independently predicted survival.

conclusionA functional genetic score in the ZMIZ1/TGF-β/STAT pathway independently predicted long-term biologic persistence in psoriasis, particularly with anti-TNF and anti-IL12/23 therapies. Its association with immune-metabolic activation suggests that genetic background shapes both inflammatory status and treatment durability. Incorporating such profiling into predictive algorithms may improve treatment personalization and biologic retention.

trial registrationTrial Registration NCT07041112.

Indexed as

PsoriasisTranscription FactorsAdultFemaleHumansInterleukin-23MaleMiddle AgedPolymorphism, Single NucleotideRetrospective StudiesTransforming Growth Factor betaTumor Necrosis Factor-alphaInterleukin-23Transcription FactorsTransforming Growth Factor betaTumor Necrosis Factor-alphaBiologic therapyDrug survivalGenetic risk scorePharmacogeneticsPsoriasisSTAT pathwayTGF-βZMIZ1

Identifiers

PMID41051639

What Socratic holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.