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.
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.
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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
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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.
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