Researchers explored the potential of using a selective TYK2 inhibitor, BMS-986165, as a topical treatment for psoriasis—a novel approach compared to its recently approved oral formulation. Using a mouse model of imiquimod-induced psoriatic dermatitis, researchers applied a 1.5% BMS-986165 ointment to evaluate its therapeutic effects. The topical formulation significantly reduced psoriasis-like symptoms and inflammation. Single-cell RNA sequencing and flow cytometry revealed that keratinocytes —key skin cells in psoriasis—were major targets of the topical TYK2 inhibitor.

Further in vitro experiments showed that inhibiting TYK2 disrupted the AKT-SP1 signaling pathway, leading to decreased expression of the nerve growth factor receptor and reduced activation of AP1, a protein complex involved in proinflammatory signaling. These findings suggest that topical TYK2 inhibition directly reduces the inflammatory capabilities of keratinocytes, a key driver of psoriasis. This research highlights a promising new route for psoriasis treatment via topical TYK2 inhibition and uncovers a previously underexplored mechanism in keratinocyte-driven inflammation.

Reference: Fang Z, Jiang R, Wang Y, et al. Topical TYK2 inhibitor ameliorates psoriasis-like dermatitis via the AKT-SP1-NGFR-AP1 pathway in keratinocytes. Clin Transl Med. 2025 Mar;15(3):e70256. doi: 10.1002/ctm2.70256. PMID: 40038877; PMCID: PMC11879890.

This study investigated the underlying drivers of fatty liver disease (FLD) in patients with psoriasis, specifically examining whether insulin resistance (IR) or systemic inflammation is more closely associated. Using data from 647 individuals in the Shanghai Psoriasis Effectiveness Evaluation Cohort, researchers assessed IR through triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) indicators, while inflammation was measured using NLR, dNLR, and SII. The goal was to determine which of these factors more strongly correlates with FLD in the psoriasis population.

Results showed that markers of systemic inflammation were not significantly associated with FLD, while both TyG and TyG-BMI—particularly TyG-BMI—were consistently linked to the presence of FLD across various subgroups. These associations held even after excluding patients using medications like methotrexate and acitretin. Additionally, the diagnosis rate of metabolic-associated fatty liver disease (MAFLD) was significantly higher than that of NAFLD, suggesting that metabolic dysfunction, rather than inflammation, is the primary driver of FLD in psoriasis. As such, the study recommends using the term MAFLD for more accurate classification in this patient population.

Reference: Zhong X, Huang D, Chen R, et al. Positive association between insulin resistance and fatty liver disease in psoriasis: evidence from a cross-sectional study. Front Immunol. 2024 Apr 23;15:1388967. doi: 10.3389/fimmu.2024.1388967. PMID: 38715604; PMCID: PMC11074461.

A study revealed that women with psoriasis are significantly more likely than men to stop using biologic treatments, despite their known effectiveness. Biologics, which target specific immune pathways, are often considered the gold standard for moderate to severe psoriasis, yet nearly a third of patients discontinue them within a year. In an analysis of more than 1,000 patients, researchers found that only 42% of women continued biologic treatment for at least three years, compared to 57% of men. The gap was even larger with newer biologic classes, such as IL-17 and IL-23 inhibitors. Notably, women did not stop due to lack of efficacy—rather, they reported more side effects and lower satisfaction.

Adverse events such as gastrointestinal issues, headaches, and infections were reported nearly twice as often by women, though the actual incidence may not differ—women may simply be more likely to report symptoms. Even when side effects were absent, women still expressed lower satisfaction with biologics in areas like effectiveness, convenience, and overall experience. These findings underscore a broader issue: biologic treatment models have largely been developed with male participants in mind. To improve outcomes for women, researchers recommend more sex-specific studies and improved provider communication to set realistic expectations.

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Reference: Kassel G. Why Are More Women With Psoriasis Stopping Biologics? HealthCentral. Published June 27, 2025. Accessed July 10, 2025.