A review of current therapeutics for psoriasis: Systemic and topical use of non-biological drugs.

purposePsoriasis is a chronic, immune-mediated inflammatory disease characterized by dysregulated cytokine signaling, keratinocyte hyperproliferation, and recurrent relapses requiring sustained management. Although biologic agents have transformed treatment by selectively targeting IL-17, IL-23, and TNF-α pathways, important limitations persist, including high costs, limited accessibility, treatment failures, and insufficient long-term safety data. Therefore, topical therapies and non-biologic small-molecule systemic agents remain essential, particularly for mild-to-moderate disease and for patients ineligible for biologic therapy. This review provides an integrative assessment of established and emerging topical and non-biologic systemic treatments.

methodsA systematic search of PubMed® and ClinicalTrials.gov with 'psoriasis, topical therapies, clinical trials, systemic therapy' keywords, identified several small-molecule classes in active clinical development, including JAK/TYK2 inhibitors, PDE-4 inhibitors, AhR modulators, A3AR agonists, RORγt and ROCK2 inhibitors, S1P1 modulators, and IRAK4/RIPK1 inhibitors.

resultsAmong these, oral TYK2 inhibitors have shown the most consistent late-phase success, offering superior PASI responses, rapid onset of action, and favorable emerging long-term safety profiles. Early-phase studies of other targets report promising reductions in inflammatory biomarkers and lesion severity, though interpretation remains limited by small cohorts, short follow-up, and the lack of head-to-head comparisons. Topical therapies, especially corticosteroids, remain foundational first-line options and valuable adjuncts to systemic regimens. While topical JAK inhibitors have generated interest in clinical trials, their clinical efficacy has not paralleled the superior outcomes achieved with oral JAK/TYK2 inhibitors.

conclusionOverall, current evidence suggests that targeted non-biologic small molecules are gaining importance as scalable, patient-friendly alternatives to biologics. Their optimal placement within future treatment algorithms will depend on long-term safety data, comparative clinical trials, biomarker-guided patient selection, and cost-effectiveness analyses.