Therapeutic Advances in Psoriasis: From Biologics to Emerging Oral Small Molecules

Abstract

Psoriasis is a persistent, inflammatory condition affecting millions globally, marked by excessive keratinocyte proliferation, immune cell infiltration, and widespread inflammation. Over the years, therapeutic approaches have developed significantly, shifting from conventional topical treatments and phototherapy to more sophisticated systemic interventions such as biologics and, recently, oral small-molecule drugs. This review seeks to present a comprehensive investigation of the existing psoriasis treatment options, focusing on biologic agents, oral small molecules, and emerging treatments. Several categories of biologic treatments have received regulatory approval for psoriasis, including TNF-α, IL-17, IL-12/23, and IL-23 inhibitors. Biologics have revolutionized the treatment of psoriasis. These targeted therapies offer significant improvement in disease control and quality of life, with acceptable safety profiles. However, limitations such as cost, potential immunogenicity, and administration challenges have driven the exploration of alternative treatment modalities. Oral small molecules, particularly inhibitors of Janus kinase (JAK), have emerged as options due to their convenience and efficacy. These agents represent a paradigm shift in the management of the condition, offering oral administration and targeted action on specific signaling pathways. In addition to existing therapies, the review explores emerging treatments that hold promise for the future of psoriasis care. These include innovative small-molecule inhibitors. Early-stage clinical trials suggest these agents may enhance outcomes for psoriasis patients. In conclusion, the therapeutic landscape of psoriasis is rapidly evolving, emphasizing targeted, patient-centered treatments. Ongoing research and development are expected to lead to more personalized and effective management strategies for this complex condition.

Keywords: IL-17; IL-23; JAK/STAT; inhibitors; plaque psoriasis; psoriasis.

Figure 1

The interplay of cytokine pathways in psoriasis. A sophisticated web connects the fundamental molecules involved in the development of psoriasis. This interconnection is regarded as pivotal for advancement. On one front, the reciprocal enhancement of the adaptive and innate immune systems generates multiple cytokines and sustains characteristic psoriatic traits in both the dermis and epidermis. Conversely, keratinocytes foster the mediators and bolster the proliferation of activation.

Figure 2

A schematic figure of the JAK/STAT pathway illustrating the mechanism of action of JAK inhibitors. P is the chemical symbol for phosphorus.