Key Advances in Oral Therapies for Psoriasis Unveiled at Winter Clinical Dermatology Conference 2025

April W. Armstrong, MD, MPH

Photo courtesy of dermsquared

At the 2025 Midwinter Clinical Hawaii Dermatology Conference being held in Hawaii, April W. Armstrong MD, MPH, professor and chief of the Division of Dermatology at the University of California Los Angeles, presented significant late-breaking updates in oral therapies for psoriasis. The presentation highlighted new treatment approaches, including FDA-approved agents and investigational therapies, with a focus on improving patient outcomes through targeted mechanisms.

Apremilast: A Staple for Mild to Moderate Psoriasis

Apremilast, an oral phosphodiesterase-4 (PDE4) inhibitor, continues to demonstrate efficacy in treating mild-to-moderate plaque psoriasis, particularly in patients unresponsive to topical therapy. In the phase 3 ADVANCE clinical trial, researchers reported that 21% of bio-naïve patients achieved a static Physician’s Global Assessment (sPGA) score of 0 or 1 with a ≥2-point improvement over 16 weeks. The drug remains a critical option, especially for patients with a history of malignancy or those who cannot tolerate systemic immunosuppressants.

Targeting TYK2: Deucravacitinib’s Superiority Over Apremilast

Armstrong emphasized the role of tyrosine kinase 2 (TYK2) inhibition in psoriasis treatment, particularly through deucravacitinib, a selective TYK2 inhibitor.

“TYK2 is important because it’s an intracellular molecule that helps to transmit the signal of IL-23, which is critical to psoriasis pathogenesis,” Armstrong explained. “We have an FDA-approved therapy, deucravacitinib, which inhibits the regulatory domain of the TYK2 molecule.”

Data from the POETYK PSO-1 and PSO-2 trials showed that deucravacitinib provided superior efficacy compared to both placebo and apremilast. At week 16, 53.6% and 58.4% of patients receiving deucravacitinib achieved sPGA 0/1, significantly higher than apremilast (32.1% and 31.0%, respectively, P < .0001). Additionally, deucravacitinib demonstrated notable efficacy in treating psoriasis in special areas, including the scalp, nails, and palmoplantar regions.

“Which patients are right for deucravacitinib? We know it is approved for moderate-to-severe plaque psoriasis, but I think the sweet spot for this oral medication is someone who is systemic-naïve and their severity is more on the moderate end of the spectrum,” Armstrong stated. “The reason being is that deucravacitinib is likely able to bring those patients to clear or almost clear.”

Emerging Oral Therapies

Looking ahead, novel agents targeting the IL-23/IL-17 pathway and TYK2 inhibition are poised to reshape the treatment landscape. JNJ-77242114, an IL-23 receptor blocker, showed promising results in the FRONTIER 2 study, with PASI 75 and PASI 90 response rates exceeding 65% and 50%, respectively, at week 52.

Meanwhile, second-generation TYK2 inhibitors, such as zasocitinib (TAK-279) and ESK-001, offer increased specificity, reducing the potential for off-target JAK inhibition. Phase 2b trials of zasocitinib revealed significant PASI 75, 90, and 100 response rates, reinforcing its potential as a next-generation oral therapy.

“We also have oral tumor necrosis factor (TNF) inhibitors in development as well, where this molecule interacts with soluble TNF alpha (TNF-α) and distorts the cytokine so it cannot bind to the receptor,” Armstrong added.