Oral Roflumilast Suppresses Psoriatic Inflammation at the Gene and Cellular Level: Study

KEY TAKEAWAYS

• New research suggests oral roflumilast downregulated multiple proinflammatory cytokine genes in psoriatic lesions.
• Treatment reduced histologic infiltration of CD4⁺ T cells and neutrophils.
• Epidermal thickness decreased by 32% in the treatment group vs 7% with placebo.

In a mechanistic substudy of the PSORRO trial, oral roflumilast demonstrated targeted immunomodulatory effects in patients with moderate-to-severe plaque psoriasis.

Researchers for the vivo analysis sourght to characterize the drug’s impact on cellular and molecular pathways in psoriatic skin by analyzing biopsies from 24 patients enrolled in the 12-week, placebo-controlled trial. Biopsies were collected at baseline, week 4, and week 12. Participants were randomized (1:1) to receive either oral roflumilast 500 µg once daily or placebo.

According to the results, treatment with oral roflumilast was associated with a downregulation in gene expression of key proinflammatory cytokines, including CXCL1, CXCL8, IL1B, IL17A, IL23A, and IL36A, compared with placebo. Histologic analysis showed a reduction in immune cell infiltration, particularly CD4⁺ T cells and neutrophils. Epidermal thickness in lesional skin decreased by 32% from baseline in the treatment group vs 7% in the placebo group.

“Our findings suggest that oral roflumilast downregulates numerous key proinflammatory gene and histologic biomarkers, supporting its potential as a systemic treatment for psoriasis,” the authors wrote.

Source: Baez J, et al. Journal of Investigative Dermatology. 2025. Doi:10.1016/j.jid.2025.04.034