Small Molecules

An Overview of Emerging Therapeutic Options in the Treatment of Psoriasis

Melinda Gooderham, MD, MSc, FRCPC


Skin Therapy Letter. 2013;18(7) 

In This Article


Psoriasis vulgaris is a chronic condition in which effective and safe therapies are needed for long-term use. To date, there have been promising results with small molecules for psoriasis including JAK inhibitors, PDE4 inhibitors, an S1P agonist, and DMF. The advantages of the small molecules are that they are amenable to both oral and topical use, do not require subcutaneous or parental administration, and avoid risk for immunogenicity. The mechanism of action of JAK inhibitors, PDE4 inhibitors and DMF provide downstream inhibition of the inflammatory cascade, resulting in blockade of multiple cytokines, which target cell types that are key players in psoriasis. The S1P agonists result in immunomodulation via sequestration of lymphocytes in lymphoid tissue. Time will tell whether any further new therapeutic targets are developed, such as TYK2, the final Janus kinase in the JAK family involved in cytokine signaling, which has not yet been investigated for psoriasis. TYK2 also appears to be a promising target as it associates with the receptors for IL-12/23 and IL-6, the major players in psoriasis pathogenesis. Another oral molecule to look out for is apilimod (STA-5326) (Synta Pharmaceuticals), which blocks the IL-12/23 pathway and has been studied in Phase 2 trials. Further investigations of these small molecules are warranted for both safety and efficacy, but we look forward to the possibility of new therapies as treatment options for our patients in the future.