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

Sphingosine 1-Phosphate Receptor Agonists

Sphingosine 1-phosphate (S1P) is a sphingolipid required by lymphocytes to exit the lymphoid tissue and enter the bloodstream via a chemotactic gradient.[24] Agonists of the S1P receptor cause a blockade of lymphocyte migration out of the lymph tissue through internalization of the receptor, resulting in a sequestration of lymphocytes. Recent development of S1P agonists involve utilizing these agents in the treatment of lymphocyte-mediated autoimmune conditions such as multiple sclerosis. Most recently, a drug from this class, fingolimod, was approved for the treatment of multiple sclerosis.[25]


The S1P1 agonist, ponesimod, has been studied in psoriasis vulgaris in a Phase 2, randomized, placebo-controlled trial (, identifier NCT01208090) involving 326 patients who were randomized to receive ponesimod 20 mg, 40 mg or placebo for a 16-week induction period, followed by rerandomization to a 12-week maintenance period.[26] At 16 weeks, 46% of the 20 mg group and 48.1% of the 40 mg group reached the primary endpoint of PASI 75 compared to 13% of patients receiving placebo. At week 28, the end of the maintenance period, the PASI 75 score further improved to 71% and 77% for the 20 mg and 40 mg groups, respectively, compared to 42% and 40% of patients who were re-randomized from ponesimod to placebo.[26] Safety analysis revealed an expected decrease in lymphocyte counts, which returned to baseline values 2 weeks after discontinuation of therapy and was not associated with an increased risk of infection. Other notable effects include dyspnea, transaminitis, nasopharyngitis, headache and dizziness.[26]