Phase 2 Study of Tofacitinib for Psoriasis Shows Specific Immune System Changes

Phase 2 Study of Tofacitinib for Psoriasis Shows Specific Immune System Changes

A new study of the medication tofacitinib sheds light on how it may work to treat psoriasis. The research report, Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: A randomized phase 2 study, was published in the Journal of Clinical Allergy and Clinical Immunology.

Tofacitinib is a medication that blocks the janus kinase (JAK) inhibitor. It was discovered and developed by both the National Institutes of Health (NIH) and the pharmaceutical company Pfizer, and marketed under the brand names Xeljanz and Jakvinus. It was approved in the United States and other countries for the treatment of rheumatoid arthritis. Because it blocks inflammation, it may be effective for psoriasis, as well.

Psoriasis is an inflammatory disease, which means that the immune system is overactive. It causes skin rash, but can also affect the nails or joints, inducing excessive cells to build up. Plaque psoriasis is a common form, in which red patches of skin appear. Blocking inflammation via JAK inhibition could be a possible treatment for psoriasis.

The researchers, led by James Krueger of Rockefeller University in New York City, wanted to understand  the biological mechanisms that make tofacitinib effective in patients with psoriasis. They studied 12 patients with plaque psoriasis who were given 10 mg of tofacitinib or a placebo twice a day for 12 weeks. The investigators took skin samples to identify cell changes caused by the medication and to measure skin improvement.

They found that tofacitinib improved the skin condition by inhibiting JAK, as expected. In addition, at weeks 1 and 2, tofacitinib reduced immune molecules known as cytokines that are made by cells in the skin called keratinocytes. It also reduced immune cells, specifically dendritic cells and T-cells. By the fourth week, tofacitinib reduced a cytokine pathway known as IL-23/TH17, and the reduction continued to week 12, the final week of the study.

Skin improvements were specifically related to certain cytokines and cell changes. The researchers noted this in their study report, stating, “Improvements in clinical and histologic features were strongly associated with changes in expression of psoriasis-related genes and reduction in IL-17 gene expression.”

Overall, tofacitinib seems to improve psoriasis in several different ways and by modulating several different aspects of inflammation. Understanding these specific cellular changes supports the use of tofacitinib for psoriasis as an inhibitor of inflammation, and also suggests possible targets for new psoriasis treatments.

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