Targeting the Pathways: TNF, IL-17, and IL-23 in Psoriasis

This episode, "Targeting the Pathways: TNF, IL-17, and IL-23 in Psoriasis," features the panel unpacking the biology behind today's biologics.

Dr. Wright emphasizes how complex psoriatic disease is, despite looking like just skin and joints. She runs through the targetable pathways: TNF inhibitors, IL-17 inhibitors across the class, whether IL-17A or IL-17AF, and IL-23 inhibitors. She adds agents that work below those pathways, including JAK and TYK2 inhibitors.

Dr. Wright rejects a linear view of the immune response. She describes it as a globe or sphere, where disrupting one node feeds forward and backward through a circuit. Blocking IL-17, for example, can produce feedback that dampens the IL-23 pathway, while TNF-alpha keeps its own distinct receptor and role. Her point is that clinicians must think about the specific molecules and cells in the disease they are treating. She notes that rheumatology once borrowed everything from rheumatoid arthritis, down to its outcome measures, and must now reason from the biology instead.

Dr. Han agrees the discussion was strong but offers a counterpoint for the skin. He argues psoriasis is fortunate to run through a fairly linear central pathway for most patients, flowing through IL-23, TX-17, and IL-17. He acknowledges non-IL-23 sources of IL-17 and other immune circuits exist, but maintains that blocking the central pathway resolves most psoriasis.

Dr. Han frames each successive drug class as more targeted with fewer side effects. He tells patients these therapies are not broadly immunosuppressive, since they narrowly block one overactivated branch while leaving the rest of the immune system intact. That knowledge, he says, puts psoriasis treatment far ahead of where it stood 10 or 20 years ago.

In "IL-17 vs IL-23: Head-to-Head Data in Psoriasis and PsA," Dr. Wright and Dr. Han compare how IL-17 and IL-23 inhibitors perform in the skin and joints, drawing on the head-to-head data that anchors this series.