In this video blog, Dr. Jason Hawkes summarizes his lecture in the panel discussion, Psoriasis Evolution: Where We've Been and What's To Come , given on November 9, 2024, 5th Annual Elevate-Derm West Conference at the Westin Kierland Resort in Scottsdale, AZ.

In this video

Dr. Hawkes describes how the oral psoriasis space stalled for nearly a decade after apremilast, which filled an important gap for patients who wanted a pill safer than methotrexate, cyclosporine, or acitretin but was "not all that effective in the skin" and carried high rates of GI side effects. The first-in-class TYK2 inhibitor deucravacitinib roughly doubled that efficacy by targeting the IL-12/23 pathway and some type I interferons, delivering PASI 100 responses with once-daily dosing and far fewer GI issues. He notes it is a slower agent, with optimal response around 24 weeks, and that its main knock is efficacy still below the biologics — the persistent gap that has "been troubling the oral psoriasis treatment space."

He is most excited about an oral IL-23 receptor blocker in development, which in phase 2 has about four in ten patients reaching PASI 100 — the first oral pill he says has "crashed into" biologic-like efficacy and truly closes the oral-versus-biologic gap. Turning to less common subtypes, Dr. Hawkes stresses that "we talk about psoriasis as if it's all the same" when we're mostly describing plaque disease. He points to spesolimab's IL-36 receptor blockade for generalized pustular psoriasis as a model for real personalized medicine and hopes the next five years bring subtype-specific studies for recalcitrant variants like palmoplantar pustulosis, so treatment moves from trial-and-error probabilities toward matching a phenotype to a therapy.

  • Apremilast filled a real gap for patients wanting an oral option safer than methotrexate, cyclosporine, or acitretin, but its skin efficacy was modest and GI side effects often drove discontinuation.
  • Deucravacitinib, a first-in-class TYK2 inhibitor, roughly doubled oral efficacy (reaching PASI 100), is once-daily and generally well tolerated; watch for herpes reactivation from type I interferon blockade, some headache, and about a 10% shift in lipids (mainly triglycerides), and set expectations for optimal response around 24 weeks.
  • An investigational oral IL-23 receptor blocker showed roughly four in ten patients hitting PASI 100 in phase 2 — the first oral agent approaching biologic-like efficacy and giving patients who prefer pills a genuinely comparable choice.
  • Most psoriasis data reflect plaque disease (about 85% of patients); inverse and non-pustular palmoplantar disease usually respond to IL-23/17 blockade, but palmoplantar pustulosis remains harder to treat.
  • Spesolimab's IL-36 receptor blockade for GPP (IV for acute flares, subcutaneous for maintenance) is a model of phenotype-driven, personalized therapy Dr. Hawkes hopes to see extended to other recalcitrant subtypes over the next five years.