Oral Icotrokinra Reaches 54% PASI 100, a First for a Psoriasis Pill

An oral psoriasis therapy has achieved 54% PASI 100 (complete clearance on the Psoriasis Area and Severity Index) roughly a month into treatment — a result Mark Lebwohl, MD, calls unprecedented for a pill. "For an oral therapy to achieve 54% PASI 100, even a month after treatment, is quite an accomplishment and something we have not seen before with a pill," said Lebwohl, dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai and chairman emeritus of the Mount Sinai dermatology department.

Lebwohl discussed icotrokinra (Icotyde; Johnson & Johnson), envudeucitinib (Alumis), and zasocitinib (Takeda) in a recent Dermatology Times Expert Perspectives custom video series. His remarks covered response over time, difficult anatomic sites, durability, and monitoring requirements across drug classes.

How quickly do these oral agents work?

Icotrokinra and the TYK2 inhibitors (agents blocking tyrosine kinase 2, an intracellular signaling enzyme in the IL-23 pathway) do not peak at 16 weeks, Lebwohl said. Patients continue gaining benefit through 24 weeks, so the maximum effect arrives later than clinicians may expect from trial endpoints.

"While they may be a little bit slower getting to their peak effect, their peak effect is pretty good," Lebwohl said.

One caveat shadows that figure. The durability and longer-term response data come from an open-label extension without a placebo control, a design that tends to inflate apparent efficacy. Lebwohl also noted that many biologics and oral therapies reach higher PASI 100 rates as patients approach a full year of treatment, which sets the bar these agents must clear.

What about scalp, nail, and palm and sole disease?

Scalp involvement is common, and itching in those patients is particularly severe. Lebwohl said the oral agents treat the scalp across the board, and most patients respond to the same drugs used elsewhere on the body.

Response separates in two locations. Fingernails lag behind the rest of the body because the nail bed and nail matrix must normalize before the nail grows out, a process that usually takes months.

Palm and sole disease is the second exception. Lebwohl suggested that large biologic molecules may struggle to reach the thick stratum corneum through small peripheral vessels, which could explain their limited efficacy in hands and feet. Oral agents are far smaller molecules, and good palm and sole responses have been reported largely with oral JAK inhibitors (Janus kinase inhibitors, a class blocking intracellular signaling).

How durable is the response?

Durability appears quite good so far, Lebwohl said, though he acknowledged attrition, including loss of efficacy and dropouts from inadequate response. "The patients who stay on the drug, a very high proportion of them will remain responsive to the drug for long periods of follow-up," he said.

That formulation deserves scrutiny. Durability measured in patients who remain on therapy excludes those who quit, and open-label follow-up cannot rule out selection effects.

What monitoring does each class require?

Monitoring depends on the drug, Lebwohl said:

• JAK inhibitors, used primarily for psoriatic arthritis, require a CBC (complete blood count), chemistry screens, lipid panels, and an annual TB (tuberculosis) test.
• IL-17 and IL-23 blockers have not been shown to reactivate latent TB, and the FDA has been asked to remove the testing requirement for them.
• TNF blockers, JAK inhibitors, methotrexate, and cyclosporine do reactivate latent TB, so testing remains necessary.

"Yeast infections are a known side effect of IL-17 inhibitors, but they tend to be very mild," Lebwohl said. Such infections usually involve the tongue, a condition called thrush, and are easily treated.

Lebwohl framed the broader shift plainly: the field has finally entered an era of drugs with almost no immunosuppression. Whether the 54% PASI 100 figure and the durability claims hold up in placebo-controlled, long-term data will determine how quickly these oral agents reshape psoriasis practice.