Emerging Treatments | Dermatology

Session Focus

The panel covered why psoriasis became dermatology’s model for targeted drug development, what that success has and has not taught the field about other inflammatory skin diseases, how new oral options are changing prescribing, and the role of devices alongside drugs.

Devices as More Than Lasers

Avery LaChance MD opened the device discussion by widening the definition considerably. Devices intersect with the drug space in several directions: improving how deeply topicals penetrate, UV and home phototherapy units for inflammatory skin disease, and the delivery mechanisms for biologics themselves.

Her point about the last category is easy to overlook. How a biologic is injected creates a substantial difference in medication uptake and adherence, and the goal is delivery that is effective and painless.

How Psoriasis Became the Model

LaChance described the path as having arrived through a back door. Anti-TNF agents produced remarkable responses for both skin and joints at the time, but were a broad sledgehammer, game-changing relative to topicals, phototherapy and coal tar techniques.

Curiosity about why they worked drove translational research into which pathway actually drives psoriasis, revealing how anti-TNF intersected with more targeted molecular pathways, IL-17 and IL-23.

The pattern that followed: as therapies became more targeted, efficacy improved and side effects decreased. The questions then shifted to reducing injection frequency while maintaining efficacy, and eventually to orals effective enough to let clinicians meet patient preference.

John Harris MD, PhD added the timeline and the economics. It took roughly thirty years. In his training, methotrexate was the primary option before TNF.

His explanation of why TNF mattered scientifically: blocking it made the disease go away, which established immunologically that it is mechanistically involved and gave the field a point of reference. Basic science then established IL-17 as upstream and IL-23 upstream of that.

Psoriasis was at one point a $14 billion annual industry and is now $20 to $30 billion with fourteen drugs targeting different parts of that pathway, each exceeding a billion dollars.

On IL-23 inhibitors he recounted Jim Krueger’s observation from ten or fifteen years ago that patients given an IL-23 inhibitor and nothing else remained clear for a year. The field now understands why: the target sits far enough upstream to eliminate the memory cells driving psoriasis, so stopping the drug does not bring the disease back because the memory has been erased.

Harris also described the field’s downside candidly. Early in his career, companies cared about nothing else. He would bring a new target and be told to try it in psoriasis first. His response was that it had nothing to do with psoriasis but was a big market that particular molecule could not address. That block persisted until IL-23 inhibitors became so effective that companies concluded they could not do much better and had to consider atopic dermatitis, vitiligo, alopecia areata, hidradenitis suppurativa and chronic urticaria.

His wry addendum: succeed in making drugs with long remission times and they will hate you again.

Why an Oral Is Gaining Ground

Asked about a newer oral entrant against the disappointing launch of a predecessor, LaChance identified three factors.

Biologic-like efficacy. For the first time an oral encroaches on biologics. She explained why the earlier launch struggled: in a landscape where injectable therapeutics clear patients with very few injections, leading with PASI 75 data prompts the question of whether the drug is good enough, since PASI 90 and PASI 100 are what the field looks for.

A clean safety profile. Adverse events are almost a blank slate, against a comparator oral whose GI upset patients tolerated poorly.

No lab monitoring requirement. The earlier oral generated confusion about whether JAK-like black box concerns and monitoring applied, including tuberculosis testing, which this agent does not require.

Together she described these as producing a frictionless prescribing experience, and something more important clinically: the first genuine ability to ask a patient at the bedside whether they prefer oral or injectable.

She was careful not to assume the answer. When Otezla launched, everyone expected patients to want an oral, and in practice many patients prefer injecting themselves four times a year.

On market dynamics, her early experience is that the oral is creeping into biologic territory, particularly for patients with injection fatigue, while clearly taking share from other orals.

Atopic Dermatitis and the JAK Hesitation

LaChance described current practice as still starting most patients on biologics, with dupilumab and lebrikizumab the two main competitors.

Despite lebrikizumab offering similar efficacy with injections spaced to every four weeks rather than every two, dupilumab retains substantial market share on the strength of historical use and clinician comfort.

The notable gap is that both sit below the JAK inhibitors on efficacy, with upadacitinib regarded as the gold standard and abrocitinib also higher than the biologics.

Her explanation for why the more effective agents are not used first: the JAKs launched in rheumatoid arthritis, which is where they acquired their black box warning. That produces continued hesitation among patients and among community dermatologists, so the JAKs are reserved for more treatment-refractory or severe patients.

Harris interjected with a reminder about what precedes any of these decisions. Atopic dermatitis is a barrier problem, and the classic unglamorous measures, moisturizing and basic skin care, come first.

Key Takeaways

1. Psoriasis took roughly thirty years to reach targeted therapy, moving from methotrexate through TNF to IL-17 and IL-23.

2. Targeting further upstream improved efficacy and reduced side effects simultaneously.

3. IL-23 inhibition erases the memory cells driving psoriasis, which is why remission persists after stopping treatment.

4. Commercial success in psoriasis actively blocked development in other skin diseases until the field saturated.

5. A new oral matches biologic efficacy with a clean safety label and no lab monitoring, enabling genuine patient choice.

6. Patient preference does not default to orals. Many choose four injections a year.

7. In atopic dermatitis the most effective agents are used last, because JAK black box warnings originated in rheumatoid arthritis.