Emerging Novel Treatments for Plaque Psoriasis

On the second day of Dermatology Week, Elizabeth Wallace, MD, FAAD, presented during her session titled, “Advances in the Management of Plaque Psoriasis: Emerging Novel Treatments.”

To start, Dr Wallace reviewed the current treatment options available to patients with psoriasis including:

• Topical psoriasis treatment (corticosteroids, vitamin D analogs, vitamin A derivatives)
• Traditional oral psoriasis treatment (methotrexate, cyclosporine, acitretin)
• Small molecule inhibitor (apremilast)

Dr Wallace noted that “these medications can affect intracellular signal transduction pathways, they all have the advantage of being orally administered, but traditional oral psoriasis medications require close [laboratory] monitoring for toxicity and frequent patient check-ins to assess for adverse events.”

Additionally, she reviewed the available biologic medications such as TNF inhibitors, IL-17 inhibitors, IL-12/23 inhibitor, and IL-23 inhibitors.

In continuation, she referenced the National Psoriasis Foundation's recent surveys that recorded members with psoriasis or psoriatic arthritis on disease burden, treatment, and quality of life in addition to highlighting the challenges patients face with current options. These challenges consisted of mode of delivery, potential side effects, poor efficacy, affordability, and accessibility.

“So, what are some strategies to address these challenges that patients face?” asked Dr Wallace.

She continued by listing what steps physicians might take such as:

•  
• Confirming the diagnosis of psoriasis and telling the patient about their disease by educating them about the associated comorbidities
• Helping them navigate and see who their comprehensive care team should be
• Setting expectations (chronic skin disease that requires long-term treatment)
• Collaborating on an individualized treatment plan
• Taking into account other medical conditions
• Layout a clear follow-up plan
• Setting expectations when they can expect to see the medication start working
• Consider sharing a plan B (the next step for when current treatment plan does not meet patients’ treatment goals)

Dr Wallace continued her presentation by introducing four emerging therapies that offer treatment advances in psoriasis, starting with an emerging aryl hydrocarbon receptor (AhR) modulator tapinarof. It has been found to decreases TH17 cytokines, which results in decreased inflammation; increased filaggrin, loricrin, and involucrin to improve the skin barrier; and increased antioxidant response via NRF2 pathway for a decrease in oxidative stress.

Next was emerging phosphodiesterase (PDE) 4 inhibitor roflumilast. Dr Wallace explained that phosphodiesterase are one of the primary enzymes that determine intracellular concentrations of cyclic adenosine monophosphate (cAMP) in immune cells endothelial cells and keratinocytes. When PDE4 is inhibited, intracellular levels of cAMP rise, and since cAMP regulates inflammatory responses, increased levels can lead to downregulation of inflammatory cytokines. Roflumilast is a topical PDE4 inhibitor that showed high efficacy and low adverse events in recent studies.

Dr Wallace also presented the emerging tyrosine kinase 2 (TYK2) inhibitor deucravacitinib. Deucravacitinib is an oral TYK2 inhibitor currently under investigation for the treatment of psoriasis. In a recent phase 3 study, deucravacitinib was compared with placebo and apremilast; the study showed greater efficacy by week 16, with increased improvement for patients continuing the medication. In the case of adverse effects (AEs), deucravacitinib showed a heightened risk of AEs but lower than apremilast based on the study's safety results.

Finally, Dr Wallace ended her presentation by introducing the emerging IL-17A and IL-17F inhibitor bimekizumab. Bimekizumab is a monoclonal antibody that selectively inhibits both IL-17A and IL-17F. Recent literature found bimekizumab to have strong efficacy but with higher treatment-emergent AEs compared with a placebo; additionally, another study found that bimekizumab had higher efficacy than ustekinumab but, again, higher AEs were reported as well.

Reference
Wallace, E. Advances in the management of plaque psoriasis: emerging novel treatments. Presented at: Dermatology Week 2021; September 16-19, 2021; virtual.