Evolution and Innovation in Treating Psoriasis in Pediatric Patients

“When we talk about evolution in treatment for psoriasis, we have come a long way,” April W. Armstrong, MD, MPH, told attendees at the Society for Pediatric Dermatology Pre-AAD Meeting.¹

April W. Armstrong, MD, MPH

Armstrong, Chief of the Division of Dermatology at the UCLA Health and the David Geffen School of Medicine, added that through this evolution we are looking for treatments that are effective, convenient and safe. Not too long ago, arsenic was used to treat psoriasis,² she told attendees. “Yes, it killed psoriasis but also killed a lot of other things.”

Fortunately, she shared there are now options that are meet the 3 important criteria: safe, effective, and even convenient. For instance, biologics have emerged as a good option for treating psoriasis, especially in adults, Armstrong explained. In general, there are a number of factors she considers when choosing among the biologics, which when grouped include tumor necrosis factor (TNF) inhibitors (ie, etanercept, infliximab, adalimumab, certolizumab), interleukin (IL)-17 inhibitors (ie, ixekizumab, secukinumab, brodalumab, bimekizumab), and IL-23 inhibitors (ie, guselkumab, risankizumab, tildrakizumab, ustekinumab [a IL12/23 inhibitor]).

The IL-17 and IL-23 inhibitors are a good choice for robust psoriasis efficacy. In addition, guselkumab, risankizumab, ustekinumab have been shown to be effective for psoriatic arthritis, while IL-17 inhibitors have been shown to be effective for peripheral and axial psoriatic arthritis. There is evolving evidence for the use of IL-23 inhibitors in psoriatic arthritis of the spine. She cautioned that IL-17 inhibitors should be avoided in patients with a history of inflammatory bowel disease and can be associated with increased risk of oral candidiasis.

Meanwhile, Armstrong noted TNF inhibitors should be avoided in patients with hepatitis B and demyelinating disease. They also are not preferred when there is a history of latent tuberculosis or advanced congestive heart failure. Like the other biologics, TNF inhibitors can be effective for psoriatic arthritis (peripheral and axial) and she added that certolizumab has been great in pregnant patients.

Currently, there arebiologics approved for use in pediatric patients. Ustekinumab which inhibits p40 subunit of IL12/23, has been approved for pediatric plaque psoriasis in patients aged 6 years and older. She pointed to the CADMUS Trial, which found that nearly 70% of patients aged 12 years or older with moderate to severe plaque psoriasis achieved sPGA0/1 (vs 5.4 in the placebo group).³

Secukinumab is approved for pediatric patients aged 6 years and older, she said. She shared results from a study comparing secukinumab versus etanercept in this patient population, noting she especially appreciates head to head comparisons of agents because it speaks to the superiority of one medication over another over a time period. In the study, which was present at the EADV Virtual Congress in 2020, 85% of the patients on secukinumab achieved (and maintained) clear (IGA 0/1) at 52 weeks vs 72% on etanercept.

Approved in pediatric patients 6 years and older for moderate to severe psoriasis, Armstrong said ixekizumab has shown high efficacy when compared with placebo, with 50% of patients achieving PASI 100 by week 12 (vs 2% on placebo).

Bimekizumab, the newest approved biologic for adult patients, has shown fast onset, high efficacy, and robust maintenance of response, Armstrong told attendees. Treatment consists of two 160 mg doses every 4 weeks for the first 16 weeks and then every 8 weeks afterwards. She reminded attendees that labs (ie, tuberculosis, liver enzymes, alkaline phosphatase, and bilirubin) should be checked prior to treatment. Oral candidiasis is the most common adverse event, but she said it is manageable without discontinuation with 100 mg to 200 mg fluconazole for 7 days.

Meanwhile, a phase 2 trial of bimekizumab (NCT04718896) is currently underway to assess safety and efficacy in adolescents with moderate to severe plaque psoriasis.

Another important treatment to consider is the tyrosine kinase 2 (Tyk2) inhibitor deucravacitinib, Armstrong told attendees. Currently, deucravacitinib is approved by the US Food and Drug Administration as an oral medication for the treatment of moderate to severe plaque psoriasis in adults. She shared data demonstrating Psoriasis Area and Severity Index (PASI) 75, PASI 90, and Static Physician's Global Assessment (sPGA) 0/1 response sustained through 3 years for patients on the agent, which she added “is really impressive”.

“The tolerability is really where it shines,” Armstrong told attendees. It has rates of diarrhea and nausea similar to placebo, and there are low rates of acne and zoster, she explained, but overall the discontinuation rates was lowest for patients on deucravacitinib when compared with patients on placebo or apremilast.

Before initiating treatment, Armstrong noted patients should be evaluated for tuberculosis and baseline liver and hepatitis serologies should be checked in patients with known or suspected liver disease. However, ongoing monitoring is only needed if the patient has liver disease or unmanaged triglycerides.

“I’m very excited about the possible extension to our pediatric population in the future,” Armstrong said. She detailed a phase 3 trial (NCT04772079) is currently underway for pediatric patients with moderate to severe plaque psoriasis looking at safety and efficacy in that patient population. The study is looking at 2 doses across 2 cohorts based on ages (4 to 12 and 12 to 18 years).

The oral phosphodiesterase 4 (PDE4) inhibitor apremilast is also a new medication that has shown efficacy in pediatric patients, according to Armstrong. It currenly is approved for adults regardless of severity, she said. She shared results of a placebo-controlled study of patients with moderate to severe plaque psoriasis aged 6 to 17 years that found almost one-third were clear or almost clear at week 16 (vs 11% for placebo).

Armstrong briefly noted 2 innovative products in the pipeline. JNJ-77242113 is an oral therapeutic peptide selectively targeting IL-23R, she told attendees.⁴ DC-806 allosterically blocks the same biochemical step as the anti-IL-17 antibodies.

In the topical category, Armstrong pointed to tapinarof and roflumilast as novel non-steroidal agents. Tapinarof, currently approved for adult patients, is an aryl hydrocarbon receptor (AhR) agonist that reduces TH17 cytokines; increases antioxidant activity via Nrf2 pathway; increases filaggrin, loricrin, and involucrin, and decreases Th2 cytokines. The PSOARING 1 study found that 40% of patients on tapinarof 1% cream daily achieved PASI 75 by week 12. Armstrong added that when tapinarof is stopped, patients are able to maintain clear/almost clear status for about 4 months. “My opinion is it is probably similar to or stronger than a class 3 topical steroid,” she told attendees. Armstrong is hopeful it will become available for pediatric patients in the near future.

Roflumilast is a PDE4 inhibitor approved for patients aged 6 years and older, Armstrong said. Overall it is quite well tolerated. “In my opinion, it is probably similar to a class 3 topical steroid,” she said. She uses it in clinical practice, but there are some tricks to make sure your patient has access to it, and knowing which local pharmacies are used to working with it.

References

1. Armstrong A. Updates in Psoriasis Management and New Therapeutics. Presented at: 36th Annual Pre-AAD Meeting of the Society for Pediatric Dermatology; March 7, 2024. San Diego, California.

2. Sarfraz R. H16 Arsenic to biologics: psoriasis treatment through the ages. British Journal of Dermatology. 2023; 188(Supplement 4. ljad113.298

3. Landells I, Marano C, Hsu MC, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study. J Am Acad Dermatol. 2015;73(4):594-603. doi:10.1016/j.jaad.2015.07.002

4. Bissonnette R, Pinter A, Ferris LK, et al. An Oral Interleukin-23-Receptor Antagonist Peptide for Plaque Psoriasis. N Engl J Med. 2024;390(6):510-521. doi:10.1056/NEJMoa2308713