TYK2 inhibitor looks good for lichen planopilaris

Deucravacitinib, an oral selective inhibitor of tyrosine kinase 2 (TYK2), shows promise in the treatment of lichen planopilaris (LPP), with substantial reductions in disease activity, according to the interim analysis of an open-label, single-arm trial.

The Lichen Planopilaris Activity Index (LPPAI) score decreased from 3.8 at baseline to 1.6 at week 12 and 1.2 at week 16, corresponding to about a 60-percent and 70-percent improvement, respectively, reported principal investigator Dr Aaron Mangold from the Mayo Clinic Dermatology in Scottsdale, Arizona, US. [EADV 2024, abstract 7862]

In addition, Physician Global Assessment (PGA) 0–3 response* significantly increased, with the proportion of patients achieving a greater than 50-percent improvement rising from 20 percent at week 2 to 80 percent at week 12 (p=0.024) and 100 percent at week 16 (p=0.005).

Looking at parallel responses in LPPAI and Itch Numerical Rating Scale (NRS), Mangold noted a distinct pattern in LPP. Unlike atopic dermatitis, where itch relief often precedes clinical improvement, LPP patients experienced a more rapid improvement in their clinical symptoms before noticing a significant reduction in itch.

“The average time to greater than 50-percent improvement in LPPAI was about 5.8 weeks, whereas the average time to greater than 50-percent reduction in Itch NRS was 11.1 weeks,” he said.

Mangold presented a series of side-by-side patient photos, comparing baseline and week 24 conditions. He pointed to significant reductions in perifollicular inflammation, scaling, and erythema following treatment with deucravacitinib. Notably, in one patient, response was maintained even after discontinuing therapy.

Safety

“Deucravacitinib was well tolerated,” Mangold said. “We didn’t see any serious treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation.”

A total of 13 mild drug-related AEs occurred, with the most common being acne (70 percent). Other less common AEs were hand dermatitis, rash around neck/ears/face, and cold or flu. Of these AEs, 83.3 percent improved or resolved upon cessation of therapy.

The interim analysis included 10 heavily pretreated adult patients (mean age 61.4 years, 70 percent female, 100 percent White) with biopsy-proven active LPP (median disease duration 6.4 years). The mean number of prior treatments was 4.1, while the mean number of systemic therapies was 1.7. Six patients had received intralesional injections, and one patient had skin-directed therapy.

Deucravacitinib was given at 6 mg two times a day for 24 weeks. A washout period of 2 weeks for topical and 4 weeks or longer for systemic agents was required. Efficacy and safety evaluations were conducted every 4 weeks through week 24. An additional follow-up of 4 weeks post-treatment was conducted.

“Additional controlled studies are needed to assess the safety and efficacy of deucravacitinib in LPP,” according to Mangold, who shared news of pending molecular data from bulk spatial and single-cell sequencing.