Brodalumab efficacious in palmoplantar pustulosis treatment

MILAN — Brodalumab proved to be an effective treatment for Japanese patients with palmoplantar pustulosis in a 16-week phase 3 trial.

“In this phase 3, placebo-controlled, double-blind study we assess the efficacy and safety of brodalumab in Japanese patients with [palmoplantar pustulosis (PPP)] and moderate or severe pustules and vesicles,” Yukari Okubo, PhD, of the department of dermatology at Tokyo Medical University, said during the presentation at the European Academy of Dermatology and Venereology Congress.

Patients with PPP have an increased amount of T-helper 17 cells and interleukin-17A (IL-17A) concentration in the blood, as well as an accumulation of T-helper 17 cells and IL-17 mRNA expression in the affected cutaneous tissues. However, brodalumab, a fully human immunoglobulin G2 monoclonal antibody, can selectively bind to IL-17 receptor A and inhibit the malignant signaling.

Eligible study participants were aged 17 to 80 years with a PPP diagnosis of at least 24 weeks, a PPP Area Severity Index (PPPASI) score of 12 or greater, and a PPPASI sub score of pustules/vesicles of 2 or greater. These patients were also nonresponsive to topical treatments leading up to the trial.

Patients were randomly assigned 1:1 to receive brodalumab 210 mg at weeks 0, 1 and 2, and then every 2 weeks thereafter, or placebo. At week 16, all subjects entered an open label extension phase and received 210 mg of brodalumab every 2 weeks.

The primary endpoint, to see a trend of improvement from baseline in PPPASI total score by week 16, was much higher in the brodalumab group compared with the placebo group (mean change, 13.73 vs. 8.45).

Additionally, the brodalumab group more rapidly achieved a 50% or 75% greater improvement in PPPASI response throughout the trial. Also, 16% of the brodalumab group achieved a 90% or greater improvement in PPPASI response by week 16 compared with 0% in the placebo group.

The total PPP Severity Index and Physician Global Assessment scores showed greater improvement in the brodalumab group. However, the change from baseline in Dermatology Life Quality Index was comparable between groups at week 16 (brodalumab, 2.3 vs. placebo, 2.7).

Commonly reported treatment-emergent adverse events in the brodalumab vs. placebo group were otitis externa (25.4% vs. 1.6%), folliculitis (15.9% vs. 3.2%), nasopharyngitis (14.3% vs. 4.8%) and eczema (14.3% vs. 12.9%), with grade 1 or 2 severity. There was no suicidal ideation or behavior reported.

“Brodalumab for 16 weeks was effective and tolerable in Japanese patients with PPP,” Okubo said. “Brodalumab may provide a new treatment option for patients with palmoplantar pustulosis.”