Guselkumab for the Treatment of Palmoplantar Pustulosis: A Japanese Perspective

Abstract

Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder characterized by sterile pustules predominantly involving the palms and soles. PPP is refractory to various therapies such as topical ointment, oral medicine, and phototherapies. Pustulotic arthro-osteitis (PAO) is a major comorbidity of PPP that severely impairs patients’ quality of life. Recently, guselkumab, a monoclonal antibody against IL-23, has been available for the treatment of PPP in Japan. The purpose of the present review is to describe the characteristics of Japanese PPP patients and biologic therapy of PPP/PAO using guselkumab. Most Japanese dermatologists consider PPP as a distinct entity and co-existence of PPP and psoriasis is rare. However, outside Japan, PPP is often considered to be palmoplantar psoriasis, and extra-palmoplantar lesions associated with PPP are regarded as psoriasis. PPP develops or exacerbates either with or without arthralgia, following focal infections, such as tonsillitis, odontogenic infection, and sinusitis. Treatment of focal infection results in dramatic effects on cutaneous lesions as well as joint pain. By contrast, we sometimes see patients whose skin/joint symptoms do not improve after treatment of focal infection, whose focus of infection cannot be identified even in a detailed examination, and/or who refuse tonsillectomy even if strongly recommended. Such cases are considered to be indications of biologics. In this review, clinical features, pathophysiology and guselkumab therapy are discussed.

A view on the skin–bone axis: unraveling similarities and potential of crosstalk

“…With regard to inflammatory cytokines, psoriasis is associated with elevated levels of TNFα, IL-23, and IL-17, with these cytokines also having a significant impact on bone erosion in psoriatic arthritis ( 60–62 ). In addition, highly effective antibody therapies (biologics) targeting these cytokines have been developed, with a growing list of new inhibitory antibodies being investigated ( 60 , 61 ). Inflammatory cytokines such as TNF-α, IL-6, and IL-17 are also implicated in chronic urticaria ( 53 ), atopic dermatitis ( 63 ), and bullous diseases ( 64 , 65 ).…”

Spesolimab Efficacy and Safety in Patients with Moderate-to-Severe Palmoplantar Pustulosis: A Multicentre, Double-Blind, Randomised, Placebo-Controlled, Phase IIb, Dose-Finding Study

“…Similarly, smaller studies have reported modest or no clinical benefits with etanercept [ 11 ] and ustekinumab [ 12 , 13 ], and a phase II exploratory study and case studies have shown clinical benefit with apremilast [ 14 , 15 ]. Guselkumab, a monoclonal anti-interleukin (IL)-23 antibody, has shown efficacy in clinical trials and is approved for PPP treatment in Japan [ 16 – 18 ]. However, the difference between guselkumab and placebo with respect to the least-squares mean change from baseline in Palmoplantar Pustular Area and Severity Index (PPP ASI) score at week 16 of a phase III trial was only − 7.7 (guselkumab 100 mg) and − 4.1 (guselkumab 200 mg), suggesting relatively modest efficacy [ 18 ].…”

Drug survival of biologics and non‐biologics in patients affected by palmoplantar psoriasis: a “real‐world”, mono‐center experience

“…According to a systematic review, 8 biologics can be effective in both hyperkeratotic PP and pustular PP 9 . Noteworthy, guselkumab, an anti‐IL‐23A monoclonal antibody, was recently approved in Japan for the treatment of pustular PP in patients refractory to previous conventional treatments, after an RCT showed its safety and efficacy at 16 weeks, that was maintained up to 52 weeks 10 …”