Optimal treatments and outcome measures of palmoplantar pustulosis: A systematic review and network meta‐analysis‐based comparison of treatment efficacy

Fukasawa, Takemichi; Yamashita, Takashi; Enomoto, Atsushi; Yoshizaki‐Ogawa, Asako; Miyagawa, Kiyoshi; Sato, Shinichi; Yoshizaki, Ayumi

doi:10.1111/jdv.19499

Cited by 5 publications

(2 citation statements)

References 52 publications

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“…This process is crucial for the activation of CD4+ T cells when sensitized to minimal antigenic stimuli, a mechanism believed to be pivotal in the development of autoimmune diseases. [4][5][6][7][8][9][10] The significance of CD4+ T cells in the pathogenesis of SSc has been particularly underscored. 11 Furthermore, B cells play a role in the regulation of lymphoid tissue construction and regeneration, as evidenced by the substantial reduction in thymocytes, splenic dendritic cells, and T cells in mice lacking B cells.…”

Section: Introduction: the Fun C Ti On Of B Cell S In The Pathog Ene ...mentioning

confidence: 99%

The role of B cells in systemic sclerosis

Fukasawa,

Yoshizaki‐Ogawa,

Sato

et al. 2024

The Journal of Dermatology

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Systemic sclerosis (SSc) is a rare and refractory systemic disease characterized by fibrosis and vasculopathy in the presence of autoimmune abnormalities. While the exact cause of SSc is incompletely understood, the specific autoantibodies identified in SSc are closely linked to disease severity and prognosis, indicating a significant role of autoimmune abnormalities in the pathogenesis of SSc. Although the direct pathogenic mechanisms of autoantibodies in SSc are not fully elucidated, numerous prior investigations have demonstrated the involvement of B cells in the pathogenesis of SSc through various mechanisms. Additionally, several clinical trials have explored the efficacy of B‐cell depletion therapy for SSc, with many reporting positive outcomes. However, the role of B cells in SSc pathogenesis is multifaceted, as they can both promote inflammation and exert inhibitory functions. This article provides an overview of the involvement of B cells in SSc development, incorporating the latest research findings.

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Section: Introduction: the Fun C Ti On Of B Cell S In The Pathog Ene ...mentioning

confidence: 99%

The role of B cells in systemic sclerosis

Fukasawa,

Yoshizaki‐Ogawa,

Sato

et al. 2024

The Journal of Dermatology

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“…[IL]-17 and IL-23 blockers) or generalized pustular psoriasis (IL-1 and IL-36 blockers). These therapeutics, however, showed limited efficacy in PPP is limited [4][5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

A genome-wide meta-analysis of palmoplantar pustulosis implicates Th2 responses and cigarette smoking in disease pathogenesis

Hernandez-Cordero,

Thomas,

Smail

et al. 2024

Preprint

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BackgroundPalmoplantar pustulosis (PPP) is an inflammatory skin disorder that mostly affects smokers and manifests with painful pustular eruptions on the palms and soles. While the disease can present with concurrent plaque psoriasis, TNF and IL-17/IL-23 inhibitors show limited efficacy. There is therefore a pressing need to uncover PPP disease drivers and therapeutic targets.ObjectivesTo identify genetic determinants of PPP and investigate whether cigarette smoking contributes to disease pathogenesis.MethodsWe performed a genome-wide association meta-analysis of three North-European cohorts (n=1,456 PPP cases and 402,050 controls). We then used the scGWAS program to investigate the cell-type specificity of the resulting association signals. We undertook genetic correlation analyses to examine the similarities between PPP and other immune-mediated diseases. Finally, we applied Mendelian randomization to analyze the causal relationship between cigarette smoking and PPP.ResultsWe found that PPP is not associated with the main genetic determinants of plaque psoriasis. Conversely, we identified genome-wide significant associations with theFCGR3A/FCGR3BandCCHCR1loci. We also observed 13 suggestive (P<5X10-6) susceptibility regions, including theIL4/IL13interval. Accordingly, we demonstrated a significant genetic correlation between PPP and Th2-mediated diseases like atopic dermatitis and ulcerative colitis. We also found that genes mapping to PPP-associated intervals were preferentially expressed in dendritic cells and enriched for T-cell activation pathways. Finally, we undertook a Mendelian randomization analysis, which supported a causal role of cigarette smoking in PPP.ConclusionsThe first genome-wide association study of PPP points to a pathogenic role for deregulated Th2 responses and cigarette smoking.Clinical implicationsThe results of the first PPP GWAS support the therapeutic potential of agents that inhibit Th2 responses and target inflammatory pathways activated by cigarette smoking.CapsuleThe genetic analysis of ∼1,400 PPP cases and 400,000 healthy controls points to a causal role of abnormal Th2 responses and cigarette smoking. This supports the therapeutic utility of Th2 inhibition.

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Efficacy and Safety of Brodalumab, an Anti-interleukin-17 Receptor A Monoclonal Antibody, for Palmoplantar Pustulosis: 16-Week Results of a Randomized Clinical Trial

Okubo,

Kobayashi,

Murakami

et al. 2024

Am J Clin Dermatol

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Background Palmoplantar pustulosis (PPP), a refractory skin disease characterized by repeated eruptions of sterile pustules and vesicles on palms and/or soles, involves interleukin-17 pathway activation. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, is being investigated for use in PPP treatment. Objective The aim was to assess the efficacy and safety of brodalumab in Japanese PPP patients with moderate or severe pustules/vesicles. Methods A phase 3, randomized, double-blind, placebo-controlled trial was conducted between July 2019 and August 2022, at 41 centers in Japan. Patients aged 18-70 years with a diagnosis of PPP for ≥ 24 weeks, a PPP Area Severity Index (PPPASI) score of ≥ 12, a PPPASI subscore of pustules/vesicles of ≥ 2, and inadequate response to therapy were included. Participants were randomized 1:1 to receive brodalumab 210 mg or placebo, subcutaneously (SC) at baseline, weeks 1 and 2, and every 2 weeks (Q2W) thereafter until week 16. Changes from baseline to week 16 in the PPPASI total score (primary endpoint) and other secondary skin-related endpoints and safety endpoints were assessed. Results Of the 126 randomized patients, 50 of 63 in the brodalumab group and 62 of 63 in the placebo group completed the 16-week period. Reasons for discontinuation were adverse event (n = 6), withdrawal by patient/parent/guardian (n = 3), progressive disease (n = 3), and lost to follow-up (n = 1) in the brodalumab group and Good Clinical Practice deviation (n = 1) in the placebo group. Change from baseline in the PPPASI total score at week 16 was significantly higher (p = 0.0049) with brodalumab (least-squares mean [95% confidence interval {CI}] 13.

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Optimal treatments and outcome measures of palmoplantar pustulosis: A systematic review and network meta‐analysis‐based comparison of treatment efficacy

Cited by 5 publications

References 52 publications

The role of B cells in systemic sclerosis

The role of B cells in systemic sclerosis

A genome-wide meta-analysis of palmoplantar pustulosis implicates Th2 responses and cigarette smoking in disease pathogenesis

Efficacy and Safety of Brodalumab, an Anti-interleukin-17 Receptor A Monoclonal Antibody, for Palmoplantar Pustulosis: 16-Week Results of a Randomized Clinical Trial

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