Palmoplantar pustular psoriasis (PPP) is a debilitating disease of the palms and/or soles that is resistant to treatment. Secukinumab, an anti–interleukin 17A monoclonal antibody, is highly ...efficacious in the treatment of moderate-to-severe psoriasis.
The primary objective was to determine the rate of achievement of a 75% improvement from baseline in Palmoplantar Psoriasis Area and Severity Index (PPPASI75) with secukinumab at week 16 versus with placebo (at a 2.5% significance level).
2PRECISE was a phase 3b multicenter, randomized, double-blind, placebo-controlled, parallel-group study comparing treatment with 300 mg of secukinumab (n = 79), 150 mg of secukinumab (n = 80), and placebo (n = 78) in subjects with moderate-to-severe PPP over a period of 52 weeks.
The primary end point was not met. At week 16, 26.6% of subjects treated with 300 mg of secukinumab achieved PPPASI75 versus 14.1% of those who received placebo (P = .0411) (odds ratio, 2.62; 95% confidence interval, 1.04-6.60). At week 52, 41.8% of subjects treated with 300 mg of secukinumab had achieved ppPASI75. More Dermatology Life Quality Index responses of 0 or 1 were achieved with 300 mg of secukinumab (13.0%) than with placebo (4.3%) at week 16. At week 52, 43.1% of subjects receiving 300 mg of secukinumab had a Dermatology Life Quality Index response of 0 or 1. No unexpected adverse events were observed.
Small sample size and characteristics of the PPP disease course.
Patients with PPP who were treated with secukinumab, 300 mg, showed benefit in terms of PPPASI75 responses over 52 weeks and improved quality of life.
The IL-36 pathway plays a key role in the pathogenesis of generalized pustular psoriasis (GPP). In a proof-of-concept clinical trial, treatment with spesolimab, an anti–IL-36 receptor antibody, ...resulted in rapid skin and pustular clearance in patients presenting with GPP flares.
We sought to compare the molecular profiles of lesional and nonlesional skin from patients with GPP or palmoplantar pustulosis (PPP) with skin from healthy volunteers, and to investigate the molecular changes after spesolimab treatment in the skin and blood of patients with GPP flares.
Pre- and post-treatment skin and blood samples were collected from patients with GPP who participated in a single-arm, phase I study (n = 7). Skin biopsies from patients with PPP (n = 8) and healthy volunteers (n = 16) were obtained for comparison at baseline. Biomarkers were assessed by RNA-sequencing, histopathology, and immunohistochemistry.
In GPP and PPP lesions, 1287 transcripts were commonly upregulated or downregulated. Selected transcripts from the IL-36 signaling pathway were upregulated in untreated GPP and PPP lesions. In patients with GPP, IL-36 pathway–related signatures, TH1/TH17 and innate inflammation signaling, neutrophilic mediators, and keratinocyte-driven inflammation pathways were downregulated by spesolimab as early as week 1. Spesolimab also decreased related serum biomarkers and cell populations in the skin lesions from patients with GPP, including CD3+ T, CD11c+, and IL-36γ+ cells and lipocalin-2–expressing cells.
In patients with GPP, spesolimab showed rapid modulation of commonly dysregulated molecular pathways in GPP and PPP, which may be associated with improved clinical outcomes.
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Lupus panniculitis is a rare manifestation of cutaneous lupus erythematosus, which may lead to major aesthetic sequelae with a severe impact on patients’ quality of life. We report 2 cases supporting ...the short- and long-term efficacy and safety of lipofilling in the treatment of lupus panniculitis-induced atrophy. These observations pave the way for prospective, larger-scale studies in patients with scarring lupus panniculitis, provided that the autoimmune pathogenic process is in complete, stable remission.
Background
Infliximab (IFX) is a chimeric immunoglobulin G‐1κ monoclonal antibody that neutralises the biologic activity of tumour necrosis factor‐α, and has shown efficacy (off‐label) for the ...treatment of severe hidradenitis suppurativa (HS). The relationship between clinical response and IFX pharmacokinetics (PK) in HS is currently unknown.
Objectives
To investigate the relationship between the trough serum concentration of IFX (TSI) and the clinical response to IFX in moderate‐to‐severe HS between 12th and 24th week (W12–W24) after IFX treatment onset.
Methods
We conducted a retrospective, monocentric study in a French dermatology tertiary care centre (Saint‐Louis hospital, Paris) between January 2013 and January 2022. Adult patients treated with IFX for moderate‐to‐severe HS were included if (i) they had at least one IFX serum dosage during follow‐up, and (ii) they had a measurable Hidradenitis Suppurativa Clinical Response (HiSCR) score between the 12th and 24th week (W12–W24). Patients received IFX infusions every 4, 6 or 8 weeks at 5, 7.5 or 10 mg/kg of body weight dosages.
Results
Twenty‐two patients (48.9%; median age: 36 31–43 years; 7 31.8% female) who had at least one IFX serum dosage between W12–W24 were enroled. The median TSI between W12 and W24 was significantly higher in the responding group compared to the nonresponding group of patients: 14.8 (12.1–15.7) versus 1.6 (0.8–3.5) µg/mL, respectively (p = 0.01). Using receiver operating characteristics (ROC) analysis curve, a TSI threshold of 7 µg/mL at W12–W24 showed sensitivity and specificity of 0.75 and 0.94, respectively.
Conclusions
This study supports some degree of correlation between clinical response and TSI in HS, and paves the way for prospective studies investigating correlations between PK, immunogenicity and clinical response in severe HS patients receiving IFX.
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