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Últimas publicaciones en Psoriasis Pustulosa Generalizada (PPG).

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Psoriasis pustulosa generalizada (PPG)

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Puig L, et al. Generalized pustular psoriasis: A global Delphi consensus on clinical course, diagnosis, treatment goals and disease management. J Eur Acad Dermatol Venereol. 2023.

Background: Generalized pustular psoriasis (GPP) is a rare and highly heterogeneous skin disease, characterized by flares of neutrophilic pustules and erythema. As a rare disease with few clinical studies and no standardized management approaches, there is a paucity of knowledge regarding GPP. Objectives: Conduct a Delphi panel study to identify current evidence and gain advanced insights into GPP. Methods: A systematic literature review was used to identify published literature and develop statements categorized into four key domains: clinical course and flare definition; diagnosis; treatment goals; and holistic management. Statements were rated on a Likert scale by a panel of dermatologists in two rounds of online questionnaires; the threshold for consensus was agreement by ≥80%. Results: Twenty-one panellists reached consensus on 70.9%, 61.8%, 100.0% and 81.8% of statements in the 'clinical course and flare definition', 'diagnosis', 'treatment goals' and 'holistic management of GPP' domains, respectively. There was clear consensus on GPP being phenotypically, genetically and immunologically distinct from plaque psoriasis. Clinical course is highly variable, with an extensive range of complications. Clinical and histologic features supporting GPP diagnosis reached high levels of agreement, and although laboratory evaluations were considered helpful for diagnosis and monitoring disease severity, there was uncertainty around the value of individual tests. All acute and long-term treatment goals reached consensus, including rapid and sustained clearance of pustules, erythema, scaling and crust, clearance of skin lesions and prevention of new flares. Potential triggers, associated comorbidities and differential diagnoses achieved low rates of consensus, indicating that further evidence is needed. Conclusions: Global consensus between dermatologists was reached on clinically meaningful goals for GPP treatment, on key features of GPP flares and on approaches for assessing disease severity and multidisciplinary management of patients. On this basis, we present a management algorithm for patients with GPP for use in clinical practice.
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Fukaura R, et al. Targeting IL-36 in Inflammatory Skin Diseases. BioDrugs. 2023.

Interleukin (IL)-36 cytokines are members of the IL-1 superfamily of cytokines. IL-36 cytokines are composed of three agonists (IL-36α, IL-36β, and IL-36γ) and two antagonists (IL-36 receptor antagonist [IL36Ra] and IL-38). These work in innate and acquired immunity and are known to contribute to host defense and to the pathogenesis of autoinflammatory diseases, autoimmune diseases, and infectious diseases. In the skin, IL-36α and IL-36γ are mainly expressed by keratinocytes in the epidermis, although they are also produced by dendritic cells, macrophages, endothelial cells, and dermal fibroblasts. IL-36 cytokines participate in the first-line defense of the skin against various exogenous assaults. IL-36 cytokines play significant roles in the host defense system and in the regulation of inflammatory pathways in the skin, collaborating with other cytokines/chemokines and immune-related molecules. Thus, numerous studies have shown IL-36 cytokines to play important roles in the pathogenesis of various skin diseases. In this context, the clinical efficacy and safety profiles of anti-IL-36 agents such as spesolimab and imsidolimab have been evaluated in patients with generalized pustular psoriasis, palmoplantar pustulosis, hidradenitis suppurativa, acne/acneiform eruptions, ichthyoses, and atopic dermatitis. This article comprehensively summarizes the roles played by IL-36 cytokines in the pathogenesis and pathophysiology of various skin diseases and summarizes the current state of research on therapeutic agents that target IL-36 cytokine pathways.
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Bellinato F, et al. Characteristics of Patients Experiencing a Flare of Generalized Pustular Psoriasis: A Multicenter Observational Study. Vaccines (Basel). 2023.

Background: Generalized pustular psoriasis (GPP) is a rare, severe inflammatory skin disease characterized by recurrent episodes of flares. Characteristics of patients experiencing a flare are hardly described in a real-life setting. The aim of the study is to investigate the clinical characteristics of patients experiencing a flare of GPP. Methods: Multicenter retrospective observational study on consecutive patients experiencing a flare of GPP between 2018 and 2022. Disease severity and quality of life were assessed by Generalized Pustular Psoriasis Area, Body Surface Area (BSA), and Severity Index (GPPASI), and Dermatology life quality index (DLQI) questionnaire, respectively. Visual analogue scale (VAS) of itch and pain, triggers, complications, comorbidities, pharmacological therapies, and outcome were collected. Results: A total of 66 patients, 45 (68.2%) females, mean age 58.1 ± 14.9 years, were included. The GPPASI, BSA, and DLQI were 22.9 ± 13.5 (mean ± standard deviation), 47.9 ± 29.1, and 21.0 ± 5.0, respectively. The VAS of itch and pain were 6.2 ± 3.3 and 6.2 ± 3.0, respectively. Fever (>38 °C) and leukocytosis (WBC > 12 × 109/L) were found in 26 (39.4%) and 39 (59.1%) patients, respectively. Precipitating triggers were identified in 24 (36.3%) and included infections (15.9%), drugs (10.6%), stressful life events (7.6%), and corticosteroids withdrawal (3.0%). Fourteen (21.2%) patients were hospitalized because of complications including infections in 9 (13.6%) leading to death in one case and hepatitis in 3 (4.5%). Conclusions: GPP flares can be severe and cause severe pain and itch with significant impact on the quality of life. In about one-third of patients the flare may have a persistent course and, with complications, lead to hospitalization.
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Patel PM, Sanchez-Melendez SN, Nambudiri VE. A narrative review of studies assessing the quality of life in patients with generalized pustular psoriasis. Exp Dermatol. 2023.

poor clinical prognosis, often resulting in severe systemic complications and mortality. The relapsing nature of the disease with recurrent or intermittent flares imposes a significant burden on patients' quality of life (QoL). Although inadequately studied, QoL data in GPP patients has been a recent point of investigation. We conducted a literature search on PubMed/MEDLINE using the following search terms: 'generalized pustular psoriasis' OR 'pustular psoriasis' AND 'quality of life'. We identified 12 relevant articles that provide insight into the large impact of GPP on the QoL of patients, the burden of the disease and the treatment, and the success of new treatment options in making a clinically important difference to QoL. This review illustrates a need for routine assessment of the QoL in interventional clinical trials for GPP and during physician encounters. This information can help guide clinicians on how to tailor the treatment approach from the patient's perspective or illustrate whether new therapies offer meaningful benefits to patient care as we enter an era of exciting new treatments for this challenging condition.
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Choon SE, et al. Diversity in the clinical presentation of generalized pustular psoriasis (GPP): A series of case vignettes from around the world. Exp Dermatol. 2023.

A key principle of clinical studies and case reports is that they should reflect the demographics and epidemiology of the patient population concerned. Here, we have compiled a diverse group of clinical cases of generalized pustular psoriasis (GPP) to showcase the differences in GPP presentation in patients worldwide. We attempt to capture the broad spectrum of clinical presentations of GPP and showcase the diversity of the patient population. The patients included in this series are diverse in age, genetic background, skin phototype and medical history. Moreover, they present with a variety of clinical courses of GPP and different degrees of systemic involvement, and experience flares triggered by different inciting factors. The key learnings from this case series may support physicians in identifying and managing patients with this rare and multifaceted disease that can affect patients both physically and psychologically.
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Ericson O, et al. Mortality in generalized pustular psoriasis: A population-based national register study. J Am Acad Dermatol. 2023.

No abstract available.
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Burden AD, et al. The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score: online assessment and validation study of a specific measure of GPP disease activity. Br J Dermatol. 2023.

No abstract available.
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Jaworecka K, et al. Characteristics of pruritus in various clinical variants of psoriasis: Final report of the binational, multicentre, cross-sectional study. J Eur Acad Dermatol Venereol. 2023.

Background: Pruritus, which is the most frequent subjective symptom of psoriasis, may cause significant discomfort, embarrassment and even interfere with patients normal daily activities. However, the perception of itch in various psoriasis subtypes remains unknown. Objectives: The aim of this study was to investigate and to characterize pruritus in different clinical variants of psoriasis. Methods: This cross-sectional, binational, multicentre study included 295 subjects suffering from nine different clinical subtypes of psoriasis: large-plaque psoriasis (n = 45), nummular psoriasis (n = 32), guttate psoriasis (n = 31), scalp psoriasis (n = 32), inverse psoriasis (n = 23), erythrodermic psoriasis (n = 33), palmoplantar psoriasis vulgaris (n = 33), palmoplantar pustular psoriasis (n = 42) and generalized pustular psoriasis (n = 23). Measures included sociodemographic and anthropometric data, detailed pruritus characteristics including but not limited to pruritus intensity, frequency and extend, as well as psoriasis severity. Results: The lifetime prevalence of pruritus in each clinical variant of psoriasis was similar and quite high, reaching up to 100% in some disease subtypes (i.e., nummular psoriasis, scalp psoriasis and generalized pustular psoriasis). Psoriasis severity correlated with pruritus intensity in scalp psoriasis, palmoplantar pustular psoriasis and generalized pustular psoriasis. The age, duration of psoriasis and BMI did not interfere with the intensity of itch. Conclusions: Pruritus is highly prevalent in each clinical variant of psoriasis. However, the sensation of itch is very individual, difficult to universally describe even in the same subtype.

Tratamiento para la PPG

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Burden AD. Spesolimab, an interleukin-36 receptor monoclonal antibody, for the treatment of generalized pustular psoriasis. Expert Rev Clin Immunol. 2023.

Introduction: Generalized pustular psoriasis (GPP) is a rare cutaneous and systemic inflammatory disease which is characterized by flares of widespread painful pustulation of the skin, often associated with fever and elevated inflammatory markers. Although it has historically been regarded as a severe variant of plaque psoriasis, genetic and immunological developments over the past decade have revealed that it is a distinct auto-inflammatory entity, in which over-activity of the interleukin-36 signaling pathway is fundamental. Treatments targeting the IL-36 pathway are under investigation, and in 2022 spesolimab, a monoclonal antibody against the IL-36 receptor, was licensed for treating flares of GPP. Areas covered: In this review I discuss the epidemiology, clinical features, genetics, patho-mechanisms, and current treatment options for GPP. I describe the results of clinical trials that led to the licensing of spesolimab for flares of GPP. Expert opinion: The marked efficacy of spesolimab in GPP opens a new era of highly effective, scientifically-rational, and evidence-based treatment for this orphan disease, and has implications for other diseases in which interleukin 36 signaling is involved.
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Elewski BE, et al. Rapid and sustained improvements in Generalized Pustular Psoriasis Physician Global Assessment scores with spesolimab for treatment of generalized pustular psoriasis flares in the randomized, placebo-controlled Effisayil 1 study. J Am Acad Dermatol. 2023.

Background: Effisayil 1 was a randomized, placebo-controlled study of spesolimab, which is an anti-IL-36 receptor antibody, in patients presenting with a generalized pustular psoriasis flare. Objective: To assess the effects of spesolimab over the 12-week study. Methods: The primary endpoint of the study was Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at week 1. Patients (N = 53) were randomized (2:1) to receive a single intravenous dose of 900 mg spesolimab or placebo on day 1. Patients could receive open-label spesolimab for persistent flare symptoms on day 8. Results: Most patients receiving spesolimab achieved a GPPGA pustulation subscore of 0 (60.0%) and GPPGA total score of 0 or 1 (60.0%) by week 12. In patients randomized to placebo who received open-label spesolimab on day 8, the proportion with GPPGA pustulation subscore of 0 increased from 5.6% at day 8 to 83.3% at week 2. No factors predictive of spesolimab response were identified in patient demographics or clinical characteristics. Limitations: The effect of initial randomization was not determined conventionally beyond week 1 due to patients receiving open-label spesolimab. Conclusion: Rapid control of generalized pustular psoriasis flare symptoms with spesolimab was sustained over 12 weeks, further supporting its potential use as a therapeutic option for patients.
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Burden AD, et al. Efficacy of spesolimab for the treatment of generalized pustular psoriasis flares across pre-specified patient subgroups in the Effisayil 1 study. Exp Dermatol. 2023.

Effisayil 1 was a multicentre, randomized, double-blind, placebo-controlled study of the anti-interleukin (IL)-36 receptor monoclonal antibody, spesolimab, in patients presenting with a generalized pustular psoriasis (GPP) flare. Previously published data from this study revealed that within 1 week, rapid pustular and skin clearance were observed in patients receiving spesolimab versus placebo. In this pre-specified subgroup analysis, the efficacy of spesolimab was evaluated according to patient demographic and clinical characteristics at baseline in patients receiving spesolimab (n = 35) or placebo (n = 18) on Day 1. Efficacy was by assessed by achievement of primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0 at Week 1) and key secondary endpoint (GPPGA total score of 0 or 1 at Week 1). Safety was assessed at Week 1. Spesolimab was found to be efficacious and had a consistent and favourable safety profile in patients presenting with a GPP flare, regardless of patient demographics and clinical characteristics at baseline.
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Navarini AA, et al. Spesolimab improves patient-reported outcomes in patients with generalized pustular psoriasis: Results from the Effisayil 1 study. J Eur Acad Dermatol Venereol. 2023.

Background: Generalized pustular psoriasis (GPP) is a rare inflammatory skin disease with a considerable clinical burden. In the EffisayilTM 1 study, spesolimab, an anti-interleukin-36 receptor monoclonal antibody, demonstrated efficacy in treating GPP flares. Objectives: To evaluate patient-reported outcomes (PROs) of patients with GPP who were treated with intravenous (IV) spesolimab 900 mg in the EffisayilTM 1 study. Methods: Fifty-three patients presenting with a GPP flare were randomized (2:1) to receive a single dose of IV spesolimab 900 mg or placebo and were followed for 12 weeks. Four PROs (pain visual analogue scale [pain VAS]; Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]; Dermatology Life Quality Index [DLQI]; and Psoriasis Symptom Scale [PSS]) were assessed throughout the 12-week study. Minimal clinically important differences (MCIDs) were defined. All data are reported descriptively. Results: In patients who received spesolimab, improvements from baseline (median [Q1, Q3]) were observed in pain VAS (-21.3 [-55.3, -3.1]), FACIT-Fatigue (7.0 [1.0, 20.0]), DLQI (-2.5 [-8.0, 1.0]) and PSS (-4.0 [-7.0, 0.0]) within 1 week of treatment. These improvements were sustained over 12 weeks and corresponded to the achievement of MCIDs at Week 1, which were also sustained over 12 weeks. Patients in the placebo arm experienced improvements in PROs and achievement of MCIDs after receipt of open-label spesolimab at Week 1. Conclusions: Patients with a GPP flare treated with spesolimab achieved improvements in PROs by Week 1, which were sustained for 12 weeks, and achieved MCIDs as early as Week 1.
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Warren RB, et al. Imsidolimab, an Anti-IL-36 Receptor Monoclonal Antibody for the Treatment of Generalised Pustular Psoriasis: Results from the Phase 2 GALLOP Trial. Br J Dermatol. 2023.

Background: Generalised pustular psoriasis (GPP) is a systemic inflammatory disease that can be severe, debilitating, and life-threatening. Uncontrolled activation of interleukin-36 (IL-36) pro-inflammatory activity may underlie the pathogenesis of GPP. Currently, GPP-specific treatment options are limited. Objectives: To evaluate the efficacy and safety of the anti-IL-36 receptor antibody imsidolimab in subjects with GPP. Methods: In an open-label, single-arm, multiple-dose study, subjects with GPP were treated with imsidolimab to assess clinical efficacy, tolerability, and safety. Subjects received an intravenous (IV) imsidolimab 750 mg dose on Day 1, followed by 3 doses of subcutaneous (SC) imsidolimab 100 mg administered on Days 29, 57, and 85. The primary efficacy endpoint was the proportion of subjects that achieved a clinical response at Week 4 and Week 16 following treatment with imsidolimab as measured by the Clinical Global Impression (CGI) scale. Results: A total of 8 patients were enrolled and 6 subjects completed the study. Responses were observed as early as Day 3, most rapidly for pustulation relative to other manifestations of GPP, with continued and consistent improvement across multiple efficacy assessments at Day 8, Day 29, and through Day 113. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. No subject discontinued the study due to a non-serious TEAE. Two subjects experienced serious adverse events (SAEs) and no deaths were reported. Conclusions: Imsidolimab demonstrated a rapid and sustained resolution of symptoms and pustular eruptions in subjects with GPP. It was generally well-tolerated, associated with acceptable safety, and is advancing to Phase 3 trials. These data support targeting of IL-36 signalling with a specific antibody, imsidolimab, as a therapeutic option for this severely debilitating condition. The study was registered under EudraCT Number 2017-004021-33 and NCT03619902.

 

 

PC-ES-111082

 

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