Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
292
result(s) for
"Burden, David"
Sort by:
Inhibition of the Interleukin-36 Pathway for the Treatment of Generalized Pustular Psoriasis
Seven patients with pustular psoriasis, three with mutations in
IL36RN
, were treated with a monoclonal antibody against interleukin-36 receptor and had amelioration of their skin disease.
Journal Article
Trial of Spesolimab for Generalized Pustular Psoriasis
In a randomized trial involving patients with the rare but disabling disorder generalized pustular psoriasis, the anti–interleukin-36 monoclonal antibody spesolimab greatly curtailed disease activity as compared with placebo over a period of 1 week. Systemic drug reactions and infections occurred with spesolimab.
Journal Article
Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR)
Drug survival reflects a drug’s effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09–1.37), being a current smoker (HR 1.19; 95% CI: 1.03–1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00–1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71–0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45–1.84) or infliximab (HR 1.56; 95% CI: 1.16–2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37–0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients.
Journal Article
The Battles of Hue
Recent years have seen increased interest in the professional use of wargames, and wargames are a potential tool to enable a better understanding of past urban conflicts and to plan for future urban security. Whilst access to professional wargames are limited, hobby wargames have been identified as useful and closely related areas to study. Previous work has identified around 214 manual hobby wargames that deal with urban conflict, but only 5 battles are covered by 5 or more wargames, and so provide a reasonable sample for comparative reviews. The Battle of Hue battle had many of the hallmarks of a modern urban battle, with both symmetric and asymmetric opposition, combined arms, a civilian and media presence, and the use of innovative technology. This article examines how 6 different wargame designers have approached the Battle of Hue, and how their design choices relate to the key characteristic of the Battle of Hue. The article also identifies where the principal deficiencies are. The article concludes by considering the issues highlighted by these games that wargaming has in representing urban conflict, and how these could be addressed in order to make wargaming a more useful tool to model urban conflict and security.
Journal Article
Targeting the IL-36 receptor with spesolimab mitigates residual inflammation and prevents generalized pustular psoriasis flares
People with generalized pustular psoriasis experience underlying skin inflammation, even in the absence of flares. Spesolimab treatment helps control the inflammation and prevent future flares.People with generalized pustular psoriasis experience underlying skin inflammation, even in the absence of flares. Spesolimab treatment helps control the inflammation and prevent future flares.
Journal Article
Psoriasis and Other Complex Trait Dermatoses: From Loci to Functional Pathways
Driven by advances in molecular genetic technologies and statistical analysis methodologies, there have been huge strides taken in dissecting the complex genetic basis of many inflammatory dermatoses. One example is psoriasis, for which application of classical linkage analysis and genome-wide association investigation has identified genetic loci of major and minor effect. Although most loci independently have modest genetic effects, they identify important biological pathways potentially relevant to disease pathogenesis and therapeutic intervention. In the case of psoriasis, these appear to involve the epidermal barrier, NF-κB mechanisms, and T helper type 17 adaptive immune responses. The advent of next-generation sequencing methods will permit a more detailed and complete map of disease genetic architecture, a key step in developing personalized medicine strategies in the clinical management of the complex inflammatory dermatoses.
Journal Article
Activating CARD14 Mutations Are Associated with Generalized Pustular Psoriasis but Rarely Account for Familial Recurrence in Psoriasis Vulgaris
Caspase recruitment family member 14 (CARD14, also known as CARMA2), is a scaffold protein that mediates NF-κB signal transduction in skin keratinocytes. Gain-of-function CARD14 mutations have been documented in familial forms of psoriasis vulgaris (PV) and pityriasis rubra pilaris (PRP). More recent investigations have also implicated CARD14 in the pathogenesis of pustular psoriasis. Follow-up studies, however, have been limited, so that it is not clear to what extent CARD14 alleles account for the above conditions. Here, we sought to address this question by carrying out a systematic CARD14 analysis in an extended patient cohort (n=416). We observed no disease alleles in subjects with familial PV (n=159), erythrodermic psoriasis (n=23), acral pustular psoriasis (n=100), or sporadic PRP (n=29). Conversely, our analysis of 105 individuals with generalized pustular psoriasis (GPP) identified a low-frequency variant (p.Asp176His) that causes constitutive CARD14 oligomerization and shows a significant association with GPP in Asian populations (P=8.4 × 10−5; odds ratio=6.4). These data indicate that the analysis of CARD14 mutations could help stratify pustular psoriasis cohorts but would be mostly uninformative in the context of psoriasis and sporadic PRP.
Journal Article
Study protocol of the global Effisayil 1 Phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare
IntroductionGeneralized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterised by recurrent flares of widespread neutrophilic aseptic skin pustular eruption. Despite the availability of approved biologics for GPP in Japan, Taiwan and Thailand, associated evidence is largely based on uncontrolled studies in which acute flares were not directly assessed. Therefore, there is a high unmet need to investigate new rapid-acting effective treatments that resolve symptoms associated with acute GPP flares. A prior Phase I proof-of-concept study showed rapid improvements in skin and pustule clearance with a single intravenous dose of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients presenting with an acute GPP flare. Here, we present the design and rationale of Effisayil 1, a global, Phase II, placebo-controlled study to evaluate the efficacy, safety and tolerability of spesolimab in patients presenting with an acute GPP flare.Methods and analysisAt least 51 patients with an acute GPP flare will be randomised 2:1 to receive a single 900 mg intravenous dose of spesolimab or placebo and followed for up to 28 weeks. The primary endpoint is a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0 or 1 (clear or almost clear) at Week 1. Safety will be assessed over the study duration by the occurrence of treatment-emergent adverse events. Blood and skin biopsies will be collected to assess biomarkers. Superiority of spesolimab over placebo in the proportion of patients achieving the primary and key secondary endpoints will be evaluated.Ethics and disseminationThe study complies with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation’s Good Clinical Practice and local regulations. Ethics committee approvals have been obtained for each centre from all participating countries and are listed in online supplementary file 1. Primary results will be published in a peer-reviewed journal.Trial registration detailsClinicalTrials.gov identifier: NCT03782792; Pre-results.
Journal Article