Catherine Smith

King's College London | KCL · St John's Institute of Dermatology

Serum adalimumab concentration is a biomarker of treatment response but therapeutic drug monitoring (TDM) is yet to be implemented in routine psoriasis care. We incorporated adalimumab TDM in a national specialised psoriasis service and evaluated it using the RE-AIM implementation science framework. We undertook pre-implementation planning (validat...

Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribu...

Objectives To investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). Methods Demographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A thr...

Biologic therapies for psoriasis can cause paradoxical eczema. The role of genetic factors in its pathogenesis are unknown. To identify risk variants, we conducted a genome-wide association study (GWAS) of 3212 psoriasis patients, of whom 88 developed paradoxical eczema. Two lead single nucleotide polymorphisms (SNPs) reached genome-wide significan...

Background Real-world data evaluating effectiveness and persistence of systemic therapies for patients with psoriasis are limited. Objectives To determine the effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters (FAEs) and methotrexate in patients with moderate-to-severe psoriasis. Methods Data from The British Association...

Background Non-adherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association betwee...

Background Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness. However, factors associated with mental illness are unclear. Objectives To synthesise and evaluate all available evidence on factors associated with depression, anxiety, and severe mental illness (SMI) among adults with AE or psoriasis. Methods...

Objectives: Obesity is a common (30%-40%) comorbidity of psoriasis. Weight loss is shown to improve the severity of psoriasis; however, little is known about the factors that may influence successful weight loss in the context of obesity and psoriasis. The current qualitative study aimed to explore the obesity-associated beliefs, perceptions, and...

Purpose of Review SARS-CoV-2 has had a devastating global effect, with vaccinations being paramount in the public health strategy against COVID-19. Vaccinations have uncoupled infection from adverse COVID-19 outcomes worldwide. While immune-modifying therapies are effective for the management of skin diseases such as psoriasis and atopic dermatitis...

Background: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. Objec...

Background: The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modi...

Background: Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare. Objectives: To perform a scoping review to identify and catalogue candidate biomarkers of syst...

Objectives: Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. The objective was to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the perfor...

Background Palmoplantar pustulosis (PPP) is a severe inflammatory skin disorder, characterised by eruptions of painful, neutrophil-filled pustules on the palms and soles. While PPP has a profound effect on quality of life, it remains poorly understood and notoriously difficult to treat. Objective We sought to investigate the immune pathways that u...

Background: Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice. Objectives: To i...

Background: High body weight is common in psoriasis and is associated with depression and anxiety. Past studies are mostly cross-sectional and may underestimate the role of demographic and illness-related factors in the association between mental health and body weight in psoriasis. Objectives: This study explored the association between depress...

Background Palmoplantar pustulosis is a rare, debilitating, chronic skin disease involving the hands and feet, and there are limited treatment options. Mechanistic findings suggest that interleukin 1 may be a pathogenic driver. Objective To determine whether or not anakinra [Sobi (Swedish Orphan Biovitrum AB), Stockholm, Sweden], an interleukin 1...

Background COVID-19 vaccination is efficacious at protecting against severe COVID-19 outcomes in the general population. However, vaccine hesitancy (unwillingness for vaccination despite available vaccination services) threatens public health. Individuals taking immunosuppression for psoriasis have been prioritised for COVID-19 vaccination, however...

We believe that there is significant interest in the role of IL‐1 in the pathomechanism of palmoplantar pustulosis. However, the APRICOT study failed to demonstrate a therapeutic effect of the IL‐1 receptor antagonist. So, we recommend that the authors perform an additional subgroup analysis based on the presence or absence of plaque psoriasis.

In view of the growth of clinical risk prediction models using genetic data, there is an increasing need for studies that use appropriate methods to select the optimum number of features from a large number of genetic variants with a high degree of redundancy between features due to linkage disequilibrium (LD). Filter feature selection methods base...

Biologic therapies have transformed the management of psoriasis, but clinical outcome is variable leaving an unmet clinical need for predictive biomarkers of response. Here we perform in-depth immunomonitoring of blood immune cells of 67 patients with psoriasis, before and during therapy with the anti-TNF drug adalimumab, to identify immune mediato...

Background COVID-19 vaccines have robust immunogenicity in the general population. However, data for individuals with immune-mediated inflammatory diseases who are taking immunosuppressants remains scarce. Our previously published cohort study showed that methotrexate, but not targeted biologics, impaired functional humoral immunity to a single dos...

The identification of robust endotypes – disease subgroups of clinical relevance – is fundamental to stratified medicine. We hypothesised that HLA-C*06:02 status, the major genetic determinant of psoriasis, defines a psoriasis endotype of clinical relevance. Using two UK-based cross-sectional datasets – an observational severe psoriasis study (Biom...

Importance: Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. Objective: To examin...

Background The increase in the number of available biologic agents for psoriasis has led to an urgent need to evaluate their associated risk of serious infections to help inform clinical decisions. Methodology We systematically searched PubMed, Medline, Embase, and Cochrane databases for biologics targeting TNF (adalimumab, etanercept, infliximab,...

Background Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease affecting the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. Objective To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit for PPP. Methods A rando...

Background Patients on therapeutic immunosuppressants for immune-mediated inflammatory diseases were excluded from COVID-19 vaccine trials. We therefore aimed to evaluate humoral and cellular immune responses to COVID-19 vaccine BNT162b2 (Pfizer-BioNTech) in patients taking methotrexate and commonly used targeted biological therapies, compared with...

Indirect excess morbidity in the COVID‐19 pandemic may arise from public health risk‐mitigation efforts such as stay‐at‐home orders and re‐purposing of healthcare services1. Increased mental health disorders and shortfalls in the care of long‐term conditions are described.

Dear Editor, BIOMAP (BIOMarkers in Atopic dermatitis and Psoriasis) is a large European consortium aiming to advance personalised medicine for atopic dermatitis and psoriasis by identifying biomarkers which predict therapeutic response and disease progression. BIOMAP brings together clinicians, researchers, patient organisations and pharmaceutical...

Background Atopic dermatitis (AD) is a common skin condition with a prevalence of 2–10% in adults ¹ . IL-4 and IL-13 play a key role in the pathogenesis. Dupilumab, a human IgG 4 monoclonal antibody binding the alpha subunit of the IL-4 receptor, blocking IL-4 and IL-13 signaling, has important efficacy in this difficult to treat disease. We first...

Background New technologies have enabled the potential for stratified medicine in psoriasis. It is important to understand patients’ preferences to enable the informed introduction of stratified medicine which is likely to involve a number of individual tests that could be collated into a prescribing‐algorithm for biologic selection to be used in c...

DUPILUMAB-INDUCED ENTHESITIS/ARTHRITIS IN PATIENTS WITH ATOPIC DERMATITIS: A RETROSPECTIVE OBSERVATIONAL STUDY

Background Indirect excess morbidity has emerged as a major concern in the COVID-19 pandemic. People with psoriasis may be particularly vulnerable to this because of prevalent anxiety and depression, multimorbidity and therapeutic use of immunosuppression. Objective Characterise the factors associated with worsening psoriasis in the COVID-19 pandem...

During the COVID-19 pandemic, rapid, real-world evidence is essential for the development of knowledge and subsequent public health response. In dermatology, provider-facing and patient-facing registries focused on COVID-19 have been important sources of research and new information aimed at guiding optimal patient care. The 7 dermatology registrie...

Background The effectiveness and cost‐effectiveness of biologic therapies for psoriasis are significantly compromised by variable treatment responses. Thus, more precise management of psoriasis is needed. Objectives We aim to identify subgroups of psoriasis patients treated with biologic therapies, based on changes in their disease activity over t...

High-quality dermatology patient registries often require considerable time to develop and produce meaningful data. Development time is influenced by registry complexity and regulatory hurdles that vary significantly nationally and institutionally. The rapid emergence of the COVID-19 global pandemic has challenged health services in an unprecedente...

A cohort study of patients with moderate‐severe psoriasis registered to the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) determined that there was no association between developing a first basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) following treatment with biologic therapy when compared to...

Importance: The emerging paradigm of treat-to-target in psoriasis requires accurate monitoring of treatment response. The commonly used physician global assessment tool does not capture the patient's perception of their disease. Patient assessments facilitate shared decision-making and foster patient-centered care; however, recent research reports...

A stratified medicine approach for the treatment of psoriasis promises greater certainty of clinical decision making through prediction of response based on clinical, pharmacological, and -omics data from an individual patient. As yet, there is no predictive model for treatment response in routine clinical use for psoriasis. The Psoriasis Stratific...

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arth...

Objectives Registry data suggest that people with immune‐mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse COVID‐19 outcomes compared to patients receiving no systemic treatments. We used international patient survey data to explore the hypothesis that greater risk‐mitigating behaviour in those receivin...

Importance Treatments for psoriasis may be less effective in everyday practice than in clinical trials. Emulating a target trial using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) can provide treatment effect estimates that are robust and can inform both clinicians and regulatory bodies. Obje...

Background: Current treatment options for Palmoplantar Pustulosis (PPP), a debilitating chronic skin disease which affects the hands and feet, are limited. The Anakinra for Pustular psoriasis: Response in a Controlled Trial (APRICOT) aims to determine the efficacy of anakinra in the treatment of PPP. This article describes the statistical analysis...

Introduction Evidence indicates that people with the common inflammatory skin diseases atopic eczema or psoriasis are at increased risk of mental illness. However, the reasons for the relationship between skin disease and common mental disorders (ie, depression and anxiety) or severe mental illnesses (ie, schizophrenia, bipolar disorder and other p...

The Aryl hydrocarbon Receptor (AHR) is an environmental sensor and transcription factor activated by a variety of man-made and natural ligands, which has recently emerged as critical regulator of homeostasis at barrier organs such as the skin. Activation of the AHR pathway down-modulates skin inflammatory responses in animal models and psoriasis cl...

Objective To determine the risk of a diagnosis of osteoarthritis (OA) in psoriatic arthritis (PsA) patients compared to patients with psoriasis and a general population cohort. Methods Incident PsA patients aged 18-89 years at diagnosis were identified from the UK Clinical Practice Research Datalink between 1998 and 2014. All PsA patients were mat...

Biological therapies have transformed the management of psoriasis but clinical outcome is variable leaving an unmet clinical need for predictive biomarkers of response. To identify the immune determinants of response to the anti-TNF drug adalimumab and evaluate their predictive value, we performed in-depth immunomonitoring of blood immune cells of...

Objectives Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse COVID-19 outcomes compared to patients receiving no systemic treatments. We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receivin...

This evidence‐ and consensus‐based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The first part of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline. Sug...

Dupilumab (Dupixent®) is the first biologic drug licensed for treatment of adults with atopic dermatitis (AD). Data regarding its long‐term real‐world effectiveness and tolerability are limited. We report comprehensive outcome data at one year for the first 100 adult patients initiated on dupilumab in a specialist eczema clinic (May 2017‐November 2...

The aim of this guideline is to provide an update on evidence-based recommendations for treatment of adult patients with PsA. The previous BSR guidelines for PsA were published in 2012 and since that time, there have been many new advanced therapies licensed for PsA. This update will provide practical guidance for clinicians on the optimal selectio...

With biologic drugs dominating the therapeutic space for severe immune-mediated inflammatory disease, it is critical for clinicians to be familiar with the concept of drug immunogenicity, with the potential for our patients to develop anti-drug antibodies (ADA) of clinical relevance. Whilst there are clear differences between different therapeutic...

Background The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited. Objective Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization....