Psoriasis: a brief overview Raharja, Antony; Mahil, Satveer K; Barker, Jonathan N
Clinical medicine,
20/May , Letnik:
21, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Psoriasis is a clinically heterogeneous lifelong skin disease that presents in multiple forms such as plaque, flexural, guttate, pustular or erythrodermic. An estimated 60 million people have ...psoriasis worldwide, with 1.52% of the general population affected in the UK. An immune-mediated inflammatory disease, psoriasis has a major genetic component. Its association with psoriatic arthritis and increased rates of cardiometabolic, hepatic and psychological comorbidity requires a holistic and multidisciplinary care approach. Psoriasis treatments include topical agents (vitamin D analogues and corticosteroids), phototherapy (narrowband ultraviolet B radiation (NB-UVB) and psoralen and ultraviolet A radiation (PUVA)), standard systemic (methotrexate, ciclosporin and acitretin), biologic (tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors) or small molecule inhibitor (dimethyl fumarate and apremilast) therapies. Advances in the understanding of its pathophysiology have led to development of highly effective and targeted treatments.
Over recent years, significant progress has been made in characterisation of the underlying pathogenic mechanisms in psoriasis, a common cutaneous disease that is associated with major systemic ...co-morbidity and reduced life expectancy. Basic science discoveries have informed the design of novel therapeutic approaches, many of which are now under evaluation in late-stage clinical trials. Here we describe the complex interplay between immune cell types and cytokine networks that acts within self-perpetuating feedback loops to drive cutaneous inflammation in psoriasis. Genetic studies have been pivotal in the construction of the disease model and more recently have uncovered a distinct aetiology for rare, pustular variants of psoriasis. The translation of mechanistic insights into potential advancements in clinical care will also be described, including several treatments that target the interleukin-23 (IL-23)/T17 immune axis.
Psoriasis is a common inflammatory skin disease caused by the interplay between multiple genetic and environmental risk factors. This review summarises recent progress in elucidating the genetic ...basis of psoriasis, particularly through large genome-wide association studies. We illustrate the power of genetic analyses for disease stratification. Psoriasis can be stratified by phenotype (common plaque versus rare pustular variants), or by outcome (prognosis, comorbidities, response to treatment); recent progress has been made in delineating the genetic contribution in each of these areas. We also highlight how genetic data can directly inform the development of effective psoriasis treatments.
The routine use of targeted systemic immunomodulatory therapies has transformed outcomes for people with severe psoriasis, with skin clearance (clinical remission) rates up to 60% at 1 year of ...biologic treatment. However, psoriasis may recur following drug withdrawal, and as a result, patients tend to continue receiving costly treatment indefinitely. Here, we review research into the “inflammatory memory” in resolved psoriasis skin and the potential mechanisms leading to psoriasis recurrence following drug withdrawal. Research has implicated immune cells such as tissue resident memory T cells, Langerhans cells, and dermal dendritic cells, and there is growing interest in keratinocytes and fibroblasts. A better understanding of the interactions between these cell populations, enabled by single cell technologies, will help to elucidate the events underpinning the shift from remission to recurrence. This may inform the development of personalized strategies for sustaining remission while reducing long-term drug burden.
Psoriasis biologics: a new era of choice Mahil, Satveer K; Smith, Catherine H
The Lancet (British edition),
09/2019, Letnik:
394, Številka:
10201
Journal Article
Recenzirano
Blockade of IL-23 might cause a more durable, albeit slower, response since it places brakes on this self-amplifying inflammatory cascade at a more upstream point.7 The relative contribution of ...differential drug exposure will be uncovered in future analyses of concentrations of secukinumab and guselkumab in the serum. Biologic drugs offering superior longevity of response thus promise greater benefits for patients. Since the high costs of drug acquisition continue to limit use to those with more severe, recalcitrant psoriasis, a future challenge will be to secure wider and earlier access to these life-changing treatments. CHS is principal investigator on a Medical Research Council-funded consortium (PSORT) in psoriasis, whose industry partners include AbbVie, Sanquin, Qiagen, Pfizer, Novartis, MedImmune, Janssen, and Celgene, and on an Innovative Medicines Initiative-funded academia–industry consortium (BIOMAP) aimed at identifying biomarkers in psoriasis and atopic dermatitis, whose industry partners include Sanofi, LEO Pharma, Boehringer Ingelheim, Pfizer, and UCB Pharma.
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 healthy controls. Given the roll-out of extended interval vaccination programmes to maximise population coverage, we present findings after the first dose.
In this cohort study, we recruited consecutive patients with a dermatologist-confirmed diagnosis of psoriasis who were receiving methotrexate or targeted biological monotherapy (tumour necrosis factor TNF inhibitors, interleukin IL-17 inhibitors, or IL-23 inhibitors) from a specialist psoriasis centre serving London and South East England. Consecutive volunteers without psoriasis and not receiving systemic immunosuppression who presented for vaccination at Guy's and St Thomas' NHS Foundation Trust (London, UK) were included as the healthy control cohort. All participants had to be eligible to receive the BNT162b2 vaccine. Immunogenicity was evaluated immediately before and on day 28 (±2 days) after vaccination. The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as neutralising antibody responses to wild-type SARS-CoV-2, and spike-specific T-cell responses (including interferon-γ, IL-2, and IL-21) 28 days after vaccination.
Between Jan 14 and April 4, 2021, 84 patients with psoriasis (17 on methotrexate, 27 on TNF inhibitors, 15 on IL-17 inhibitors, and 25 on IL-23 inhibitors) and 17 healthy controls were included. The study population had a median age of 43 years (IQR 31–52), with 56 (55%) males, 45 (45%) females, and 85 (84%) participants of White ethnicity. Seroconversion rates were lower in patients receiving immunosuppressants (60 78%; 95% CI 67–87 of 77) than in controls (17 100%; 80–100 of 17), with the lowest rate in those receiving methotrexate (seven 47%; 21–73 of 15). Neutralising activity against wild-type SARS-CoV-2 was significantly lower in patients receiving methotrexate (median 50% inhibitory dilution 129 IQR 40–236) than in controls (317 213–487, p=0·0032), but was preserved in those receiving targeted biologics (269 141–418). Neutralising titres against the B.1.1.7 variant were similarly low in all participants. Cellular immune responses were induced in all groups, and were not attenuated in patients receiving methotrexate or targeted biologics compared with controls.
Functional humoral immunity to a single dose of BNT162b2 is impaired by methotrexate but not by targeted biologics, whereas cellular responses are preserved. Seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression. Real-world pharmacovigilance studies will determine how these findings reflect clinical effectiveness.
UK National Institute for Health Research.
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