Summary
Background
The use of recently introduced biologics targeting specific immune mechanisms has identified crucial steps in the pathogenesis of psoriasis. Studying the dynamics of changes of ...these target mechanisms in sequential skin biopsies during treatment with biologics may reveal potential biomarkers. Correlation between clinical parameters and the expression of specific genes during treatments may identify markers indicative of treatment response.
Objectives
This observational open‐label study aimed to provide an overview of important cell biological changes in lesional skin during treatment with adalimumab, and their relationship to clinical improvement.
Methods
Ten patients with moderate‐to‐severe plaque psoriasis were included and treated with adalimumab for 16 weeks. At baseline, and after 10 days and 16 weeks of treatment clinical scores were assessed and biopsies were taken to examine gene expression at the mRNA and protein level.
Results
The expression of marker genes for innate immunity, and epidermal differentiation and proliferation was rapidly restored to normal levels, whereas genes of the adaptive immune system showed a delayed decrease. The static and dynamic course of CD1a+ Langerhans cells and Ki67+ nuclei showed a significant strong correlation to the Psoriasis Area and Severity Index score. No correlation between interleukin‐17 expression and clinical scores was found.
Conclusions
The innate immune system is affected during adalimumab treatment well before the changes in the adaptive immune system become apparent. We may speculate that the addition of a treatment with an early effect on adaptive immunity to adalimumab may result in superior effectiveness compared with monotherapies.
What's already known about this topic?
Recently introduced biologics targeting specific immune mechanisms have identified crucial steps in the pathogenesis of psoriasis.
What does this study add?
During adalimumab treatment markers of epidermal differentiation, proliferation and the innate immune system revert rapidly to normal, well before changes in the adaptive immune system become apparent.
Clinical trials successfully using antibodies targeting IL-17 in psoriasis support the importance of IL-17 in the pathophysiology of this disease. However, there is a debate concerning the source and ...dynamics of IL-17 production in inflamed skin. Here we characterized IL-17-producing immune cells over time, using two established in vivo models of human skin inflammation that share many histological features with psoriasis, i.e., leukotriene B4 application and tape-stripping. Both treatments revealed a clear influx of neutrophils and T cells. Staining for IL-17 revealed that the majority of IL-17 was expressed by neutrophils and mast cells, in both models. Neutrophils, but not mast cells, coexpressed the IL-17-associated transcription factor RORγt and were able to form extracellular traps. While the presence of mast cells remained steady during the skin inflammatory process, the presence of neutrophils was clearly dynamic in time. Therefore, it is attractive to hypothesize that IL-17+/RORγt+ neutrophils contribute to human skin inflammation in vivo and possibly to the pathogenesis of skin diseases such as psoriasis. Surprisingly, T cells represented a minority of the IL-17-expressing cell population. These observations challenge the classical opinion that IL-17 is predominantly associated with T cells in skin inflammation.
Background
Psoriasis is a chronic inflammatory skin disease associated with quality of life (QoL) impairment. BRIDGE was a randomized, double‐blind, phase III study comparing the efficacy and safety ...of dimethylfumarate (DMF) with a fixed combination of fumaric acid esters (FAE) or placebo for the treatment of moderate‐to‐severe psoriasis.
Objectives
This post hoc analysis investigated treatment effect on QoL overall and by patient subgroups categorized by disease severity. Week 8 efficacy responses were also investigated as possible predictors of Week 16 Dermatology Life Quality Index (DLQI) outcomes.
Methods
Patients were randomized to receive a maximum daily dose of 720 mg of DMF, FAE (gradual up‐titration) or placebo for 16 weeks. Psoriasis Area Severity Index, Body Surface Area, Physician's Global Assessment and DLQI were assessed at baseline, Weeks 8 and 16. DLQI 0‐1 indicated ‘no effect on patient life’. Associations between baseline severity, Week 16 DLQI and Week 8 efficacy (as observed cases) were also examined.
Results
At baseline, 671 patients were included in the full analysis set (267 randomized to DMF, 273 to FAE and 131 to placebo). DMF was superior to placebo (P < 0.001) and not significantly different to FAE regarding Week 16 DLQI outcomes (P > 0.05). Baseline disease severity did not impact DLQI outcomes at Week 16. In DMF‐ and FAE‐treated patients, Week 8 PASI 50/75 responders reported better DLQI responses at Week 16 vs non‐responders (P < 0.05). Week 8 PASI ≤ 3 and/or PGA 0‐1 responders were also more likely to report DLQI 0‐1 at Week 16 vs non‐responders (P < 0.05).
Conclusion
Dimethylfumarate significantly improved DLQI outcomes vs. placebo and was not affected by baseline disease severity. Efficacy responses (PASI 50/75, PASI ≤3 and PGA 0‐1) as early as Week 8 were predictive of QoL outcomes at Week 16 in DMF‐ and FAE‐treated patients.
Treating older adults with psoriasis can be challenging owing to comorbidities, concomitant medication use, and consequent safety risks. Although many studies focus on the effectiveness and safety of ...systemic antipsoriatic therapies in the general population, their effectiveness in older adults with psoriasis has not been systematically assessed.
To evaluate the effectiveness and safety of systemic antipsoriatic therapies in patients 65 years or older.
A systematic literature search was conducted in Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) on November 11, 2019. No date limit was used. Randomized clinical trials, cohort studies, large case series, and meta-analyses assessing efficacy (or effectiveness) and/or safety of systemic antipsoriatic therapies in patients 65 years or older were included.
The initial search yielded 11 096 results, of which 31 unique articles with 39 561 patients were included in analysis. Overall, limited data were available per systemic agent, and overall quality of the included studies on conventional systemic therapies was low. At the end of the induction phase (12-16 weeks after start of treatment), a reduction of 75% in Psoriasis Area and Severity Index was achieved in 49% of 74 methotrexate sodium users 65 years or older, 46% to 52.6% of 178 older cyclosporin users, 27% to 47.8% of 108 older acitretin users, 15.6% to 64% of 256 etanercept users 65 years or older, 66.7% to 93% of 43 infliximab users 65 years or older, 60.7% to 65% of 100 adalimumab users 65 years or older, 56.5% of 46 ustekinumab users 65 years or older, and 86.4% of 67 secukinumab users 65 years or older. Effectiveness of acitretin, etanercept, adalimumab, and secukinumab appeared not to be associated with age; studies regarding other systemic antipsoriatic therapies did not provide age group comparisons. Older age was significantly associated with renal function deterioration in cyclosporin users and with lymphopenia in fumaric acid esters users (hazard ratio, 2.42; 95% CI, 1.65-3.55; P < .001). Infections were the most frequently reported adverse event in patients 65 years or older using biologics, but no significant association with age was found.
On the basis of limited available evidence, age alone should not be a limiting factor in psoriasis management. Awareness of comorbidities and concomitant medication use is very important, as well as appropriate dosing and frequent laboratory and clinical monitoring. More real-world evidence and (sub)analyses of prospective cohort studies on the effectiveness and safety of systemic therapies in older adults are critical to optimize personalized, effective, and safe antipsoriatic management in this growing patient group.
Summary
Background Psychological stressors might contribute to the severity of chronic inflammatory diseases such as psoriasis by dysregulating hypothalamic–pituitary–adrenal (HPA) axis activity.
...Objectives To evaluate the role of cortisol, a key component of the HPA axis, in reaction to psychological stress in patients with psoriasis.
Methods Serum cortisol, clinical indicators of disease severity (Psoriasis Area and Severity Index) and self‐report measures of daily stressors were measured monthly for 6 months in 62 patients with psoriasis.
Results In addition to the previous findings in this sample showing that peak levels of daily stressors predicted an increase in disease severity a month later, the peak levels of daily stressors were also significantly associated with a lower cortisol level. Moreover, patients who persistently experienced higher levels of daily stressors had lower mean cortisol levels than patients who experienced lower levels of daily stressors.
Conclusions Results suggest that daily stressors influence disease outcome in patients with psoriasis by affecting cortisol levels at moments of high stress. Furthermore, patients with persistently high levels of stressors seem to have a specific psychophysiological profile of lowered cortisol levels and may be particularly vulnerable to the influence of stressors on their psoriasis.
Background/Purpose
FibroTx Transdermal Analyses Patch (TAP) is a novel technology for non‐invasive measurements of protein biomarkers on the skin surface, in vivo. The aim of this study was to ...explore the potential of TAP in detecting skin surface biomarkers following mild perturbations, in vivo, using two experimental models: tape stripping, mimicking acute barrier disruption, and histamine iontophoresis, mimicking acute and local inflammation at minimal skin barrier insult.
Methods
Tape stripping and histamine iontophoresis were performed in two separate experiments on the volar forearm of healthy volunteers (n = 27 and n = 10, respectively). Biomarker levels were assessed with TAP at baseline and up to 72 h after stimulation. Functional (transepidermal water loss –TEWL– and a* value) and morphological (confocal reflectance microscopy –RCM) assessments were added in the tape stripping and histamine iontophoresis experiments, respectively.
Results
Cytokines IL‐1α and IL‐1RA and the antimicrobial peptide hBD‐1 showed distinct dynamics, despite substantial inter‐individual variation in levels, with an increase following tape stripping and a decrease following histamine iontophoresis. These dynamics could be related to the assessments made by TEWL and RCM. In the tape stripping experiment, additional biomarkers could be detected.
Conclusion
TAP measurements, especially IL‐1α, IL‐1RA, and hBD‐1, from the skin surface were sensitive enough for monitoring dynamic changes in the skin in the two models of skin perturbation. We conclude that TAP holds promise for non‐invasively unraveling the dynamics of processes related to skin perturbation and repair.
Summary
Background In dermatological research and clinical practice, there is a need for comprehensive self‐report instruments that assess a broad spectrum of health implications of chronic skin ...diseases, including generic and skin‐specific aspects of disease‐related quality of life. The advantages of dermatology‐specific, multidimensional instruments over generic instruments or single‐dimensional quality‐of‐life measures are in the detailed and specific information they provide about health areas that are affected by the skin condition and that may change through therapeutic intervention.
Objectives The development of a multidimensional health status inventory for chronic skin diseases (Impact of Chronic Skin Disease on Daily Life, ISDL) is described. The dermatology‐specific part of the inventory assesses dimensions of physical functioning, more specifically skin status, physical symptoms of itch, pain and fatigue and scratching responses as well as disease‐related stressors like stigmatization. The generic part gauges dimensions of psychological functioning, disease‐related impact, illness cognitions and social support by means of existing scales validated for other chronic diseases.
Methods Reliability and validity of the questionnaire were studied in various samples of patients with psoriasis and atopic dermatitis.
Results The ISDL showed high reliability and test–retest reliability in both patient groups. Convergent validity was indicated by moderate to strong correlations with other validated questionnaires. The scales proved sensitive to change both for dermatological ultraviolet B radiation therapy and cognitive behavioural treatment for itching.
Conclusion With its convincing results for reliability and validity the present evaluation supports the usefulness and applicability of the instrument for different chronic skin diseases.
Summary
Background EUROPSO (European Federation of Psoriasis Patient Associations) undertook a Europe‐wide survey examining quality of life and patients’ perspectives on treatment and their disease.
...Objectives To explore patients’ perspectives of psoriasis on their lifestyle and well‐being and to gain insight into the effectiveness of and satisfaction with currently available therapies for psoriasis.
Methods Self‐administered questionnaires (n = 50 500) were mailed to members of psoriasis patient associations in Belgium, the Czech Republic, Finland, France, Germany, Italy and the Netherlands.
Results Responses were received from 18 386 patients (36%), of whom 17 990 had psoriasis. Mean age at onset of psoriasis was 30·5 years, 59% of respondents had self‐reported moderate to severe psoriasis (3% or greater body surface area involvement) and 30% had been diagnosed with psoriatic arthritis. The mean Psoriasis Disability Index score was 12·2 (25% of the maximum score), increasing to 21 (44%) in patients with more than 10% body surface area involvement. The greatest impact was on activities of daily living, especially affecting clothing choice, bathing routine and sporting activities. Overall, 77% replied that psoriasis was a problem or a significant problem. While patients were satisfied with the information and care from their dermatologist (40% highly satisfied), available treatment options were less satisfactory, with over 70% reporting only low to moderate satisfaction.
Conclusions This is the largest survey of people with psoriasis in Europe and shows that psoriasis has a profound impact on quality of life.
Abstract
Psoriasis is an immune-mediated inflammatory disease (IMID) which may have a major impact on a patient's life, especially when the disease is moderate to severe. There is evidence that ...treatment of psoriasis during the first years is conservative and frequently based on topical agents which rarely clear lesions. Treatment with systemic agents including biologics is often undertaken only when topical agents have proved unsuitable, even in patients with moderate to severe disease. However, there is evidence that in other IMIDs (rheumatoid arthritis and Crohn's disease), targeted systemic treatment given early in the treatment pathway may improve long-term patient outcomes. We hypothesize that a patient-centered therapeutic approach, undertaken early in the psoriasis treatment pathway ("early intervention") with the goal of complete clearance, may improve control of cutaneous symptoms and may also modify disease course and burden. Critical points to address when designing an early intervention study would include: the definition of psoriasis disease activity; patient selection; intervention selection; and dosing strategies.
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