Search

Introduction In the real-world APPRECIATE study (NCT02740218), most patients with psoriasis demonstrated notable improvements on disease severity measures and reported clinically meaningful treatment benefits with apremilast. Objective We aim to further describe patient-relevant needs and benefits and patient satisfaction with apremilast, including subgroup analyses based on patient characteristics. Methods APPRECIATE, a multinational, retrospective, cross-sectional study, enrolled patients with chronic plaque psoriasis who started apremilast according to the European label. Patient Benefit Index (PBI; range 0 (no patient-relevant benefit) to 4 (maximum patient-relevant benefit), global PBI score ≥ 1 indicating minimum patient-relevant benefit and ≥ 3 indicating high benefit) and nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9; range 0–100) were assessed 6 (± 1) months after apremilast initiation and summarized descriptively. Relationships between global PBI and TSQM-9 assessments were analyzed by Pearson correlations. Results Of 480 enrolled patients, 347 (72.3%) had remained on apremilast at 6 (± 1) months; 90.9% (300/330) achieved global PBI score ≥ 1. Mean (standard deviation) global PBI score was 2.8 (1.2). Higher achievement of global PBI score ≥ 3 was observed in patients with no prior treatments (61.1% (22/36)) or prior phototherapy (64.6% (42/65)) versus prior conventional systemic (54.4% (100/184)) or biologic (38.6% (17/44)) treatment. Strong correlations were observed between the global PBI score and the TSQM-9 global satisfaction and effectiveness subscale scores. Conclusion Patients continuing apremilast for 6 (± 1) months in APPRECIATE reported patient-relevant treatment benefits. Findings suggest that receiving apremilast earlier versus later in treatment management is consistent with greater improvements in patient-relevant treatment outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00628-3.

In adults with atopic dermatitis (AD), head and/or neck involvement is frequent, bothersome, and impacts quality of life, however, long-term topical corticosteroids (TCS) are contraindicated for this difficult-to-treat region. Baricitinib, an oral, selective, reversible inhibitor of Janus kinase 1/2 has demonstrated efficacy in adult patients with moderate-to-severe AD.For this post hoc analysis, data from five Phase III trials were used to investigate the efficacy of baricitinib in patients with head and neck involvement.Data were obtained from BREEZE-AD1, -AD2, -AD4, -AD5, and -AD7; Phase III, multicenter, randomized, double-blind, placebo-controlled studies conducted in patients ≥18 years with moderate-to-severe AD. BREEZE-AD1, -AD2, and -AD5 evaluated baricitinib as monotherapy, and BREEZE-AD4 and -AD7 evaluated baricitinib in combination with TCS, topical calcineurin inhibitors, or topical PDE-4 inhibitors, where available. The proportion of patients with improvement of Eczema Area and Severity Index (EASI) total score from baseline of ≥50% (EASI50) and ≥75% (EASI75), as well as head/neck EASI50 and EASI75 and erythema head/neck EASI50 and EASI75 response rates were assessed up to Week 16.Across the studies, 93-98% of patients had head/neck involvement at baseline (EASI head/neck score ≥1). Baricitinib was similarly effective based on EASI total score for the entire body in all studies. In the monotherapy studies, the proportion of patients achieving head/neck EASI50 and EASI75 scores was significantly higher for baricitinib 2-mg and 4-mg versus placebo at Weeks 1 and 16.Baricitinib 2-mg and 4-mg treatment showed rapid and substantial reduction in AD head and neck severity, including erythema.

Background: Depression is overrepresented in psoriasis. However, it is not clear whether the presence of psoriatic arthritis (PsA) independently increases patients' depressive burden. Furthermore, current evidence regarding suicidality risk of psoriasis populations is conflicting, and the role of PsA in suicidality outcomes of psoriasis is unknown. Objectives: (i) To test whether PsA is associated with depression and lifetime suicidal ideation among patients with psoriasis; (ii) to capture different suicidal phenomena in these patients; and (iii) to investigate whether suicidality and depressive symptom severity are associated with clinical markers of psoriasis severity and chronicity. Methods: A cross-sectional survey of tertiary patients (n = 219, aged 18–65 years) with dermatologist-confirmed chronic plaque psoriasis, of whom 84 had rheumatologist-confirmed PsA, was undertaken. The Hospital Anxiety and Depression Scale and Sheehan-Suicidality Tracking Scale were used to assess depression and lifetime suicidality, respectively. Results: PsA presence was associated with depression in patients with psoriasis, independent of other physical comorbidities (adjusted odds ratio 2.92, 95% confidence interval 1.53–5.68). Furthermore, patients with PsA experienced significantly higher levels of anhedonia and anxiety, after controlling for psychiatric history. Of all participants, 48.8% reported lifetime suicidal ideation with or without intent, 21.3% reported suicidal planning, and 9.4% reported suicide attempts. Lifetime suicidality prevalence did not differ between patients with and without PsA. Depressive symptom severity and lifetime suicidality scores were not associated with objective measures of psoriasis severity or treatment group. Conclusions: These data suggest that joint involvement in psoriasis is associated with higher depressive burden. There is a need for routine depression screening among patients with psoriasis, particularly when PsA is present. Anhedonia appears to be a particularly relevant symptom in the depression phenotype of this population. We did not find a statistically significant association between PsA and suicidality. Nevertheless, suicidality rates in tertiary patients with psoriasis appear to be higher than those in the general population. Suicidality monitoring is recommended to help in reducing future psychiatric morbidity and mortality in patients with psoriasis.

Background\ud\udThe quality of dermatology consultations is partly determined by how clinicians approach patient care. The term ‘Personal Models’ describes the explanatory frameworks of thoughts, feelings and experiences that drive behaviour. One study found that clinicians’ personal models, specifically their beliefs about autonomy and patient self-management, influenced the degree to which clinicians engage patients in shared decision-making during consultations. Further research is needed to further explore how clinicians’ personal models inform and affect the quality of patient care.\udAims & objectives\ud\udTo explore how clinicians’ personal models inform shared decision-making and consultation style in managing people living with psoriasis in the context of a new treatment, Apremilast.\udMethods\ud\udA Framework Analysis of qualitative semi-structured telephone interviews with 13 dermatologists from the UK and Germany who participated in a novel medicine trial for psoriasis called APPRECIATE.\udResults\ud\udTwo themes were derived from the data. Theme one, personal working models of patient care, comprised of two sub-themes: (1.1) patient-centeredness: a continuum; and (1.2) stereotypes and assumptions. Theme two, impact of personal working models on patient care, included three sub-themes: (2.1) shared decision-making: a continuum; (2.2) consultation skills; and (2.3) impact of concerns about Apremilast on prescribing behaviour.\udConclusions\ud\udAlthough many dermatologists endorsed a patient-centred approach, not all reported working in this way. Clinicians’ personal models, their beliefs, stereotypes, personal perceptions, and assumptions about patients, are likely to affect their prescribing behaviour and shared decision-making. Additional specialised training and education could increase patient-centeredness and whole person management.

Importance: People diagnosed with psoriasis have an increased risk of premature mortality, but the underlying reasons for this mortality gap are unclear.Objective: To investigate whether patients with psoriasis have an elevated risk of alcohol-related mortality.Design, Setting, and Participants: An incident cohort of patients with psoriasis aged 18 years and older was delineated for 1998 through 2014 using the Clinical Practice Research Datalink (CPRD) and linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records. Patients with psoriasis were matched with up to 20 comparison patients without psoriasis on age, sex, and general practice.Main Outcomes and Measures: Alcohol-related deaths were ascertained via the Office for National Statistics mortality records. A stratified Cox proportional hazard model was used to estimate the cause-specific hazard ratio for alcohol-related death, with adjustment for socioeconomic status.Results: The cohort included 55 537 with psoriasis and 854 314 patients without psoriasis. Median (interquartile) age at index date was 47 (27) years; 408 230 of total patients (44.9%) were men. During a median (IQR) of 4.4 (6.2) years of follow-up, the alcohol-related mortality rate was 4.8 per 10 000 person-years (95% CI, 4.1-5.6; n = 152) for the psoriasis cohort, vs 2.5 per 10 000 (95% CI, 2.4- 2.7; n = 1118) for the comparison cohort. The hazard ratio for alcohol-related death in patients with psoriasis was 1.58 (95% CI, 1.31-1.91), and the predominant causes of alcohol-related deaths were alcoholic liver disease (65.1%), fibrosis and cirrhosis of the liver (23.7%), and mental and behavioral disorders due to alcohol (7.9%).Conclusions and Relevance: People with psoriasis have approximately a 60% greater risk of dying due to alcohol-related causes compared with peers of the same age and sex in the general population. This appears to be a key contributor to the premature mortality gap. These findings call for routine screening, identification and treatment, using the Alcohol Use Disorders Identification Test (AUDIT-C) in both primary and secondary care to detect alcohol consumption and misuse among people diagnosed with psoriasis.

Psoriasis is a common immune-mediated skin disease producing significant morbidity. Tumour necrosis factor (TNF)-alpha, a pro-inflammatory cytokine, plays a key role in the cutaneous inflammation characteristic of psoriasis. Infliximab is a chimeric monoclonal antibody that specifically binds to TNF-alpha, thereby blocking its biological activity. Data from Phase II and III studies indicate that infliximab is a highly effective, rapidly acting systemic therapy for patients with moderate-to-severe psoriasis. Regular 8-weekly infusions of infliximab maintain significant clinical improvement in the majority of patients for at least 1 year. Infliximab is generally well tolerated, but patients may be susceptible to infection and malignancy.

PKC isoforms tau, alpha, and beta play fundamental roles in the activation of T cells and other immune cell functions. Here we show that the PKC inhibitor AEB071 both abolishes the production of several cytokines by activated human T cells, keratinocytes, and macrophages in vitro and inhibits an acute allergic contact dermatitis response in rats. To translate these findings into humans, single and multiple ascending oral doses of AEB071 were administered to healthy volunteers and patients with psoriasis, respectively. AEB071 was well tolerated with no clinically relevant laboratory abnormalities. Ex vivo stimulation of lymphocytes from subjects exposed to single doses of AEB071 resulted in a dose-dependent inhibition of both lymphocyte proliferation and IL2 mRNA expression. Clinical severity of psoriasis was reduced up to 69% compared with baseline after 2 weeks of treatment, as measured by the Psoriasis Area Severity Index (PASI) score. The improvement in psoriasis patients was accompanied by histological improvement of skin lesions and may be partially explained by a substantial reduction of p40+ dermal cells, which are known to mediate psoriasis. These data suggest that AEB071 could be an effective novel treatment regimen for psoriasis and other autoimmune diseases, and that AEB071 warrants long-term studies to establish safety and efficacy.

An association between systemic malignancy and cutaneous manifestations has long been recognized. The cutaneous features that can occur are numerous and heterogeneous, and many different etiologic mechanisms are represented - from direct tumor invasion of skin or distant metastases to a wide variety of inflammatory dermatoses that may occur as paraneoplastic phenomena. In addition, there are a number of inherited syndromes that carry an increased risk of cutaneous as well as internal malignancies. While some of these inherited syndromes and paraneoplastic phenomena are exceedingly rare, all clinicians will be aware of the common cutaneous manifestations of advanced malignant disease such as generalized xerosis and pruritus. This review classifies these wide-ranging cutaneous manifestations of internal malignancy into five basic groups and provides practical advice regarding diagnosis and screening of patients who initially present with a cutaneous complaint. Also included is up-to-date information on two rapidly expanding and exciting areas of research that are likely to have far-reaching clinical implications: (i) clarification of underlying humoral mechanisms, for example, in the malignant carcinoid syndrome; and (ii) identification of an increasing number of specific genetic defects that confer a susceptibility to malignancy.Increased clinician awareness regarding the associations between these lesions and internal malignancy or inherited syndromes will facilitate screening and early diagnosis.

Psychological stress is believed to exacerbate inflammatory skin disease but the underlying mechanisms are poorly understood. We investigated the impact of acute social stress--Trier public speaking test--on: epidermal Langerhans' cell (LC) frequency; and cutaneous nerve fiber expression of protein gene product (PGP) 9.5 and calcitonin gene-related peptide (CGRP). Thirty-six healthy volunteers each had a pair of baseline 6 mm biopsies taken from sun-protected buttock skin. A second pair of biopsies was taken from contralateral buttock 4 hours (n=5) or 24 hours (n=15) after the Trier stressor. Controls (n=16) did not perform the Trier and had biopsies 24 hours apart. One of each pair of biopsies (baseline; 4 or 24 hours) was processed for counts of epidermal CD1a(+) LC; the other examined for PGP 9.5 and CGRP expression. We observed a significant (P

The identification of robust endotypes—disease subgroups of clinical relevance—is fundamental to stratified medicine. We hypothesized that HLA-C∗06:02 status, the major genetic determinant of psoriasis, defines a psoriasis endotype of clinical relevance. Using two United Kingdom–based cross-sectional datasets—an observational severe-psoriasis study (Biomarkers of Systemic Treatment Outcomes in Psoriasis; n = 3,767) and a large population-based bioresource (UK Biobank, including n = 5,519 individuals with psoriasis)—we compared demographic, environmental, and clinical variables of interest in HLA-C∗06:02–positive (one or two copies of the HLA-C∗06:02 allele) with those in HLA-C∗06:02‒negative (no copies) individuals of European ancestry. We used multivariable regression analyses to account for mediation effects established a priori. We confirm previous observations that HLA-C∗06:02–positive status is associated with earlier age of psoriasis onset and extend findings to reveal an association with disease expressivity in females (Biomarkers of Systemic Treatment Outcomes in Psoriasis: P = 2.7 × 10 –14, UK Biobank: P = 1.0 × 10 –8). We also show HLA-C∗06:02–negative status to be associated with characteristic clinical features (large plaque disease, OR for HLA-C∗06:02 = 0.73, P = 7.4 × 10 –4; nail involvement, OR = 0.70, P = 2.4 × 10 –6); higher central adiposity (Biomarkers of Systemic Treatment Outcomes in Psoriasis: waist circumference difference of 2.0 cm, P = 8.4 × 10 –4; UK Biobank: waist circumference difference of 1.4 cm, P = 1.5 × 10 –4), especially in women; and a higher prevalence of other cardiometabolic comorbidities. These findings extend the clinical phenotype delineated by HLA-C∗06:02 and highlight its potential as an important biomarker to consider in future multimarker stratified medicine approaches.