Search

Background Sufficient data on access to systemic treatment for patients with psoriasis living in Latin America (LA) including Brazil and Chile are lacking. Understanding the availability and limiting factors of access to treatments can help to improve patient care and decrease long-term healthcare costs. Objectives In association with the Global Psoriasis Atlas, this cross-sectional survey study analysed the availability and insurance reimbursement of systemic treatments for adult patients with psoriasis in Brazil and Chile. Methods A multicentre, cross-sectional Global Healthcare Study on Psoriasis was performed in Brazil and Chile in 2020. For each eligible adult patient with psoriasis, doctors and nurses completed a 48-item questionnaire about clinical aspects of psoriasis including the Psoriasis Area Severity Index (PASI), body surface area (BSA) score and the Dermatology Life Quality Index (DLQI), as well as the availability of systemic treatments and insurance reimbursement status. Between-country differences were compared with Wilcoxon rank sum tests for continuous variables, and a χ2-test or Fisher’s exact test, where appropriate, for categorical variables. The median and interquartile range (IQR) was calculated for non-normal distributed data. Results A total of 1424 patients with psoriasis from 43 centres [27 centres in Brazil (n = 826) and 16 in Chile (n = 598)], were included with a mean (SD) age of 49.1 (16.3) and 49.2 (15.1) years, respectively. Unstratified analyses revealed that patients with psoriasis in Chile had more severe disease than those in Brazil [PASI 11.6 vs. 8.4 (P < 0.001) and BSA 14.7 vs. 12.0 (P = 0.003), respectively]. For patients with moderate-to-severe psoriasis, defined as PASI and/or BSA ≥ 10, systemic nonbiologic drugs were available (81.2% in Brazil and 65.3% in Chile, P ≤ 0.001), but only 37.0% of patients in Brazil and 27.3% in Chile received biologics (P = 0.01). Lack of availability and/or lack of insurance reimbursement for biologic drugs for patients with moderate-to-severe psoriasis was reported for 22.2% (50 of 225) in Brazil and 67.9% (148 of 218) in Chile (P < 0.001). Patients with no access to biologic therapies due to lack of availability/insurance reimbursement had a median PASI of 9.15 (IQR 3.00–14.25) in Brazil and 12.0 (IQR 5.00–19.00) in Chile (P = 0.007), as well as a median BSA of 7.0 (IQR 3.00–15.00) and 12.0 (IQR 5.00–22.50) (P = 0.002), and median DLQI of 11.0 (6.00–15.00) and 21.0 (6.50–25.00) (P = 0.007), respectively. Conclusions Chilean patients had significantly more severe psoriasis compared with Brazilian patients in our study. While nonbiologic treatments for moderate-to-severe psoriasis were available in both LA countries, there is a high need for improvement in access to more effective psoriasis treatments including biologics. Our results highlight a significant gap between treatment recommendations in international psoriasis guidelines and real-world situations in Brazil and Chile.

Background Biologic and nonbiologic immunomodulators, used to treat immune-mediated inflammatory diseases (IMIDs), could impair the immune response to COVID-19 vaccines and thus vaccine effectiveness. Objectives Our objective was to investigate the association between biologic and nonbiologic immunomodulators and seroconversion following the first and second dose of COVID-19 vaccines in patients with IMIDs. Methods Serum samples were collected following the first or second dose of the BNT162b2 or AZD1222 vaccines from patients receiving biologic and/or nonbiologic immunomodulators for one or more of psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease or systemic lupus erythematosus. Seroconversion was defined as a positive Roche Elecsys® Anti-SARS-CoV-2 S (spike protein subunit S1/receptor binding domain) immunoassay (≥ 0.8 U mL–1). Association between immunomodulator exposure and seroconversion was assessed using logistic regression, adjusting for age and sex. Results After excluding those with prior COVID-19, post-first vaccine dose samples from 193 participants and post-second dose samples from 312 participants were included in the analysis. Following the first vaccine dose, 17.6% (n = 34) of participants did not seroconvert. Seroconversion was reduced for those on nonbiologic [adjusted odds ratio (OR) 0.29, 95% confidence interval (CI) 0.12–0.69] or combined nonbiologic and biologic treatment (adjusted OR 0.14, 95% CI 0.045–0.45) compared with those on biologic monotherapy. Subgroup analysis demonstrated reduced odds of seroconversion in those on methotrexate (adjusted OR 0.097, 95% CI 0.19–0.49) or prednisolone treatment (adjusted OR 0.044, 95% CI 0.002–1.00) relative to tumour necrosis factor-α inhibitor monotherapy. No participants receiving rituximab (n < 5) seroconverted after the first vaccine dose. Following the second vaccine dose, 1.6% of all participants did not seroconvert. Non-seroconversion was associated with receiving rituximab (n = 3 of 4) compared with those receiving other therapies (n = 2 of 308, P < 0.001). Post hoc analyses demonstrated that non-seroconversion was associated with age [adjusted OR 0.18, 95% CI 0.037–0.93 for those aged 60 years and over (reference category age 18–39 years)], but not sex, ethnicity or vaccine type. Conclusions Treatment with nonbiologics, particularly methotrexate, is associated with impaired seroconversion following two BNT162b2 or AZD1222 vaccine doses, in patients with IMIDs. These findings are consistent with those of other published studies. While this could indicate reduced protection against COVID-19, the immunological parameters that correlate most closely with vaccine effectiveness need to be defined to reach this conclusion.

Generalized pustular psoriasis (GPP) is a rare auto-inflammatory skin disease characterised by acute episodes of sterile pustule formation. Diagnosis and treatment of the disease have historically been complicated by a lack of awareness, and no consistent global definition or clinical coding standards. Now acknowledged as a distinct clinical entity with a recognised genetic component, GPP can take a serious and life-threatening course due to systemic inflammatory complications and its association with various comorbidities. As with other rare diseases, there are significant challenges to understanding the epidemiology of GPP, notably a small patient population, non-standardised study methodologies and ethnic differences in its presentation. A clearer understanding of GPP is therefore required for clinicians to better manage patients with this rare condition. In this review article, we present an overview of the available data on GPP prevalence estimates in key demographics and report the frequency of genetic mutations associated with the disease. We detail the incidence of known comorbidities and summarise the data on mortality and assigned causes of death. Lastly, we discuss the various factors that impact the collection, interpretation and comparison of these data.

Although retinol skin care products improve the appearance of photoaged skin, there is a need for an effective retinol concentration that provides skin benefits without irritation.To compare the efficacy of topical 0.1%, 0.3% and 1% retinol in remodelling the cutaneous architecture in an in vivo experimental patch test study, and to determine tolerance of the most effective formulations when used in a daily in-use escalation study.For the patch test study, retinol products were applied under occlusion, to the extensor forearm of photoaged volunteers (n = 5; age range 66-84 years), and 3 mm skin biopsies obtained after 12 days. Effects of different retinol concentrations, and a vehicle control, on key epidermal and dermal biomarkers of cellular proliferation and dermal remodelling were compared to untreated baseline. Separately, participants (n = 218) recorded their tolerance to 0.3% or 1% retinol over a six-week, approved regimen, which gradually increased the facial applications to once nightly.Retinol treatment induced a stepwise increase in epidermal thickness and induced the expression of stratum corneum proteins, filaggrin and KPRP. 0.3% retinol and 1% retinol were comparably effective at inducing keratinocyte proliferation in the epidermis, whilst reducing e-cadherin expression. Fibrillin-rich microfibril deposition was increased following treatment with 0.3% and 1% retinol (p 0.01); other dermal components remained unaltered (e.g., fibronectin, collagen fibrils, elastin), and no evidence of local inflammation was detected. The in-use study found that 0.3% retinol was better tolerated than 1% retinol, with fewer and milder adverse events reported (χThis study suggests that 1% and 0.3% retinol concentrations were similarly effective at remodelling photodamaged skin in an in vivo model of long-term use. Use of 0.3% retinol in the escalation study was associated with fewer adverse reactions when applied daily. Hence, 0.3% retinol may be better tolerated than 1% retinol, thereby allowing longer-term topical application.Même si les produits de soins pour la peau à base de rétinol améliorent l'apparence de la peau photovieillie, il est nécessaire d'obtenir une concentration efficace de rétinol procurant des bénéfices cutanés sans irritation.Comparer l'efficacité du rétinol à 0.1%, 0.3% et 1% en application locale dans le remodelage de l'architecture cutanée dans une étude d'irritation cutanée in vivo expérimental, et déterminer la tolérance des formulations les plus efficaces lorsqu'elles sont utilisées dans une étude à doses progressives quotidiennes en cours d'utilisation. MÉTHODES: Pour l'étude d'irritation cutanée, des produits à base de rétinol ont été appliqués sous occlusion, sur le muscle extenseur de l'avant-bras de volontaires présentant des signes de photovieillissement (n = 5; tranche d'âge: 66 à 84 ans), et des biopsies cutanées de 3 mm ont été obtenues après 12 jours. Les effets des différentes concentrations de rétinol, et d'un véhicule témoin sur les principaux biomarqueurs épidermiques et dermiques de la prolifération cellulaire et du remodelage dermique ont été comparés à ceux observés à une région non traitée. Séparément, les participants (n = 218) ont enregistré leur tolérance au rétinol à 0.3% ou 1% au cours d'un schéma posologique approuvé de six semaines, qui a progressivement augmenté les applications faciales à une fois par nuit. RÉSULTATS: Le traitement par rétinol a induit une augmentation progressive de l'épaisseur épidermique, et a induit l'expression des protéines de la couche cornée, la filaggrine et le KPRP. Le rétinol à 0.3% et le rétinol à 1% étaient aussi efficaces pour induire la prolifération des kératinocytes dans l'épiderme, tout en réduisant l'expression de la cadhérine E. Le dépôt de microfibrilles riches en fibrilline a augmenté après un traitement par rétinol à 0.3% et 1% (p 0.001).Cette étude suggère que les concentrations de rétinol de 1% et 0.3% étaient aussi efficaces pour remodeler la peau photolésée dans un modèle in vivo lors d'une utilisation à long terme. L'utilisation de rétinol à 0.3% dans l'étude à doses progressives a été associée à moins d'effets indésirables lorsqu'il est appliqué quotidiennement. Par conséquent, le rétinol à 0.3% peut être mieux toléré que le rétinol à 1%, permettant ainsi une application topique à plus long terme.

Previous studies have discussed the low prevalence of psoriasis among Indigenous peoples of South America. The state of Roraima - Brazil, where the present study was performed, is crossed by the Equator line. It is likely that key factors for the absence of psoriasis in this indigenous population are: genetic; lack of environmental triggers; and high sun exposure.

Background Generalised pustular psoriasis (GPP) is a systemic inflammatory disease that can be severe, debilitating, and life-threatening. Uncontrolled activation of interleukin-36 (IL-36) pro-inflammatory activity may underlie the pathogenesis of GPP. Currently, GPP-specific treatment options are limited. Objectives To evaluate the efficacy and safety of the anti-IL-36 receptor antibody imsidolimab in subjects with GPP. Methods In an open-label, single-arm, multiple-dose study, subjects with GPP were treated with imsidolimab to assess clinical efficacy, tolerability, and safety. Subjects received an intravenous (IV) imsidolimab 750 mg dose on Day 1, followed by 3 doses of subcutaneous (SC) imsidolimab 100 mg administered on Days 29, 57, and 85. The primary efficacy endpoint was the proportion of subjects that achieved a clinical response at Week 4 and Week 16 following treatment with imsidolimab as measured by the Clinical Global Impression (CGI) scale. Results A total of 8 patients were enrolled and 6 subjects completed the study. Responses were observed as early as Day 3, most rapidly for pustulation relative to other manifestations of GPP, with continued and consistent improvement across multiple efficacy assessments at Day 8, Day 29, and through Day 113. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. No subject discontinued the study due to a non-serious TEAE. Two subjects experienced serious adverse events (SAEs) and no deaths were reported. Conclusions Imsidolimab demonstrated a rapid and sustained resolution of symptoms and pustular eruptions in subjects with GPP. It was generally well-tolerated, associated with acceptable safety, and is advancing to Phase 3 trials. These data support targeting of IL-36 signalling with a specific antibody, imsidolimab, as a therapeutic option for this severely debilitating condition. The study was registered under EudraCT Number 2017-004021-33 and NCT 03619902.

Background Tumour necrosis factor-alpha inhibitors (TNFi) have revolutionized the treatment of moderate-to-severe psoriasis. Following patent expiry of the originator biologics, TNFi biosimilars became available, presenting the opportunity for significant reductions in drug costs. Objectives To describe the uptake of TNFi biosimilars for psoriasis treatment in the UK and Ireland. Methods This observational cohort study utilizes data from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR), a national pharmacovigilance study register for patients with psoriasis on systemic treatments. We analysed biosimilar uptake trends over time in nine geographical regions of England along with Wales, Scotland, Northern Ireland and the Republic of Ireland. We assessed the incidence of switching to biosimilars in an originator-user cohort (switchers). Patients on originators infliximab, etanercept and adalimumab at the time originator patents expired, entered the cohort on 1 February 2015, August 2015 and October 2018, respectively, and were followed up until 31 October 2021. Trends in biosimilar initiations were assessed in an adalimumab-naïve cohort who started adalimumab between 1 October 2018 and 31 July 2019 (starters). We assessed the associations between patient factors and originator-to-biosimilar switching and biosimilar initiation using a multivariable Cox regression model and a multivariable logistic regression model, respectively. Results Included in the originator-user cohort were 4202 patients (209 on infliximab, 742 on etanercept and 3251 on adalimumab). For infliximab, etanercept and adalimumab, respectively, the cumulative incidence of originator-to-biosimilar switching increased with time to 14.8%, 23.6% and 66.6% after 3 years. Across geographical regions, 3-year switching rates varied from 0% to 43.7% for infliximab; from 0% to 40.4% for etanercept; and from 12.5% to 84.3% for adalimumab. Out of the 528 patients included in the adalimumab-naïve cohort, 67.8% started on biosimilars. Originator-to-biosimilar switching and biosimilar initiation were more common in men and in patients who had lower Psoriasis Area and Severity Index at cohort entry. Conclusions The uptake of biosimilars increased over time and varied considerably across the UK and Ireland; adalimumab had the highest biosimilar uptake rate compared with that of other TNFi drugs.

Both early clinical improvement and long-term maintenance of clinical efficacy of treatments matter to patients with psoriasis. We compared cumulative clinical benefits of treatment with biologics over 1 year based on the area under the curve (AUC) for Psoriasis Area and Severity Index (PASI) 100 and PASI 90 responses in patients with moderate-to-severe psoriasis using a network meta-analysis (NMA).Published phase 3 randomized, placebo- or active-controlled clinical trial data for biologics approved for the treatment of moderate-to-severe psoriasis were obtained from a systematic literature review up to 30 September 2020. Eighteen clinical trials that included data from baseline to 48 or 52 weeks where AUC could be calculated were included. Data were compared using a fixed-effect model with a separate random-effect baseline model to account for effects of the placebo arm. Cumulative clinical benefit was estimated using the AUC for PASI 100 and PASI 90 responses (complete and almost-complete skin clearance, respectively). Normalized AUC was compared using Bayesian NMA. Cumulative days of response were calculated using normalized AUC and study duration.Interleukin (IL)-17 and IL-23 inhibitors demonstrated greater cumulative clinical benefits for both PASI 100 and PASI 90 versus IL-12/23 and tumor necrosis factor inhibitors. Over 52 weeks, cumulative days with PASI 100 were greatest with ixekizumab [158.7 (95% credible interval, 147.4, 170.0) days] followed by risankizumab [154.0 (144.9, 163.4) days]; PASI 90 days were greatest with risankizumab [249.3 (239.5, 259.2) days] followed by ixekizumab [238.8 (227.1, 250.8) days]. Both ixekizumab and risankizumab showed greater cumulative days with PASI 100 or PASI 90 responses versus secukinumab [117.9 (110.7, 125.2) and 215.5 (208.2, 223.1) days, respectively] and greater cumulative days with PASI 100 versus guselkumab [130.7 (120.5, 140.9) days].For complete and almost-complete skin clearance, ixekizumab and risankizumab provided the greatest cumulative clinical benefits over 1 year.

ObjectivesTo investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).MethodsDemographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression.ResultsOf 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25–2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39–2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42–0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19.ConclusionOlder age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

ObjectivePatients with psoriasis have an increased prevalence of type 2 diabetes when compared to the general population. Research suggests that type 2 diabetes (T2D) as well as obesity may have an impact on patients' response to treatment. This post-hoc analysis reports the efficacy of ixekizumab in treating moderate-to-severe psoriasis in patients with prediabetes or T2D.Method and materialsUNCOVER-1, UNCOVER-2, and UNCOVER-3 were three Phase 3, multicenter, randomized, double-blind, placebo-controlled trials that evaluated the efficacy and safety of ixekizumab in adult patients with moderate-to-severe psoriasis. Patients were aged ≥18 years with chronic moderate-to-severe psoriasis (defined as ≥10% body surface area affected, static Physician Global Assessment ≥3, and Psoriasis Area and Severity Index [PASI] ≥12 at screening and baseline) who were candidates for phototherapy or systemic therapy. UNCOVER-1, UNCOVER-2, and UNCOVER-3 participants received ixekizumab as per label (that is, an initial dose of two subcutaneous injections [160 mg in total] at Week 0, followed by 80 mg every 2 weeks through Week 12 and 80 mg every 4 weeks thereafter through Week 60).ResultsThe proportions of patients with prediabetes, T2D and normoglycemia that achieved PASI75, PASI90, and PASI100 at Week 60 were similar. Results suggest that patients with T2D were slower to achieve PASI100 than patients with prediabetes or those with normoglycemia. Ixekizumab had no effect on any metabolic markers in patients receiving the treatment.ConclusionsDespite the higher rate of obesity and extreme obesity in patients with prediabetes and T2D, ixekizumab was an efficacious treatment in treating patients with psoriasis.

The menopause can lead to epidermal changes that are alleviated by hormone replacement therapy (HRT). We hypothesise that these changes could relate to altered ceramide production, and that oestrogen may have a role in keratinocyte ceramide metabolism. White Caucasian women were recruited into three groups: pre-menopausal (n = 7), post-menopausal (n = 11) and post-menopausal taking HRT (n = 10). Blood samples were assessed for hormone levels, transepidermal water loss was measured to assess skin barrier function, and stratum corneum lipids were sampled from photoprotected buttock skin. Ceramides and sphingomyelins were analysed by ultraperformance liquid chromatography with electrospray ionisation and tandem mass spectrometry. Post-menopausal stratum corneum contained lower levels of ceramides, with shorter average length; changes that were not evident in the HRT group. Serum oestradiol correlated with ceramide abundance and length. Ceramides had shorter sphingoid bases, indicating altered de novo ceramide biosynthesis. Additionally, post-menopausal women had higher sphingomyelin levels, suggesting a possible effect on the hydrolysis pathway. Treatment of primary human keratinocytes with oestradiol (10 nM) increased production of CER[NS] and CER[NDS] ceramides, confirming an effect of oestrogen on cutaneous ceramide metabolism. Taken together, these data show perturbed stratum corneum lipids post-menopause, and a role for oestrogen in ceramide production.

Psoriasis is a common, chronic papulosquamous skin disease occurring worldwide, presenting at any age, and leading to a substantial burden for individuals and society. It is associated with several important medical conditions, including depression, psoriatic arthritis, and cardiometabolic syndrome. Its most common form, chronic plaque or psoriasis vulgaris, is a consequence of genetic susceptibility, particularly in the presence of the HLA-C*06:02 risk allele, and of environmental triggers such as streptococcal infection, stress, smoking, obesity, and alcohol consumption. There are several phenotypes and research has separated pustular from chronic plaque forms. Immunological and genetic studies have identified IL-17 and IL-23 as key drivers of psoriasis pathogenesis. Immune targeting of these cytokines and of TNFα by biological therapies has revolutionised the care of severe chronic plaque disease. Psoriasis cannot currently be cured, but management should aim to minimise physical and psychological harm by treating patients early in the disease process, identifying and preventing associated multimorbidity, instilling lifestyle modifications, and employing a personalised approach to treatment.

Background Psoriasis is a chronic inflammatory skin disease associated with several important medical comorbidities. There are scant data available on the comorbidities of patients with psoriasis in South America. Aim To examine the comorbidity profile of adult patients with psoriasis in Chile and its association with severity of psoriasis. Methods This was a multicentre, cross-sectional study involving 16 hospitals and clinics in Chile, which used a 48-item questionnaire to study clinician- and patient-reported outcomes and comorbidities. Inferential analyses were performed by psoriasis severity, using Fisher exact test, Student t-test and multivariable logistic regression. Results In total, 598 adult patients with psoriasis were included (51.1% male; mean age 49.2 ± 15.1 years); 48.5% mild and 51.4% moderate to severe; Psoriasis Area and Severity Index 11.6 ± 11.5; body surface area 14.7 ± 18.2%. Plaque psoriasis was the most common phenotype (90.2%), followed by guttate (13.4%). Psoriatic arthritis occurred in 27.3% of patients. Comorbidities were reported in 60.2% of all patients with psoriasis. Frequent concomitant diseases were obesity (25.3%), hypertension (24.3%), Type 2 diabetes mellitus (T2DM) (18.7%), dyslipidaemia (17.4%), metabolic syndrome (16.7%) and depression (14.4%). After adjustment, significant associations were found between moderate to severe psoriasis and obesity, T2DM and nonalcoholic fatty liver disease (NAFLD) compared with mild psoriasis. Conclusions We report a large study of comorbidities, including depression, dyslipidaemia, T2DM and NAFLD, in people with psoriasis in Chile. The prevalence of comorbidities with psoriasis in Chile appears similar to that found in Western countries, and emphasizes the importance of assessing patients with psoriasis for risk factors for and presence of, comorbid disease in a multidisciplinary setting.

Summary Background There are no population-based epidemiological data on psoriasis in Southeast Asia, including Malaysia. Objectives To determine the incidence and prevalence of psoriasis over 11 years in multiethnic Johor Bahru, Malaysia. Methods A population-based cohort study was made using the Teleprimary Care database between January 2010 and December 2020. Cases of psoriasis, identified by ICD-10 diagnostic codes, were validated by dermatologists. Annual prevalence and incidence were estimated and stratified by age, sex and ethnicity. Results We identified 3932 people with dermatologist-confirmed psoriasis, including 1830 incident cases, among 1 164 724 Malaysians, yielding an 11-year prevalence of 0·34% [95% confidence interval (CI) 0·33–0·35] and incidence of 34·2 per 100 000 person-years (95% CI 32·6–35·8). Rates were higher in Indian patients; the prevalences were 0·54% (0·50–0·58) in Indian, 0·38% (0·36–0·40) in Chinese and 0·29% (0·28–0·30) in Malay patients, and the respective incidences per 100 000 person-years were 52·5 (47·3–57·7), 38·0 (34·1–41·8) and 30·0 (28·2–31·8). Rates were higher in males; the prevalence was 0·39% (0·37–0·41) in males and 0·29% (0·27–0·30) in females, and the respective incidences per 100 000 person-years were 40·7 (38·2–43·2) and 28·3 (26·4–30·3). Between 2010 and 2020, annual psoriasis prevalence and incidence increased steadily from 0·27% to 0·51% and from 27·8 to 60·9 per 100 000 person-years, respectively. Annual rates were consistently higher in male and Indian patients. Overall, psoriasis was significantly more common in males than females [odds ratio (OR) 1·37, 95% CI 1·29–1·46] and in Indian and Chinese patients vs. Malay (OR 1·85, 1·71–2·01 and OR 1·30, 1·20–1·41, respectively). Prevalence increased with age, with the highest rates in the groups aged 50–59 and 60–69 years at 0·67% and 0·66%, respectively. A modest bimodal trend in age of psoriasis onset was observed, with first and second peaks at 20–29 and 50–59 years. Disease onset was significantly earlier in females than males [mean (SD) 36·8 (17·3) vs. 42·0 (17·2) years, P < 0·001] and in Malay vs. Indian and Chinese patients [mean (SD): Malay 36·4 (17·5), Indian 40·8 (15·2), Chinese 47·4 (16·9) years, P < 0·001]. Conclusions We found that psoriasis incidence and prevalence are increasing and varied by age, sex and ethnicity. Our findings should help inform healthcare planning and management for patients with psoriasis in Malaysia. What is already known about this topic? The incidence and prevalence of psoriasis are generally lower in Asian populations and children.There is a lack of agreement on sex-specific differences in psoriasis incidence and prevalence.There has been no population-based study on the incidence and prevalence of psoriasis in Southeast Asia, including Malaysia.There is no information on differences in psoriasis prevalence and incidence by sex, age and ethnicity in Malaysia. What does this study add? Psoriasis incidence and prevalence are increasing in the multiethnic population of Johor Bahru, Malaysia.Incidence and prevalence rates were higher in male than female patients and were consistently highest among Indian patients, followed by Chinese and Malay.A modest bimodality in the age of psoriasis onset was observed among the groups aged 20–29 and 50–59 years.Psoriasis onset was significantly later in male than female patients and in Chinese vs. Indian and Malay patients.

The skin immune system is tightly regulated to prevent inappropriate inflammation in response to harmless environmental substances. This regulation is actively maintained by mechanisms including cytokines and cell surface receptors and its loss results in inflammatory disease. In the case of psoriasis, inappropriate immune activation leads to IL-17-driven chronic inflammation, but molecular mechanisms underlying this loss of regulation are not well understood. Immunoglobulin family member CD200 and its receptor, CD200R1, are important regulators of inflammation. Therefore, we determined if this pathway is dysregulated in psoriasis, and how this affects immune cell activity.Human skin biopsies were examined by quantitative polymerase chain reaction, flow cytometry, and immunohistochemistry. The role of CD200R1 in regulating psoriasis-like skin inflammation was examined using CD200R1 blocking antibodies in mouse psoriasis models. CD200R1 blocking antibodies were also used in an in vivo neutrophil recruitment assay and in vitro assays to examine macrophage, innate lymphoid cell, γδ T cell, and neutrophil activity.We reveal that CD200 and signaling via CD200R1 are reduced in non-lesional psoriasis skin. In mouse models of psoriasis CD200R1 was shown to limit psoriasis-like inflammation by enhancing acanthosis, CCL20 production and neutrophil recruitment, but surprisingly, macrophage function and IL-17 production were not affected, and neutrophil reactive oxygen species production was reduced.Collectively, these data show that CD200R1 affects neutrophil function and limits inflammatory responses in healthy skin by restricting neutrophil recruitment. However, the CD200 pathway is reduced in psoriasis, resulting in a loss of immune control, and increased neutrophil recruitment in mouse models. In conclusion, we highlight CD200R1:CD200 as a pathway that might be targeted to dampen inflammation in patients with psoriasis.

We report a comprehensive summary of the safety outcomes in adult patients with moderate-to-severe psoriasis with up to 5 years of exposure to ixekizumab.Long-term safety of the IL-17A antagonist ixekizumab was assessed from 17 randomized trials. Treatment-emergent adverse events (TEAEs)-adjusted incidence rates (IRs) per 100 patient-years (PY) within 1-year time periods through 19 March 2021 were calculated for all patients treated with at least one dose of ixekizumab. Reported cases of major adverse cerebro-cardiovascular events (MACE) and inflammatory bowel disease (IBD) were adjudicated.A total of 6892 adult patients with a cumulative exposure of 18,025.7 PY were included. The IRs per 100 PY for any TEAE and serious adverse events (AEs) were 32.5 and 5.4. IR of discontinuation because of AE was 2.9. A total of 36 deaths were reported. IR of serious infections was low (1.3). There were no confirmed cases of reactivation of tuberculosis (TB). IR of Candida infections (IR 1.9) was low; most cases of Candida were localized, and no systemic cases were reported. IRs of injection site reactions and allergic/hypersensitivity were 5.9 and 5.6, respectively. No confirmed cases of anaphylaxis were observed. IRs were low for malignancies, depression, cytopenia, and MACE (all ≤ 1.2). IBD events were uncommon, although a total of 31 patients (IR 0.2) had confirmed IBD (ulcerative colitis, n = 18; Crohn disease, n = 13). Across safety topics, IRs decreased or remained constant over time.The long-term safety profile for ixekizumab is consistent with that previously reported in patients with psoriasis. No new or unexpected safety events were detected.

IntroductionAgeing is accompanied by an age-related decrease in mobility or cognitive and sensory functions; in addition, physiological changes in the skin occur with age. Therefore, the skin requires appropriate care and observation in order to prevent or manage a variety of dermatological diseases and conditions, and to prevent or minimise effects on the quality of life.Globally, most older people live at home, and the need to establish sustainable structures and processes to support and to care for people at home for as long as possible has been emphasised. The body of evidence supporting screening, diagnosis and management of skin conditions in older people living at home has not been collated and summarised to date. The aim of this scoping review is to describe and summarise the extent and nature of the available body of evidence in this regard.Methods and analysisThis scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Eligibility criteria were developed using the Population, Concept and Context framework, and the search will focus on systematic and scoping reviews as well as clinical practice guidelines. Two reviewers will conduct systematic searches, screen and select identified evidence as well as extract and chart data, independently. Finally, data will be systematically analysed and summarised descriptively to map existing evidence and identify gaps.Ethics and disseminationDue to the nature of research, not involving humans or unpublished secondary data, approval of an ethics committee is not required. The dissemination of findings is planned via professional networks and publication in scientific open access journals.

The skin is exposed to environmental challenges and contains skin-resident immune cells, including mast cells (MCs) and CD8 T cells that act as sentinels for pathogens and environmental antigens. Human skin MCs and their mediators participate in the maintenance of tissue homeostasis and regulate the recruitment and activity of immune cells involved in the pathogenesis of skin diseases. The cutaneous CD8 T cell compartment is comprised of long-persisting resident memory T cells (TRM) and migratory or recirculating cells; both populations provide durable site immune surveillance. Several lines of evidence indicate that MC-derived products, such as CCL5 and TNF-α, modulate the migration and function of CD8 T cells. Conversely, activated CD8 T cells induce the upregulation of MC costimulatory molecules. Moreover, the close apposition of MCs and CD8 T cells has been recently identified in the skin of several dermatoses, such as alopecia areata. This review outlines the current knowledge about bidirectional interactions between human MCs and CD8 T cells, analyses the alteration of their communication in the context of three common skin disorders in which these cells have been found altered in number or function—psoriasis, atopic dermatitis, and vitiligo—and discusses the current unanswered questions.

Palmoplantar pustulosis (PPP) is a severe inflammatory skin disorder characterized by eruptions of painful, neutrophil-filled pustules on the palms and soles. Although PPP has a profound effect on quality of life, it remains poorly understood and notoriously difficult to treat.We sought to investigate the immune pathways that underlie the pathogenesis of PPP.We applied bulk and single-cell RNA sequencing (RNA-Seq) methods to the analysis of skin biopsy samples and peripheral blood mononuclear cells. We validated our results by flow cytometry and immune fluorescence microscopy RESULTS: Bulk RNA-Seq of patient skin detected an unexpected signature of T-cell activation, with a significant overexpression of several TPPP is associated with complex T-cell activation patterns and may explain why biologic drugs that target individual T helper cell populations have shown limited therapeutic efficacy.

Fibrillin-rich microfibrils (FRMs) constitute integral components of the dermal elastic fibre network with a distinctive ultrastructural 'beads-on-a-string' appearance that can be visualised using atomic force microscopy and characterised by measurement of their length and inter-bead periodicity. Their deposition within the dermis in photoprotected skin appears to be contingent on skin ethnicity, and influences the ultrastructure of papillary - but not reticular - dermal FRMs. Truncation and depletion of FRMs at the dermal-epidermal junction of skin occurs early in photoageing in people with lightly pigmented skin; a process of accelerated skin ageing that arises due to chronic sun exposure. Accumulation of ultraviolet radiation (UVR)-induced damage, either by the action of enzymes, oxidation or direct photon absorption, results in FRM remodelling and changes to ultrastructure. In the current study, the direct effect of UVR exposure on FRM ultrastructure was assayed by isolating FRMs from the papillary and reticular dermis of photoprotected buttock skin of individuals of either black African or white Northern European ancestry and exposing them to solar-simulated radiation (SSR). Exposure to SSR resulted in significant reduction in inter-bead periodicity for reticular dermis-derived FRMs across both cohorts. In contrast, papillary dermal FRMs exhibited significantly increased inter-bead periodicity, with the magnitude of damage greater for African FRMs, as compared to Northern European FRMs. Our data suggest that FRMs of the dermis should be considered as two distinct populations that differentially accrue damage in response to SSR. Furthermore, papillary dermal FRMs derived from black African subjects show greater change following UVR challenge, when extracted from skin. Future studies should focus on understanding the consequences of UVR exposure in vivo, regardless of skin ethnicity, on the molecular composition of FRMs and how this UVR-induced remodelling may affect the role FRMs play in skin homeostasis.

Stratified medicine is the tailoring of treatment to the individual characteristics of each patient. This is a challenging task in the context of psoriasis, a complex disease with a variety of phenotypic presentations and a comorbidity burden that extends beyond cutaneous manifestations. In recent years, considerable progress has been made in understanding the immunology of psoriasis, and this has informed the development of increasingly precise and efficacious therapies. However, not all patients respond to biologic therapy, and access is limited to patients with moderate to severe disease. However, subpopulations of patients are emerging with distinct patterns of response to therapy, largely determined by clinical and pharmacogenomic factors. Despite progress to date, the natural history of psoriasis remains poorly understood. It is likely that disease onset, progression, development of comorbidities and response to therapy are due to a combination of genetic, inflammatory and environmental factors. We envision that a greater understanding of the natural history of psoriasis will be a key factor in progressing a stratified medicine approach to patient care, as will earlier intervention in the course of the disease.

Due to the chronic nature of psoriasis, it is important to assess the sustained response of treatments over time.To assess the efficacy of continuous treatment with guselkumab (an interleukin-23 blocker) through two years in the phase 3 VOYAGE 1 trial.Patients were randomized to placebo, guselkumab, or adalimumab at baseline. Placebo-randomized patients crossed over to guselkumab at week 16 (placebo→guselkumab) and adalimumab-randomized patients crossed over to guselkumab at week 52 (adalimumab→guselkumab); all patients received open-label guselkumab beyond week 52. Efficacy was assessed based on the Psoriasis Area and Severity Index (PASI; proportion of patients achieving ≥75%, 90%, or 100% improvement [PASI 75/90/100]) and the Investigator's Global Assessment (IGA; proportion achieving nearly clear [IGA 0/1] or completely clear [IGA 0]). As pre-specified, efficacy data were analyzed using non-responder imputation (NRI; patients with missing data counted as non-responders) after applying treatment failure rules (TFR; patients meeting TFR counted as non-responders thereafter) through week 48 and by applying TFR only from week 52 through 100. All endpoints were also analyzed using NRI and As Observed methodology for the guselkumab group through week 100.The clinical responses were maintained through week 100 based on all three analyses. Based on pre-specified analyses, proportions of patients who achieved PASI 75, PASI 90, PASI 100, IGA 0/1, and IGA 0 were 94.8%, 82.1%, 49.0%, 82.4%, and 53.8%, respectively, at week 100. Results were similar for the placebo→guselkumab and adalimumab→guselkumab groups at week 100. As expected, proportions of patients achieving these endpoints were similar based on As Observed analyses and slightly lower when the more conservative NRI rules were applied.High levels of efficacy were maintained through two years of continuous treatment among guselkumab-treated patients, and efficacy improved through two years among adalimumab-treated patients who crossed over to guselkumab at one year. J Drugs Dermatol. 2018;17(8):826-832.

Oral methotrexate (MTX) has been a first line systemic agent in the treatment of chronic plaque psoriasis (CPP) for more than 50 years. Parenteral MTX, administered as a subcutaneous (SC) injection has gained favour in recent years. The effectiveness of SC MTX has been proven in rheumatological conditions but there has been no assessment of its role in CPP.We retrospectively reviewed case notes of 85 patients prescribed SC MTX for psoriasis in three dermatology centres in the UK (Betsi Cadwaladr University Health Board, Western Infirmary, Glasgow, and Salford Royal NHS Foundation Trust). Audit department approval was sought and granted.A total of 85 patients (44 male; 41 female; age range 14 - 78 years, mean 44 years; 79 Caucasian, 6 Asian) with CPP were identified. The average duration of psoriasis was 19 years [range 3 - 60 years]. Co-morbidities included depression, diabetes mellitus, hypertension, epilepsy, obesity, ischaemic heart disease, and hyperlipidaemia; 29 patients had no associated co-morbidities. Psoriatic arthritis was noted in 18 patients. Previous treatments included phototherapy (both narrow band ultraviolet B [TLO1] and psoralen and ultraviolet A [PUVA])(n=60), oral MTX (n=82), ciclosporin (n=37), acitretin (n=19), fumaric acid esters (n=20), hydroxycarbamide (n=6), mycophenolate mofetil (n=2), and repeated in-patient admissions (n=2). Oral MTX was stopped due to nausea (n=43), ineffectiveness (n=13) or partial response (n=11), headache (n=3), increased liver enzymes (n=2), and lethargy (n=2). The median number of systemic agents used prior to SC MTX was 3 (mean 2.65, range 1 to 6 agents). The weekly dose of SC MTX varied between 7.5mg to 30 mg (mean 18.5mg, median 20mg) and had been used for 2 months to 67 months (mean 14 months; median 9 months). Folic acid supplementation was used in every patient. The patients were reviewed between 6 weeks to 3 months once treatment was fully established. Using a pre-determined "adjective list" (where specific adjectives were used to denote those who responded or did not respond to treatment), patients were classified as "responders" (n=59) or "non-responders" (n=26).This study suggests that SC MTX is an effective option in patients with CPP who have failed oral MTX and could be a worthwhile consideration prior to commencement of a biologic agent. Furthermore, the SC route may be a viable first choice of MTX administration. A randomised controlled trial comparing oral and SC MTX is required to validate these findings.

Systemic sclerosis (SSc)-related digital ulcers (DU) cause significant pain and disability and are often a primary endpoint in clinical trials. However, their pathophysiology has been little studied. The objectives of this prospective study were to determine whether laser Doppler imaging (LDI) and thermography can identify ischaemic components in both fingertip and extensor surface DU and assess ulcer healing.Patients prospectively reported new DU over a year. Patients' DU underwent imaging until the ulcer had healed. Ischaemia was defined as lower blood flow or skin temperature (and inflammation as higher) within the ulcer, compared to a non-affected site.53 ulcers (19 fingertip, 18 extensor, 16 'other' sites) in 17 patients were imaged (53 with LDI, 52 with thermography). For LDI data 32 (60%) ulcers were ischaemic; median perfusion ulcer/unaffected area; 0.79 (range 0.11-2.9). For thermography data 35 (66%) were ischaemic; 0.98 (0.89 to 1.1). Inflammation in the surrounding area was identified for all ulcers by LDI but not thermography. In the 36 ulcers with repeat imaging, LDI showed trends (with healing) towards increased ulcer perfusion (p=0.23) and decreased hyperaemia in adjacent areas (p=0.59). Skin temperature at the ulcer site showed no significant change (p=0.13) but adjacent area showed decreased temperature (p=0.04 signifying decreased blood flow).LDI and thermography are sufficiently sensitive to measure ischaemia in both fingertip and extensor ulcers. LDI was better suited to monitoring change in perfusion with healing (due to higher imaging resolution, or vascular changes occurring in more superficial skin layers).

Up to 40% of patients with rheumatoid arthritis treated with anti-tumour necrosis factor (TNF) drugs do not respond because of primary inefficacy or loss of response. Although one explanation is that immunogenicity leads to the development of anti-drug antibodies and low drug concentrations, the clinical usefulness of pharmacological monitoring is debated. Our aim was to assess whether the presence of anti-drug antibodies and non-trough drug concentrations could predict treatment response in patients with rheumatoid arthritis treated with anti-TNF drugs.331 patients were selected from a multicentre prospective cohort (160 treated with adalimumab, 171 etanercept). Serum samples were collected at 3, 6, and 12 months after treatment initiation. Anti-drug antibodies were measured with RIA, drug concentrations with ELISAs, and Disease Activity Score in 28 joints (DAS28) at each timepoint. Linear and logistic regression, generalised estimating equation (GEE), and receiver operating characteristic curves were used to test the association and predictive value of anti-drug antibodies and non-trough drug concentrations on treatment response (ΔDAS28).835 serial samples were tested (414 adalimumab, 421 etanercept). Anti-adalimumab antibodies were detected in 31 (24·8%) of 125 patients who had completed 12 month follow-up and none of the etanercept patients. The presence of anti-drug antibodies was associated with lower adalimumab concentrations (Spearman r=-0·66, p=0·0041). At 3 months, anti-drug antibody formation and low adalimumab concentrations were significant predictors of poor treatment response at 12 months (area under curve [AUC] 0·68, 95% CI 0·54-0·81, and 0·66, 0·55-0·77, respectively; and both combined 0·71, 0·57-0·85). Adalimumab concentration was the most significant independent predictor of ΔDAS28 after adjustment for confounders (regression coefficient 0·12, 95% CI 0·06-0·18; p=0·003). High etanercept concentrations were associated with better treatment response (p=0·01), but low concentrations at 3 months were not a significant predictor of poor treatment response at 12 months (AUC 0·58, 95% CI 0·46-0·70). In the combined GEE model including adalimumab and etanercept, a body-mass index of 30 kg/m(2) or more was associated with low drug concentrations (regression coefficient 0·78, 95% CI 0·37-1·18; p0·0001).Pharmacological testing in anti-TNF initiated patients is clinically useful even in the absence of trough levels. At 3 months, presence of anti-drug antibodies and low adalimumab concentrations are a significant predictor for poor treatment response at 12 months. Strengths of this study include a large, prospective cohort and use of RIA to measure antibodies (less prone to drug interference). Although non-trough concentrations might have underestimated the frequency of antibodies, their presence still predicted response.MJ is a MRC Clinical Training Fellow supported by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the UK Medical Research Council (grant number G1000417/94909), ICON, GlaxoSmithKline, AstraZeneca, and the Medical Evaluation Unit. Arthritis Research UK (grant ref 20385).

The umbrella term psoriasis is now understood to incorporate several distinct phenotypes or endotypes along the disease spectrum that in turn will dictate different therapies. A stratified medicine approach to psoriasis using this clinical information coupled with pharmacogenomic and immunologic data will become more widely acceptable in the future. Comorbidities associated with psoriasis, such as diabetes, depression, and Crohn disease, and the debate about the interdependence of psoriasis and cardiovascular disease will also dictate future research and holistic and management plans for this complex disease.

Interleukin-22 (IL-22) is a proinflammatory cytokine that has been associated with the pathogenesis of inflammatory skin disorders. However, the impact of IL-22 on microRNA (miRNA) expression in epidermal keratinocytes is unknown. Here we show that IL-22 induces miR-184 in reconstituted human epidermis (RHE) and in the HaCaT keratinocyte cell line. Exposure to IL-22 increased miR-184 expression 8- and 15-fold in RHE and HaCaT cells, respectively. Oncostatin M, an unrelated proinflammatory cytokine, also raised miR-184 expression in RHE and HaCaT keratinocytes. Pharmacologic and genetic inhibition demonstrated that cytokine-induced expression of miR-184 was mediated by signal transducer and activation of transcription 3 (STAT3). Argonaute 2 (AGO2), a member of the RNA-induced silencing complex (RISC), is a predicted miR-184 target. Using protein, messenger RNA and reporter analyses, we found that miR-184 regulates the expression of AGO2. We conclude that cytokine-induced miR-184 attenuates AGO2 expression in keratinocytes.

Background.As facial appearance can be readily quantified and skin tissue easily accessed, they could be valuable tools for determining how biological mechanisms influence tissue degeneration with age and, consequently, human health and lifespan. It is unknown, however, whether appearance reflects disease risk or lifespan independently of factors already known to associate with both health and appearance.Methods.In a cross-sectional study, we compared the amount of skin wrinkling on a sun-protected site (upper inner arm) and the facial appearance of 261 offspring (mean age 63.2 y) of nonagenarian siblings with 253 age-matched controls (mean age 62.7 y), all with no reported disease history. We next examined whether any appearance features that significantly associated with familial longevity also associated with the Framingham cardiovascular disease (CVD) risk score. All analyses were adjusted for chronological age, smoking, photodamage, and body mass index.Results.Female and male offspring had reduced upper inner arm skin wrinkling (p =. 03 and p

The recognition of the roles of interleukins (IL)-12 and IL-23 in the development of psoriasis is an important advance in the understanding, and the subsequent management, of this chronic inflammatory disease. Two human anti-p40 monoclonal antibodies targeting both IL-12 and IL-23 via their shared p40 subunit have been developed: briakinumab and ustekinumab. Recent Phase 2 and Phase 3 trials have illustrated the benefits of briakinumab (in Phase 3 clinical development) and ustekinumab (approved in the EU, and also in other territories worldwide) in the treatment of moderate to severe plaque psoriasis. Available data indicate that a strategy targeting the IL-12 p40 subunit has considerable advantages over targeting of tumour necrosis factor-α, offering rapid onset of efficacy with a favourable dosing regimen (every 12 weeks for ustekinumab). Registries incorporating rigorous pharmacovigilance are now required to further understand the clinical profile of these drugs over long-term use.

The efficacy and safety profile of ustekinumab with up to three years of exposure suggested a favorable benefit-risk profile in patients with moderate to severe psoriasis.To evaluate the safety of ustekinumab in patients with moderate to severe psoriasis treated for up to four years.Safety data were pooled across four Phase II/III randomized controlled trials. Rates over time and cumulative rates of adverse events (AEs), AEs leading to treatment discontinuation, serious adverse events (SAEs), serious infections, malignancies, and major adverse cardiovascular events (MACE) (i.e., cardiovascular death, myocardial infarction [MI], or stroke as adjudicated by an independent panel of academic cardiologists) were evaluated. Observed rates of AEs of interest were compared with those expected in the general (malignancies, MI, and stroke) and psoriasis (serious infections, MI, and stroke) populations.Overall, 3,117 patients were followed for up to four years (6,791 patient-years). Rates of AEs, AEs leading to treatment discontinuation, and SAEs remained stable over time, whereas cumulative rates were generally comparable between patients who received 45 mg and 90 mg of ustekinumab. The rates of AEs of interest also remained stable over time, and cumulative rates per 100 patient-years were 0.80 and 1.32 (serious infections), 0.70 and 0.53 (nonmelanoma skin cancer), 0.63 and 0.61 (other malignancies), and 0.56 and 0.46 (MACE) in patients treated with 45 mg and 90 mg, respectively. Rates of AEs of interest were consistent with those in the general and psoriasis populations.The safety profile of long-term ustekinumab treatment with up to four years of continuous use remains consistent with previous reports, with no evidence of cumulative toxicity.