Search

Background It is increasingly clear that triglyceride-rich lipoproteins are proinflammatory and cause low-grade systemic inflammation. However, it is currently unknown whether elevated plasma triglycerides are causally related to the development of psoriasis, a skin disorder driven by chronic inflammation. Objectives To determine if elevated plasma triglycerides are associated with increased risk of psoriasis in observational and Mendelian randomization analysis. Methods Consecutive individuals from the Copenhagen General Population Study were included. We used plasma triglycerides (n = 108 043) and a weighted triglyceride allele score (n = 92 579) on nine known triglyceride-altering genetic variants. Genetic results were replicated in 337 159 individuals from the UK Biobank. Psoriasis was defined using the International Classification of Diseases, version 10 (ICD-10) code for hospital contact in the main analyses, and prescription of topical antipsoriatics for mild psoriasis in the sensitivity analysis. Results During a follow-up of median (range) 9.3 (0.1–15.1) years from 2003 to 2015 through 2018, 855 (1%) individuals were diagnosed with psoriasis by ICD-10 in the observational analysis and 772 (1%) in the Mendelian randomization analysis. In the observational analysis, the multivariable adjusted hazard ratio for psoriasis by ICD-10 was 1.26 [95% confidence interval (CI) 1.15–1.39] per doubling in plasma triglycerides with a corresponding causal odds ratio of incident psoriasis of 2.10 (95% CI 1.30–3.38). Causality was confirmed from data from the UK Biobank. Results were similar but slightly attenuated when we used topical antipsoriatic prescriptions for mild psoriasis. Conclusions Elevated plasma triglycerides are associated with an increased risk of psoriasis in observational and Mendelian randomization analysis. [ABSTRACT FROM AUTHOR]

It has previously been pointed out that Student's t test, which assumes that samples are drawn from populations with equal standard deviations, can have an inflated Type I error rate if this assumption is violated. Hence it has been recommended that Welch's t test should be preferred. In the context of carrying out gene-wise weighted burden tests for detecting association of rare variants with psoriasis we observe that Welch's test performs unsatisfactorily. We show that if the assumption of normality is violated and observations follow a Poisson distribution, then with unequal sample sizes Welch's t test has an inflated Type I error rate, is systematically biased and is prone to produce extremely low p values. We argue that such data can arise in a variety of real world situations and believe that researchers should be aware of this issue. Student's t test performs much better in this scenario but a likelihood ratio test based on logistic regression models performs better still and we suggest that this might generally be a preferable method to test for a difference in distributions between two samples. This research has been conducted using the UK Biobank Resource. [ABSTRACT FROM AUTHOR]

Objective Whether metformin and its adenosine 5'monophosphate-activated protein kinase (AMPK) activation protect from psoriasis risk is unconcluded. We investigated the effect of AMPK, a pharmacological target of metformin, on the risk of psoriasis and its comorbidities and mortality among participants in the UK Biobank (UKB). Methods To avoid immortal time biases in pharmacoepidemiologic studies, Mendelian randomization was used to infer the AMPK pathway-dependent effects. The cut-off age for distinguishing early-onset/late-onset psoriasis (EOP/LOP) was set at 60 years, based on the incident psoriasis peak in UKB. A genetic instrument comprising 44 single-nucleotide polymorphisms associated with glycated haemoglobin (HbA1c), serving as a proxy for AMPK genetic risk score (negatively associated with AMPK activation), was employed as previously reported in the literature. Log-binomial models were used to estimate the effect size of AMPK regarding relative risk (RR) and 95% CI. Results A total of 407 159 participants were analysed, including 9126 EOP and 3324 LOP. The AMPK genetic risk score was associated with a 12.4% increase in the risk of LOP in men (RR = 1.124, 95% CI: 1.022–1.236). This association was not significant for EOP or women. AMPK genetic risk score exhibited an elevated risk of ischemic heart disease (RR = 1.217, 95% CI 1.062–1.395) in male psoriasis patients. Conclusions AMPK activation may protect against LOPs and associated ischemic heart disease in men. A sex-specific, comorbidity-targeted intervention for psoriasis is needed. [ABSTRACT FROM AUTHOR]

Objectives Juvenile PsA (JPsA) has varied clinical features that are distinctive from other JIA categories. This study investigates whether such features impact patient-reported and clinical outcomes. Methods Children and young people (CYP) were selected if recruited to the Childhood Arthritis Prospective Study, a UK multicentre JIA inception cohort, between January 2001 and March 2018. At diagnosis, patient/parent-reported outcomes (as age-appropriate) included the parental global assessment (10 cm visual analogue scale), functional ability (Childhood Health Assessment Questionnaire (CHAQ)), pain (10 cm visual analogue scale), health-related quality of life (Child Health Questionnaire PF50 psychosocial score), mood/depressive symptoms (Moods and Feelings Questionnaire) and parent psychosocial health (General Health Questionnaire 30). Three-year outcome trajectories have previously been defined using active joint counts, physician and parent global assessments (PGA and PaGA, respectively). Patient-reported outcomes and outcome trajectories were compared in (i) CYP with JPsA vs other JIA categories and (ii) CYP within JPsA, with and without psoriasis via multivariable linear regression. Results There were no significant differences in patient-reported outcomes at diagnosis between CYP with JPsA and non-JPsA. Within JPsA, those with psoriasis had more depressive symptoms (coefficient = 9.8; 95% CI: 0.5, 19.0) than those without psoriasis at diagnosis. CYP with JPsA had 2.3 times the odds of persistent high PaGA than other ILAR categories, despite improving joint counts and PGA (95% CI: 1.2, 4.6). Conclusion CYP with psoriasis at JPsA diagnosis report worse mood, supporting a greater disease impact in those with both skin and joint involvement. Multidisciplinary care with added focus to support wellbeing in children with JPsA plus psoriasis may help improve these outcomes. [ABSTRACT FROM AUTHOR]

Background Coexisting long-term conditions (LTCs) in psoriasis and their potential causal associations with the disease are not well -established. Objectives To determine distinct clusters of LTCs in people with psoriasis and the potential bidirectional causal association between these LTCs and psoriasis. Methods Using latent class analysis, cross-sectional data from people with psoriasis from the UK Biobank were analysed to identify distinct psoriasis-related comorbidity profiles. Linkage disequilibrium score regression (LDSR) was applied to compute the genetic correlation between psoriasis and LTCs. Two-sample bidirectional Mendelian randomization (MR) analysis assessed the potential causal direction using independent genetic variants that reached genome-wide significance (P < 5 × 10–8). Results Five comorbidity clusters were identified in a population of 10 873 people with psoriasis. LDSR revealed that psoriasis was positively genetically correlated with heart failure [genetic correlation (rg) = 0.23, P = 8.8 × 10−8], depression (rg = 0.12, P = 2.7 × 10−5), coronary artery disease (CAD; rg = 0.15, P = 2 × 10−4) and type 2 diabetes (rg = 0.19, P = 3 × 10−3). Genetic liability to CAD was associated with an increased risk of psoriasis [inverse variance weighted (IVW) odds ratio (ORIVW) 1.159, 95% confidence interval (CI) 1.055–1.274; P = 2 × 10−3]. The MR pleiotropy residual sum and outlier (MR-PRESSO; ORMR-PRESSO 1.13, 95% CI 1.042–1.228; P = 6 × 10−3) and the MR-robust adjusted profile score (RAPS) (ORMR-RAPS 1.149, 95% CI 1.062–1.242; P = 5 × 10−4) approaches corroborate the IVW findings. The weighted median (WM) generated similar and consistent effect estimates but was not statistically significant (ORWM 1.076, 95% CI 0.949–1.221; P = 0.25). Evidence for a suggestive increased risk was detected for CAD (ORIVW 1.031, 95% CI 1.003–1.059; P = 0.03) and heart failure (ORIVW 1.019, 95% CI 1.005–1.033; P = 9 × 10−3) in those with a genetic liability to psoriasis; however, MR sensitivity analyses did not reach statistical significance. Conclusions Five distinct clusters of psoriasis comorbidities were observed with these findings to offer opportunities for an integrated approach to comorbidity prevention and treatment. Coexisting LTCs share with psoriasis common genetic and nongenetic risk factors, and aggressive lifestyle modification in these people is anticipated to have an impact beyond psoriasis risk. Genetically predicted CAD is possibly associated with an increased risk of psoriasis, altering our prior knowledge. [ABSTRACT FROM AUTHOR]

The impact of polysocial risk score (PsRS), a composite measure of multiple social risk factors, on the development of psoriasis remains unclear. Moreover, the potential modifying effects of lifestyle and genetic susceptibility on the relationship between PsRS and psoriasis risk require further exploration. This was a prospective cohort study conducted among UK Biobank. In this study, we analyzed 331,631 participants enrolled in the UK Biobank cohort. To derive the PsRS, we utilized a summative strategy, amalgamating six social determinants of health derived from three domains: socio-economic status, psychosocial factors, and neighborhood and living environment consistently linked to incident psoriasis. Cox proportional hazard models were used to assess the associations between PsRS and psoriasis incidence. Furthermore, we constructed a lifestyle score and a genetic risk score to explore the potential modifying effects of these factors on the relationship between PsRS and psoriasis risk. Compared with individuals with a low PsRS (≤1), those with intermediate PsRS (2–4) and high PsRS (≥5) had 1.20 (95% confidence interval [CI], 1.06–1.36) and 1.53 (95% CI, 1.31–1.78) times higher risks of developing psoriasis, respectively. Our findings revealed an additive interaction between PsRS and genetic susceptibility. Moreover, it was found that individuals with high PsRS and unhealthier lifestyles had a 2.60 times higher risk of developing psoriasis than those with lower PsRS and healthier ones. Our study results imply that an elevated PsRS is linked to a heightened risk of psoriasis, which is further influenced by genetic factors. Our results also indicate that greater social vulnerability and unhealthier lifestyle may synergistically contribute to the additional risk of psoriasis. [ABSTRACT FROM AUTHOR]

The use of remote consultations via telephone or video can contribute to the management of people with psoriasis and has allowed continuity of patient care throughout the SARS-CoV-2 pandemic, though little is known about the patient experience. The present study aimed to provide insights into the views and experiences of people with psoriasis and psoriatic arthritis on their remote consultations during the SARS-CoV-2 pandemic and develop guidance for patients and healthcare professionals on how to optimise future remote consultations. We conducted a cross-sectional, on-line survey of people with psoriasis and psoriatic arthritis. Data were analysed using descriptive statistics and Thematic Analysis. Overall, 126 people reported experiences of telephone (92%) or video (8%) consultations. Most participants were satisfied with (78%), and were happy for, remote consultations to continue (21%); few were not (5%). Others did not always want remote consultations (39%) and preferred alternating with face-to-face consultations (18%). Some wanted remote care during the pandemic only (17%). Five themes were identified: (1) Advantages of Remote Consultations; (2) Disadvantages of Remote Consultations plus sub-themes (2.1) Practical Issues and (2.2) the Absence of Non-Verbal Cues and Emotions; (3) Serving a Purpose; and (4) A 'Good' Remote Consultation; and (5) Advice to Other Patients. Remote consultations form an important part of psoriatic disease management, mainly for routine follow-up appointments in patients with stable disease, and in addition to face-to-face consultations. Additional skills training for clinicians could improve the quality of remote consultations. [ABSTRACT FROM AUTHOR]

Background: Observational studies have suggested that childhood body mass index (BMI) is associated with the risk of psoriasis. However, their causal relationship remains unclear. In this investigation, we aimed to determine whether an association exists between childhood BMI and psoriasis. Methods: Using summary statistics for childhood BMI of European descent from publicly available GWAS meta‐analyses (n = 39 620), we conducted Mendelian randomization (MR) research using the inverse variance weighting (IVW), weighted median, and MR‐Egger regression techniques. The outcome was a genome‐wide association studies (GWAS) for the self‐reported non‐cancer disease classification psoriasis in the UK Biobank population (total n = 337 159; case = 3871; control = 333 288). Results: We selected instrumental variables from 16 single‐molecule polymorphisms that attained genome‐wide significance in GWAS on childhood BMI. Using the IVW method, our findings supported a causal relationship between childhood BMI and psoriasis (beta = 0.003, standard error [SE] = 0.001, p = 0.006). Using MR‐Egger regression analysis, we evaluated the potential for directional pleiotropy to bias our results (intercept = 0.00039, p‐value = 0.247) and found no causal relationship between childhood BMI and psoriasis (beta = −0.002, SE = 0.004, p = 0.625). The weighted median method, however, provided proof of a causal relationship (beta = 0.003, SE = 0.001, p = 0.029). Cochran's Q test and the funnel plot revealed little proof of heterogeneity or asymmetry, indicating the lack of directional pleiotropy. Conclusion: According to the findings of the MR analysis, an increased childhood BMI may be linked to a higher likelihood of psoriasis. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis (PsO) is associated with the development of psoriatic arthritis (PsA). Patients with PsO often experience pre-PsA musculoskeletal (MSK) symptoms, leading to potential structural damage and substantial disease burden with impact on function. The objective of this study is to describe prevalence rates and evidence of MSK symptoms, including incidence of comorbid PsA diagnosis, in patients newly diagnosed with PsO and identify factors associated with PsA diagnosis. Methods: This retrospective analysis included administrative claims from the Optum Research Database for adult patients with a new PsO diagnosis between January 2008 and February 2019. Eligible patients had ≥ 2 claims for PsO on unique dates, were aged ≥ 18 years at the date of the first claim with a diagnosis of PsO (index date), and had continuous enrollment with medical and pharmacy coverage for 12 months before (baseline period) and ≥ 12 months following the index date. Primary outcomes were incidence of comorbid PsA diagnosis, prevalence of MSK symptoms other than PsA, and evidence of MSK symptoms collected at baseline and assessed in 12-month intervals through 60 months. Results: Of the 116,203 patients with newly diagnosed PsO, 110,118 were without baseline comorbid PsA. High prevalence rates of MSK symptoms among patients with only PsO were seen at baseline (47.1%), 12 months (48.2%), and 60 months (82.1%). Patient age, baseline MSK symptoms, and baseline MSK symptom–related healthcare utilization were associated with increased hazard of a PsA diagnosis. Conclusion: Increased prevalence rates of MSK symptoms and burden are experienced by patients newly diagnosed with PsO through 60 months of follow-up. Several baseline factors were associated with increased risk of PsA diagnosis. Plain Language Summary: A Study to Look at Symptoms of Muscles, Joints, and Bones in Patients with Psoriasis and Whether They Can Predict a Diagnosis of Psoriatic Arthritis Psoriasis is an inflammatory skin disease that results in areas of significant itchiness, pain, and scaling, and ultimately decreases patient quality of life. Psoriasis affects approximately 2–4% of the general US population and 1.3–2.2% of the UK population. Some patients with psoriasis may experience musculoskeletal symptoms and may go on to develop psoriatic arthritis. The goal of this study was to determine the frequency of patients with psoriasis who experienced complaints of musculoskeletal pain prior to and/or following their psoriasis diagnosis, and whether these were associated with further probability of developing psoriatic arthritis. Using a large US-based database with data from approximately 115,000 patients with newly diagnosed psoriasis, we determined the percentage of newly diagnosed psoriasis patients with existing musculoskeletal pain complaints within 12 months of their initial diagnosis. We found that 47% of newly diagnosed patients had previous musculoskeletal pain complaints, with joint pain, back pain, and overall fatigue representing the most common forms. Notably, psoriasis patients with previous joint pain were approximately 50% more likely to develop psoriatic arthritis compared with patients with no previous joint pain. Furthermore, patients with previous other forms of arthritis were nearly twice as likely to develop psoriatic arthritis. This study provides additional support that existing musculoskeletal pain in patients with newly diagnosed psoriasis may predict the potential future onset of psoriatic arthritis. These findings will help guide primary care physicians, dermatologists, and rheumatologists in understanding the importance of earlier detection of psoriatic arthritis to provide more appropriate care. [ABSTRACT FROM AUTHOR]

Mendelian randomization (MR) analysis was performed to explore the effect of psoriasis on lipid metabolism traits and myocardial infarction (MI) risk and to analyze the proportion of the mediatory effect of lipid metabolism traits. Publicly accessible summary-level data for psoriasis, lipid metabolism traits, and MI were provided by the genome-wide association studies (GWASs) of the FinnGen Biobank, UK Biobank, and CARDIoGRAMplusC4D, respectively. A two-sample MR was carried out to evaluate the association of psoriasis with lipid metabolism traits and MI. Furthermore, the current research focused on determining if the impact of psoriasis on MI is mediated by lipid metabolism traits. The outcomes of the random effect inverse-variance-weighted (IVW) technique indicated a substantial link between genetically predicted psoriasis and a higher risk of low-density lipoprotein (LDL) cholesterol (OR: 1.006, 95% CI: 1.005–1.007, p = 0.024), apolipoprotein B (OR: 1.018, 95% CI: 1.010–1.026, p = 0.015), lipoprotein A (OR: 1.006, 95% CI: 1.002–1.010, p = 0.039), and MI (OR: 1.066, 95% CI: 1.014–1.121, p = 0.012). The percentages of the mediatory effect of LDL cholesterol, apolipoprotein B, and lipoprotein A under psoriasis conditions on MI risk was 7.4%, 10.2%, and 4.1%, respectively. Psoriasis was causally linked to an elevated risk of lipid metabolism levels and MI. This study further demonstrated that LDL cholesterol, apolipoprotein B, and lipoprotein A mediated the effect of psoriasis on MI risk. And timely lipid-lowering treatment should be given to MI patients. [ABSTRACT FROM AUTHOR]

Introduction: Previous research has shown associations between eczema and psoriasis and anxiety and depression. We investigated whether associations are consistent across different settings of ascertainment for depression and anxiety, including interview and survey responses from UK Biobank (a large longitudinal cohort recruiting individuals aged 40– 69 years between 2006– 2010), and linked primary care data, with the aim of drawing more reliable conclusions through triangulation.Methods: In cross-sectional studies, we estimated associations between eczema or psoriasis and anxiety or depression, defining anxiety or depression as 1) self-reported previous diagnosis at UK Biobank recruitment interview; 2) PHQ-9/GAD-7 score indicating depression or anxiety from a UK Biobank mental health follow-up survey in 2016; and 3) diagnosis in linked primary care electronic health record data.Results: We analysed 230,047 people with linked Biobank and primary care data. We found poor agreement between the data sources for eczema, psoriasis, anxiety, and depression. Eg, 9474 had a previous eczema diagnosis in primary care data, 4069 self-reported previous eczema diagnosis at the UK biobank interview, and 1536 had eczema in both data sources (for depression 40,455; 13,320; and 9588 respectively). Having eczema or psoriasis (recorded in primary care or baseline interview) was associated with higher odds of anxiety and depression. Eg, the adjusted odds ratio for depression comparing those with eczema to those without was greater than 1 when defining the outcome from 1) the recruitment interview (1.36, 95% confidence interval 1.27– 1.45); 2) the follow-up survey (1.24, 1.09– 1.39), and 3) primary care records (1.56, 1.50– 1.62).Discussion: Our findings support increased prevalence of mental illness in people with psoriasis and eczema across multiple data sources, which should be considered in planning of mental health services. However, we found poor agreement in disease ascertainment between settings, with implications for data interpretation in electronic health records. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory skin disease. Dyslipidemia may be a risk factor of psoriasis. But the causal relationship between psoriasis and blood lipid still remains uncertain. Methods: The two data of blood lipid were obtained from UK Biobank (UKBB) and Global Lipid Genetics Consortium Results (GLGC). The primary and secondary database were from large publicly available genome-wide association study (GWAS) with more than 400,000 and 170,000 subjects of European ancestry, respectively. The psoriasis from Finnish biobanks of FinnGen research project for psoriasis, consisting of 6,995 cases and 299,128 controls. The single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) were used to assess the total and direct effects of blood lipid on psoriasis risk. Results: SVMR estimates in primary data of blood lipid showed low-density lipoprotein cholesterol (LDL-C) (odds ratio (OR): 1.11, 95%, confidence interval (CI): 0.99-1.25, p = 0.082 in stage 1;OR: 1.15, 95% CI: 1.05-1.26, p = 0.002 in stage 2; OR: 1.15, 95%CI: 1.04-1.26, p = 0.006 in stage 3) and triglycerides (TG) (OR: 1.22, 95% CI: 1.10-1.35, p = 1.17E-04 in stage 1; OR: 1.15, 95% CI: 1.06-1.24, p =0.001 in stage 2; OR: 1.14, 95% CI: 1.05-1.24, p = 0.002 in stage 3) had a highly robust causal relationship on the risk of psoriasis. However, there were no robust causal associations between HDL-C and psoriasis. The SVMR results in secondary data of blood lipid were consistent with the primary data. Reverse MR analysis showed a causal association between psoriasis and LDL-C (beta: -0.009, 95% CI: -0.016--0.002, p = 0.009) and HDL-C (beta: -0.011, 95% CI: -0.021--0.002, p = 0.016). The reverse causation analyses results between psoriasis and TG did not reach significance. In MVMR of primary data of blood lipid, the LDL-C (OR: 1.05, 95% CI: 0.99-1.25, p = 0.396 in stage 1; OR: 1.07, 95% CI: 1.01-1.14, p = 0.017 in stage 2; OR: 1.08, 95% CI: 1.02-1.15, p = 0.012 in stage 3) and TG (OR: 1.11, 95% CI: 1.01-1.22, p = 0.036 in stage 1; OR: 1.09, 95% CI: 1.03-1.15, p = 0.002 in stage 2; OR: 1.07, 95% CI: 1.01-1.13 p = 0.015 in stage 3) positively correlated with psoriasis, and there had no correlation between HDL-C and psoriasis. The results of the secondary analysis were consistent with the results of primary analysis. Conclusions: Mendelian randomization (MR) findings provide genetic evidence for causal link between psoriasis and blood lipid. It may be meaningful to monitor and control blood lipid level for a management of psoriasis patients in clinic. [ABSTRACT FROM AUTHOR]

Objectives PsA is one of the most serious comorbidities associated with psoriasis. While the early intervention in PsA is demanded, risk factors of PsA development are not well-known. This is the first prospective study to evaluate the clinical significance of nailfold capillary (NFC) changes in patients with psoriasis. Methods We conducted a prospective cohort study in a population of 449 psoriasis patients who had not been treated with systemic therapy or topical finger therapy. NFCs were observed by dermoscopy and capillaroscopy, and the correlation of NFC abnormalities, including nailfold bleeding (NFB) and enlarged capillaries, with the prevalence of PsA, incidence of new PsA, and serum levels of TNF-a, IL-17A and IL-23 were analysed. Results Detailed examination at the time of inclusion revealed that of 449 patients, 236 had Psoriasis vulgaris (PsV) and 213 had PsA. Both NFB and enlarged capillaries were significantly more frequent in patients with PsA (34.7% vs 84.5%, P  < 0.0001; 25.4% vs 100%, P  < 0.0001). In addition, PsV patients were prospectively observed before they developed PsA (mean 21 months, 95% CI 2, 77 months). Multivariate analysis suggested that the appearance of NFB and enlarged capillaries was a predictor of PsA development (HR 2.75, 95% CI 1.38, 5.47 and HR 4.49, 95% CI 2.25, 8.96, respectively). The degree of NFC abnormalities also correlated with the severity of PsA and serum cytokine levels. Conclusions NFC abnormalities were suggested to be a predictor of PsA in psoriasis patients, and at the same time, its degree could be an indicator of disease severity. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a chronic, inflammatory, immune-mediated disease. This study assessed the time at which patients switched from a conventional oral systemic treatment to a biologic therapy; patient clinical and quality of life (QoL) outcomes associated with oral systemic treatments; and the proportion of patients who persisted on oral therapy (nonswitchers), despite reported suboptimal clinical and QoL outcomes. Methods: This data analysis used the Adelphi Real World Psoriasis Disease Specific Programme, a non-interventional, retrospective, cross-sectional survey conducted in the USA, France, Germany, and United Kingdom (August 2018–April 2019). Kaplan–Meier (KM) analysis assessed switching from oral to biologic therapy in patients treated ≥ 3 years at survey completion (n = 597). The severity of psoriasis was reported by physicians as the percentage of body surface area (BSA) affected by psoriasis. Dermatology Life Quality Index (DLQI) scores were calculated for three groups: nonswitchers who met treatment failure criteria, nonswitchers who did not meet failure criteria, and switchers to a biologic therapy. Results: In KM analysis, approximately 50% of the patient population switched by 24 months. A substantial portion of nonswitchers continued to have moderate-to-severe psoriasis. Among nonswitchers, 57–77% had BSA ≥ 3% and 16–24% had BSA ≥ 10% at the time of the survey compared with 37% of switchers who had BSA of ≥ 3% and 9% who had BSA of ≥ 10%. QoL was poor among nonswitchers. The mean [standard deviation (SD)] DLQI scores for nonswitchers meeting treatment failure criteria, nonswitchers not meeting failure criteria, and switchers were 6.11 (4.55), 2.62 (3.29), and 2.25 (4.23), respectively. Conclusion: There is a clear unmet need for more effective oral therapies, and further research into the reasons for patients remaining undertreated, which may include patient preference for oral treatments (despite lack of response), contraindications, or insurance/formulary-related barriers to access, are needed. Plain Language Summary: Psoriasis is a common skin disease that causes itchy, painful, scaly sores. Patients may feel stigmatized, which can impact their quality of life and productivity. About 1 in 5 patients have severe psoriasis, which is harder to treat and may require pills or shots. Both shots and pills are effective at treating psoriasis; however, many patients choose to continue taking pills, even if their psoriasis worsens, for reasons including a desire to avoid needles. We described patients with moderate-to-severe psoriasis who started on pills and either remained on pills or switched to shots by the time of the survey. We looked at the reasons they gave for switching, as well as at quality of life measures reported by the patients. To do this, we analyzed data from a survey called the Adelphi Real World Psoriasis Disease Specific Programme. This survey was conducted among doctors who treat skin diseases and their patients. Participating doctors and patients from the USA, France, Germany, and the United Kingdom were asked questions about the patients' health and how psoriasis affects their lives. Survey results showed that nearly half of patients switched to shots by 24 months, and most who switched cited treatment failure as the reason. Those who continued to take their pills despite having more severe psoriasis symptoms had more itching and pain and had lower quality of life than those who switched to shots. This suggests that there is a need for more effective oral treatments for patients with psoriasis. [ABSTRACT FROM AUTHOR]

The risk of significant liver fibrosis from prolonged methotrexate (MTX) exposure has been estimated at around 5%, prompting intensive monitoring strategies. However, the evidence is derived from retrospective studies that under-reported risk factors for liver disease. We evaluated the risk of long-term MTX therapy on liver fibrosis in a longitudinal cohort study using two non-invasive markers. Between 2014-2021, adult patients diagnosed with rheumatoid arthritis (RA) or psoriasis for ≥2 years were recruited prospectively from six UK sites. The MTX group included patients who received MTX for ≥6 months, whereas the unexposed group included those who never received MTX. All patients underwent full liver profiling, with transient elastography (TE) and enhanced liver fibrosis (ELF) marker measurements. A total of 999 patients (mean age 60.8 ± 12 years, 62.3% females) were included. Of 976 with valid TE values, 149 (15.3%) had liver stiffness ≥7.9 kPa. Of 892 with a valid ELF, 262 (29.4%) had ELF ≥9.8. Age and BMI were independently associated with elevated liver stiffness and ELF. Neither MTX cumulative dose nor duration was associated with elevated liver stiffness. Diabetes was the most significant risk factor associated with liver stiffness ≥7.9 kPa (adjusted odds ratio = 3.19; 95% CI 1.95–5.20; p < 0.001). Regular use of non-steroidal anti-inflammatory drugs showed the strongest association with ELF ≥9.8 (odds ratio = 1.76; 95% CI 1.20–2.56; p = 0.003), suggesting the degree of joint inflammation in RA may confound ELF as a non-invasive marker of liver fibrosis. The risk of liver fibrosis attributed to MTX itself might have been previously overestimated; there is a need to consider modifying current monitoring guidelines for MTX. Current guidelines recommend intensive (2-3 monthly) monitoring strategies for patients on long-term methotrexate therapy due to the potential risk of liver fibrosis. Evaluation of the association using two validated non-invasive markers of liver fibrosis, liver stiffness and enhanced liver fibrosis score, in a large cohort of patients with rheumatoid arthritis or psoriasis shows that the reported risk has previously been overestimated. The clinical focus should be to improve patients' metabolic risk factors, diabetes and BMI, that are independently associated with liver stiffness. There is a need to consider modifying current treatment monitoring guidelines for methotrexate. [Display omitted] • Guidelines have recommended intensive monitoring based on the reported risk of liver fibrosis linked to methotrexate. • Using non-invasive markers, we show that the risk of liver fibrosis linked to long-term methotrexate may have been overestimated. • Our findings support the need to improve patients' metabolic risk factors, which are significantly associated with liver fibrosis. • In patients with rheumatoid arthritis, transient elastography is more reliable to screen for liver fibrosis than ELF. [ABSTRACT FROM AUTHOR]

Objectives: Obesity is a common (30%–40%) comorbidity of psoriasis. Weight loss is shown to improve the severity of psoriasis; however, little is known about the factors that may influence successful weight loss in the context of obesity and psoriasis. The current qualitative study aimed to explore the obesity‐associated beliefs, perceptions, and behaviours related to weight loss in psoriasis. Preferences for a weight loss intervention were also explored. Design: Qualitative in‐depth semi‐structured interviews were conducted with 24 adults (62.5% male) with moderate‐to‐severe psoriasis and obesity (mean body mass index = 35.2 kg/m2, SD = 4.1), recruited through a patient organization website in the UK. Data were analysed using inductive thematic analysis. Results: Most participants viewed psoriasis as unrelated to obesity. A well‐controlled psoriasis and improvements in psoriasis symptoms were considered as major motivators for engaging in a weight loss program by individuals who viewed psoriasis and obesity as related conditions. Comfort eating was perceived as an escape strategy from the psoriasis‐induced negative emotions. Participants shared their dissatisfaction with current weight loss recommendations which were too generic. They suggested that a desirable weight loss program would require both emotional and behavioural support, with an emphasis on psoriasis' burden. Conclusion: The findings accentuate the importance of (1) clinicians discussing the link between obesity and psoriasis with patients, (2) weight loss advice to include both behavioural and emotional support, and (3) a weight loss advice to consider the psoriasis burden and the perceived barriers which may potentially lead to improved outcomes to obesity management in psoriasis. [ABSTRACT FROM AUTHOR]

Objectives To examine associations between PsA and psoriasis vs lifestyle factors and comorbidities by triangulating observational and genetic evidence. Methods We analysed cross-sectional data from the UK Biobank (1836 PsA, 8995 psoriasis, 36 000 controls) to describe the association between psoriatic disease and lifestyle factors (including BMI and smoking) and 15 comorbidities [including diabetes and coronary artery disease (CAD)] using logistic models adjusted for age, sex and lifestyle factors. We applied bidirectional Mendelian randomization (MR) to genome-wide association data (3609 PsA and 7804 psoriasis cases, up to 1.2 million individuals for lifestyle factors and 757 601 for comorbidities) to examine causal direction, using the inverse-variance weighted method. Results BMI was cross-sectionally associated with risk of PsA (OR 1.31 per 5 kg/m2 increase; 95% CI 1.26, 1.37) and psoriasis (OR 1.23; 1.20, 1.26), with consistent MR estimates (PsA OR 1.38; 1.14, 1.67; psoriasis OR 1.36; 1.18, 1.58). In both designs, smoking was more strongly associated with psoriasis than PsA. PsA and psoriasis were cross-sectionally associated with diabetes (OR 1.35 and 1.39, respectively) and CAD (OR 1.56 and 1.38, respective). Genetically predicted glycated haemoglobin (surrogate for diabetes) increased PsA risk (OR 1.18 per 6.7 mmol/mol increase; 1.02, 1.36) but not psoriasis. Genetic liability to PsA (OR 1.05; 1.003, 1.09) and psoriasis (OR 1.03; 1.001, 1.06) were associated with increased risk of CAD. Conclusion Observational and genetic evidence converge to suggest that BMI and glycaemic control are associated with increased psoriatic disease risk, while psoriatic disease is associated with increased CAD risk. Further research is needed to understand the mechanism of these associations. [ABSTRACT FROM AUTHOR]

Background: Existing research exploring associations between atopic eczema (AE) or psoriasis, and severe mental illness (SMI – ie, schizophrenia, bipolar disorder, other psychoses) is limited, with longitudinal evidence particularly scarce. Therefore, temporal directions of associations are unclear. We aimed to investigate associations between AE or psoriasis and incident SMI among adults. Methods: We conducted matched cohort studies using primary care electronic health records (January 1997 to January 2020) from the UK Clinical Practice Research Datalink GOLD. We identified two cohorts: 1) adults (≥ 18 years) with and without AE and 2) adults with and without psoriasis. We matched (on age, sex, general practice) adults with AE or psoriasis with up to five adults without. We used Cox regression, stratified by matched set, to estimate hazard ratios (HRs) comparing incident SMI among adults with and without AE or psoriasis. Results: We identified 1,023,232 adults with AE and 4,908,059 without, and 363,210 with psoriasis and 1,801,875 without. After adjusting for matching variables (age, sex, general practice) and potential confounders (deprivation, calendar period) both AE and psoriasis were associated with at least a 17% increased hazard of SMI (AE: HR=1.17,95% CI=1.12– 1.22; psoriasis: HR=1.26,95% CI=1.18– 1.35). After additionally adjusting for potential mediators (comorbidity burden, harmful alcohol use, smoking status, body mass index, and, in AE only, sleep problems and high-dose glucocorticoids), associations with SMI did not persist for AE (HR=0.98,95% CI=0.93– 1.04), and were attenuated for psoriasis (HR=1.14,95% CI=1.05– 1.23). Conclusion: Our findings suggest adults with AE or psoriasis are at increased risk of SMI compared to matched comparators. After adjusting for potential mediators, associations with SMI did not persist for AE, and were attenuated for psoriasis, suggesting that the increased risk may be explained by mediating factors (eg, sleep problems). Our research highlights the importance of monitoring mental health in adults with AE or psoriasis. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a chronic inflammatory disease of the skin. A few studies have shown that psoriasis is an immune-mediated disease in which multiple immune cells play crucial roles. However, the association between circulating immune cells and psoriasis remains elusive. Methods: To explore the role of circulating immune cells in psoriasis, 361,322 individuals from the UK Biobank (UKB) and 3,971 patients with psoriasis from China were included to investigate the association between white blood cells and psoriasis via an observational study. Genome-wide association studies (GWAS) and Mendelian randomization (MR) were used to evaluate the causal relationship between circulating leukocytes and psoriasis. Results: The risk of psoriasis increased with high levels of monocytes, neutrophils, and eosinophils (relative risks and 95% confidence intervals, respectively: 1.430 (1.291-1.584) for monocytes, 1.527 (1.379-1.692) for neutrophils, and 1.417 (1.294-1.551) for eosinophils). Upon further MR analysis, eosinophils showed a definite causal relationship with psoriasis (odds ratio of inverse-variance weighted: 1.386, 95% confidence intervals: 1.092-1.759) and a positive correlation with the psoriasis area and severity index (PASI) score (P = 6.6 x 10-5). The roles of the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) in psoriasis were also assessed. More than 20,000 genetic variations associated with NLR, PLR, and LMR were discovered in a GWAS analysis using the UKB data. Following adjustment for covariates in the observational study, NLR and PLR were shown to be risk factors for psoriasis, whereas LMR was a protective factor. MR results indicated that there was no causal relationship between these three indicators and psoriasis; however, NLR, PLR, and LMR correlated with the PASI score (NLR: rho = 0.244, P = 2.1 x 10-21; PLR: rho = 0.113, P = 1.4 x 10-5; LMR: rho = -0.242, P = 3.5x10-21). Discussion: Our findings revealed an important association between circulating leukocytes and psoriasis, which is instructive for the clinical practice of psoriasis treatment. [ABSTRACT FROM AUTHOR]

Psoriasis is an immune‐mediated inflammatory skin disease affecting approximately 2% of the UK population. Its pathogenesis is suggested to be an outcome of genetic and environmental interplay. People with psoriasis have an increased likelihood of developing other conditions such as type 2 diabetes and cardiovascular disease. Systemic inflammation is hypothesised to be the common link between psoriasis and cardio‐metabolic diseases. Emerging evidence shows diet as a potential therapeutic adjunct in the management of psoriasis. The Diet and Psoriasis Project (DIEPP) aims to investigate whether dietary factors are related to psoriasis severity by conducting an observational study followed by a dietary intervention trial, to assess the effect of the Mediterranean diet (MedD) and time‐restricted eating (TRE) on psoriasis. This review article will explore the potential mechanisms by which the MedD and TRE may exert protective effects on psoriasis, evaluate the current evidence, and outline the design of the DIEPP. Given the early‐stage evidence, we hope to be able to build knowledge to derive medically approved dietary recommendations and contribute to the research gaps exploring the role of diet and psoriasis. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption and smoking have been reported to be associated with psoriasis risk. However, a conclusion with high‐quality evidence of causality could not be easily drawn from regular observational studies. Objectives: This study aims to assess the causal associations of alcohol consumption and smoking with psoriasis. Methods: Genome‐wide association study (GWAS) summary‐level data for alcohol consumption (N = 941 280), smoking initiation (N = 1 232 091), cigarettes per day (N = 337 334) and smoking cessation (N = 547 219) was obtained from the GSCAN consortium (Sequencing Consortium of Alcohol and Nicotine use). The GWAS results for lifetime smoking (N = 462 690) were obtained from the UK Biobank samples. Summary statistics for psoriasis were obtained from a recent GWAS meta‐analysis of eight cohorts comprising 19 032 cases and 286 769 controls and the FinnGen consortium, comprising 4510 cases and 212 242 controls. Linkage disequilibrium score regression was applied to compute the genetic correlation. Bidirectional Mendelian randomization (MR) analyses were conducted to determine casual direction using independent genetic variants that reached genome‐wide significance (P < 5 × 10–8). Results: There were genetic correlations between smoking and psoriasis. MR revealed a causal effect of smoking initiation [odds ratio (OR) 1·46, 95% confidence interval (CI) 1·32–1·60, P = 6·24E‐14], cigarettes per day (OR 1·38, 95% CI 1·13–1·67, P = 0·001) and lifetime smoking (OR 1·96, 95% CI 1·41–2·73, P = 7·32E‐05) on psoriasis. Additionally, a suggestive causal effect of smoking cessation on psoriasis was observed (OR 1·39, 95% CI 1·07–1·79, P = 0·012). We found no causal relationship between alcohol consumption and psoriasis (P = 0·379). The reverse associations were not statistically significant. Conclusions: Our findings provide causal evidence for the effects of smoking on psoriasis risk. What is already known about this topic?Alcohol consumption and smoking have been reported to be associated with psoriasis risk.Whether alcohol consumption and smoking have a causal effect on psoriasis risk remains unclear. What does this study add?This Mendelian randomization study shows a causal association between smoking, but not alcohol consumption, and the risk of developing psoriasis.Restricting smoking could be helpful in reducing the burden of psoriasis. [ABSTRACT FROM AUTHOR]

The article focuses on psoriasis which is an auto-immune, inflammatory condition that for many is mild and manageable with basic over the counter (OTC) medicine. It mentions that it is best to examine the patient undressed but an examination can also be achieved in primary care by rolling up clothing and examining the body systematically. It informs that psoriatic arthritis is more common in people with type-1 early onset psoriasis (chronic plaque psoriasis).

Background: The diagnosis of psoriasis may be missed or delayed in primary care settings. Aim: To examine trends in healthcare events before a diagnosis of psoriasis. Design and setting: Two matched case–control studies using electronic healthcare records delineated from the Clinical Practice Research Datalink (CPRD GOLD and Aurum) in the UK. Method: Individuals aged ≥18 years with an incident diagnosis of psoriasis (case group) between 1 January 2010 and 29 December 2017 were identified and matched by age, sex, and general practice with six individuals without psoriasis (control group). Healthcare activities were examined and annual incidence rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for 10 years before the index date were compared between case and control groups. Results: There were 17 320 people with psoriasis and 99 320 controls included from CPRD GOLD, and 11 442 people with psoriasis and 65 840 controls extracted from CPRD Aurum. Data from CPRD GOLD showed that people with psoriasis were up to eight times more likely to be diagnosed with pityriasis rosea at 6 months (IRR 7.82, 95% CI = 4.09 to 14.95) before the index date than the control group. The case group were twice as likely to be diagnosed with eczema (IRR 1.90, 95% CI = 1.76 to 2.05) or tinea corporis (IRR 1.99, 95% CI = 1.74 to 2.27) 1 year before the index date. The case group were more likely to report dry skin, rash, skin texture changes, and itching than the control group up to 5 years before the index date. The most frequently reported clinical feature was rash with an IRR of 2.71 (95% CI = 2.53 to 2.92) at 1 year before the index date. The case group were prescribed topical corticosteroids (IRR 1.97, 95% CI = 1.88 to 2.07) or topical antifungals (IRR 1.92, 95% CI = 1.78 to 2.07) in the year before the index date twice as often as those in the control group. Conclusion: Findings suggest that the diagnosis of psoriasis may be missed or delayed in a UK primary care setting for up to 5 years for some individuals, hence leading to a potentially detrimental delay in establishing an appropriate treatment regimen. [ABSTRACT FROM AUTHOR]

Introduction: As with most medicines historically, clinicians prescribing tildrakizumab have relied on information derived from registration studies undertaken in a prospective controlled clinical trial setting. More recently, clinicians, policymakers, and commissioners increasingly rely on real-world data to inform both policy and practice. Methods: A retrospective real-world data study was undertaken at four specialist dermatology departments in the United Kingdom. All adult patients treated with tildrakizumab for moderate-to-severe plaque psoriasis were included, with data being collected for 122 patients. Results: Psoriatic patients on tildrakizumab tended to be overweight (median body mass index of 32 (range 19–59) (n = 61); 26/68 (38%) < 90 kg, 32/68 (47%) between 90 and 120 kg, and 10/68 (15%) > 120 kg). The study population had high levels of comorbidities (83/116, 72%), multiple special sites (39/117, 33%), and histories of biological treatments (81/100, 81%). Most patients (61/80, 76%) initiated on tildrakizumab were switched from another biological treatment. Tildrakizumab was effective, with 91/122 (75%) patients remaining on treatment for the duration of the study—a median of 12 months per patient (range 1–29 months)—and achieving a change in median Psoriasis Area and Severity Index (PASI) from 12 to 0.35 and in Dermatology Life Quality Index (DLQI) from 20 to 0. The response rate was 57/66 (86%) when tildrakizumab was used as the first- or second-line biologic compared to 19/31 (61%) when used as the third- to seventh-line. Thirty-three (78.6%) patients over 90 kg of weight received the 200-mg dose of tildrakizumab. All but one (n = 8) patient with body weight over 120 kg maintained response over time. There was one treatment discontinuation; a patient who had a local sensitivity reaction. Conclusions: In UK clinical practice, tildrakizumab was well tolerated and effective at doses of 100 mg or 200 mg in a range of patient phenotypes. [ABSTRACT FROM AUTHOR]

Despite increased understanding about psoriasis pathophysiology, currently there is a lack of predictive computational models. We developed a personalisable ordinary differential equations model of human epidermis and psoriasis that incorporates immune cells and cytokine stimuli to regulate the transition between two stable steady states of clinically healthy (non-lesional) and disease (lesional psoriasis, plaque) skin. In line with experimental data, an immune stimulus initiated transition from healthy skin to psoriasis and apoptosis of immune and epidermal cells induced by UVB phototherapy returned the epidermis back to the healthy state. Notably, our model was able to distinguish disease flares. The flexibility of our model permitted the development of a patient-specific "UVB sensitivity" parameter that reflected subject-specific sensitivity to apoptosis and enabled simulation of individual patients' clinical response trajectory. In a prospective clinical study of 94 patients, serial individual UVB doses and clinical response (Psoriasis Area Severity Index) values collected over the first three weeks of UVB therapy informed estimation of the "UVB sensitivity" parameter and the prediction of individual patient outcome at the end of phototherapy. An important advance of our model is its potential for direct clinical application through early assessment of response to UVB therapy, and for individualised optimisation of phototherapy regimes to improve clinical outcome. Additionally by incorporating the complex interaction of immune cells and epidermal keratinocytes, our model provides a basis to study and predict outcomes to biologic therapies in psoriasis. Author summary: We present a new computer model for psoriasis, an immune-mediated disabling skin disease which presents with red, raised scaly plaques that can appear over the whole body. Psoriasis affects millions of people in the UK alone and causes significant impairment to quality of life, and currently has no cure. Only a few treatments (including UVB phototherapy) can induce temporary remission. Despite our increased understanding about psoriasis, treatments are still given on a 'trial and error' basis and there are no reliable computer models that can a) elucidate the mechanisms behind psoriasis onset or flare and b) predict a patient's response to a course of treatment (e.g., phototherapy) and the likelihood of inducing a period of remission. Our computer model addresses both these needs. First, it explicitly describes the interaction between the immune system and skin cells. Second, our model captures response to therapy at the individual patient level and enables personalised prediction of clinical outcomes. Notably, our model also supports prediction of amending individual UVB phototherapy regimes based on the patient's initial response that include for example personalised delivery schedules (i.e., 3x weekly vs. 5x weekly phototherapy). Therefore, our work is a crucial step towards precision medicine for psoriasis treatment. [ABSTRACT FROM AUTHOR]

Objective: To determine the annual incidence of psoriatic arthritis (PsA) in a United Kingdom primary care population with preexisting psoriasis (PsO) followed prospectively over 2 years after excluding baseline prevalence of existing disease., Methods: Total Burden of Psoriasis (TUDOR; ISRCTN registry: ISRCTN38877516) was a multicenter, prospective, 2-arm parallel-group cluster randomized controlled trial of the early identification of PsA by annual rheumatological assessment (termed "Enhanced Surveillance") vs standard care in people with PsO identified in primary care. Incidence of PsA is reported at 12 months and 24 months using patients from the Enhanced Surveillance arm, which allows for the exclusion of patients with prevalent PsA at baseline., Results: Fourteen of 511 participants attending a 12-month screen developed PsA over that interval, giving an incidence of 2.74/100 patient-years (PYs; 95% CI 1.32-4.16). Another 7/444 participants attending the 24-month visit developed PsA, giving an incidence of 1.58/100 PYs (95% CI 0.42-2.74). The combined incidence over 2 years was 2.20/100 PYs (95% CI 1.27-3.13)., Conclusion: The estimated annual incidence of PsA over a 2-year period was 2.20/100 PYs, which is in keeping with studies including clinical assessment rather than relying on health records alone. Extended follow-up of the TUDOR cohort with accrual of larger numbers of incident cases will allow risk factors for PsA to be explored in more depth., (Copyright © 2024 by the Journal of Rheumatology.)

Atopic dermatitis is one of the most common conditions managed in the community world-wide. Atopic dermatitis is under intense scrutiny by academic researchers, not to mention drug companies, enabling regular research in the area. Dermatologists have a growing appreciation of the complex causes of this common condition.

High salt intake may play a critical role in the etiology of psoriasis. Yet, evidence on the association of high salt intake with risk of psoriasis is limited. To estimate the association between frequency of adding salt to foods and risk of psoriasis. We conducted a prospective cohort study of 433,788 participants from the UK Biobank. Hazard ratios (HRs) and their 95 % confidence intervals (CIs) for risk of psoriasis in relation to frequency of adding salt to foods were estimated using multivariable Cox proportional hazards models. We further evaluated the joint association of adding salt to foods and genetic susceptibility with risk of psoriasis. We conducted a mediation analysis to assess how much of the effect of adding salt to foods on risk of psoriasis was mediated through several selected mediators. During a median of 14.0 years of follow-up, 4279 incident cases of psoriasis were identified. In the multivariable-adjusted model, a higher frequency of adding salt to foods was significantly associated with an increased risk of psoriasis ("always" versus "never/rarely" adding salt to foods, HR = 1.25, 95 % CI: 1.10, 1.41). The observed positive association was generally similar across subgroups. In the joint association analysis, we observed that participants with a high genetic risk (above the second tertile) and the highest frequency of adding salt to foods experienced 149 % higher risk of psoriasis, when compared with participants with a low genetic risk (below the first tertile) and the lowest frequency of adding salt to foods (HR = 2.49, 95 % CI: 2.05, 3.02). Mediation analysis revealed that 1.8 %–3.2 % of the positive association between frequency of adding salt and risk of psoriasis was statistically significantly mediated by obesity and inflammatory biomarkers such as C-reactive protein and systemic immune-inflammation index (all P values < 0.004). Our study demonstrated a positive association between frequency of adding salt to foods and risk of psoriasis. The positive association was independent of multiple other risk factors, and may be partially mediated through obesity and inflammation. • A higher frequency of adding salt to foods was related to an increased risk of psoriasis, regardless of other risk factors. • The frequency of adding salt to foods-psoriasis association may be partially mediated through obesity and inflammation. • Our findings provide evidence that greater salt intake may be a novel risk factor for psoriasis. [ABSTRACT FROM AUTHOR]

Introduction and aims Obesity is a chronic inflammatory state that is highly prevalent in people with psoriasis. There is evidence to suggest that increasing levels of adiposity promotes the risk of psoriasis development and worsens disease severity. The degree to which adiposity influences psoriasis varies between individuals, and it is also unclear which key genetic factors underpin this variation. Identifying this could be mechanistically informative in uncovering immunological pathways connecting adiposity and psoriasis. This project explores the hypothesis that the influence of adiposity on psoriasis has a genetic basis. Methods Firstly, we examined the comparative strength of association between a range of measures of adiposity and psoriasis in a population-based study (UK Biobank, n = 336 806). Secondly, we performed a genome-wide by environment interaction study (GWEIS) meta-analysis examining the interaction between key measures of adiposity and psoriasis susceptibility in two large population-based studies [UK Biobank and HUNT (n = 164 753)]. Thirdly, in view of this association between human leucocyte antigen (HLA)-C*06:02 and higher adiposity levels in psoriasis, we wanted to explore whether biological differences existed between HLA-stratified subgroups. To explore this, we performed HLA-C*06:02-stratified Mendelian randomization to establish whether a difference in causal effect of adiposity on psoriasis existed between subgroups. Results We found that measures of central obesity (including impedance and dual-energy x-ray absorptiometry/magnetic resonance imaging measures) were most strongly associated with both psoriasis risk and severity. A sexual dimorphism was observed, with a stronger effect in men compared with women. Through GWEIS meta-analysis, we found a significant interaction between HLA-C*06:02-status and waist circumference on psoriasis risk (P = 3.69e−08). No significant difference in causal effect of body mass index or waist circumference on psoriasis risk were found in HLA-C*06:02-stratified subgroups. Conclusions These findings underscore the significance of central adiposity in influencing psoriasis risk. This study also emphasizes both the value and limitations of HLA-C*06:02 as a potential biomarker for distinguishing metabolically-driven psoriasis. [ABSTRACT FROM AUTHOR]

Summary: Chronic plaque psoriasis is an inflammatory skin disease in which genetic predisposition along with environmental factors lead to the development of the disease, which affects 2% of the UK's population and is associated with extracutaneous morbidities and a reduced quality of life. A complex crosstalk between innate and adaptive immunity, the epithelia and the vasculature maintain the inflammatory milieu in psoriasis. Despite the development of promising treatment strategies, mostly targeting the immune system, treatments fail to fulfil every patient's goals. Vascular endothelial growth factor‐A (VEGF‐A) mediates angiogenesis and is upregulated in the plaques and plasma of patients with psoriasis. Transgenic expression of VEGF‐A in experimental models led to the development of skin lesions that share many psoriasis features. Targeting VEGF‐A in in vivo models of psoriasis‐like inflammation resulted in disease clearance. Anti‐angiogenesis treatments are widely used for cancer and eye disease and there are clinical reports of patients treated with VEGF‐A inhibitors who have experienced Psoriasis Area and Severity Index improvement. Existing psoriasis treatments downregulate VEGF‐A and angiogenesis as part of their therapeutic effect. Pharmacogenetics studies suggest the existence of different genetic signatures within patients with psoriasis that correspond with different treatment responsiveness and disease severity. There is a subset of patients with psoriasis with an increased predisposition to produce high levels of VEGF‐A, who may be most likely to benefit from anti‐VEGF‐A therapy, offering an opportunity to personalize treatment in psoriasis. Anti‐VEGF‐A therapies may offer an alternative to existing anticytokine strategies or be complementary to standard treatments for the management of psoriasis. [ABSTRACT FROM AUTHOR]

Background and Objective: Abrocitinib is a Janus kinase 1 inhibitor in development for the treatment of atopic dermatitis (AD). This work characterized orally administered abrocitinib population pharmacokinetics in healthy individuals, patients with psoriasis, and patients with AD and the effects of covariates on abrocitinib exposure. Methods: Abrocitinib concentration measurements (n = 6206) from 995 individuals from 11 clinical trials (seven phase I, two phase II, and two phase III) were analyzed, and a non-linear mixed-effects model was developed. Simulations of abrocitinib dose proportionality and steady-state accumulation of maximal plasma drug concentration (Cmax) and area under the curve (AUC) were conducted using the final model. Results: A two-compartment model with parallel zero- and first-order absorption, time-dependent bioavailability, and time- and dose-dependent clearance best described abrocitinib pharmacokinetics. Abrocitinib coadministration with rifampin resulted in lower exposure, whereas Asian/other race coadministration with fluconazole and fluvoxamine, inflammatory skin conditions (psoriasis/AD), and hepatic impairment resulted in higher exposure. After differences in body weight are accounted for, Asian participants demonstrated a 1.43- and 1.48-fold increase in Cmax and AUC, respectively. The overall distribution of exposures (Cmax and AUC) was similar in adolescents and adults after accounting for differences in total body weight. Conclusions: A population pharmacokinetics model was developed for abrocitinib that can be used to predict abrocitinib steady-state exposure in the presence of drug–drug interaction effects or intrinsic patient factors. Key covariates in the study population accounting for variability in abrocitinib exposures are Asian race and adolescent age, although these factors are not clinically meaningful. Clinical Trial Numbers: NCT01835197, NCT02163161, NCT02201524, NCT02780167, NCT03349060, NCT03575871, NCT03634345, NCT03637790, NCT03626415, NCT03386279, NCT03937258. Plain Language Summary: Abrocitinib is a drug approved in the UK and Japan for the treatment of atopic dermatitis. A population pharmacokinetic model for abrocitinib was developed based on data from 11 clinical trials that included 995 healthy individuals or patients with atopic dermatitis or psoriasis. Simulations of different patient factors, such as age, race, sex, body weight, liver function, and drug–drug interactions, were tested to examine differences in abrocitinib drug levels achieved in the body. The results of these simulations indicate that although there are some differences in abrocitinib exposure, no dose adjustments of abrocitinib are necessary based on these factors. [ABSTRACT FROM AUTHOR]

Psoriasis is a common chronic, systemic inflammatory disease, affecting approximately 2% of the population worldwide. Psoriasis is associated with profound psychosocial comorbidity with a burden that extends well beyond the physical signs and symptoms. Psychosocial comorbidities strongly associated with psoriasis include anxiety and depression, suicidal ideation, and substance misuse. There is a substantial unmet need for access to psychological support for people with skin disease in the UK. Recent reports found that while up to 98% of patients felt that their skin disease had affected their emotional or psychological well-being, only 18% sought help. This care gap is largely due to a lack of awareness about the limited available services alongside poor recognition, diagnosis, and triaging. Addressing psychosocial support needs starts with early identification, which can be complex and challenging. Once patients who need further support are identified, outcomes can be improved through prompt and effective treatment of inflammation, cognitive behavioural therapy, meditation and mindfulness-based therapy (including motivational interviewing), and to some extent psychotropic medication. Finally, resources for mental health support are notoriously limited, with dire consequences for patients. It is imperative that a proportion of the new funding promised for mental health services is bookmarked for dermatology patients and adequate provision of multidisciplinary psychodermatology teams to best serve the needs of this population. Ultimately, psoriasis is a complex condition with multifactorial psychological and biological drivers. Psoriasis is associated with high levels of distress, which is often under-recognized. Fully addressing this condition requires a holistic approach to the physical and psychosocial aspects to maximise adherence, efficacy, and optimise patient quality of life. [ABSTRACT FROM AUTHOR]

Summary: Background: In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults. Objectives: To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis. Methods: A case–control diagnostic accuracy study in 12 UK dermatology departments (2017–2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist‐diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping. Results: The sensitivity of the consensus‐agreed criteria and consensus scoring algorithm was 84·6%, the specificity was 65·1% and the area under the curve (AUC) was 0·75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well‐demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well‐demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76·8%, with specificity 72·7% and AUC 0·84. The c‐statistic optimism‐adjusted shrinkage factor was 0·012. Conclusions: This study provides examination‐ and history‐based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary‐care patients. External validation is now needed. [ABSTRACT FROM AUTHOR]

Although a peak incidence of psoriasis in women aged around 60 years has been observed, the link between reproductive lifespan and late-onset psoriatic diseases is underexplored. This study aims to elucidate the association between reproductive lifespan and the risk of late-onset psoriasis and psoriatic arthritis (PsA). Utilizing the UK Biobank data, we conducted a prospective cohort study in postmenopausal women without baseline psoriatic diseases. The exposure variables included age at natural menopause (ANM) and duration from menarche to menopause, termed reproductive years. The outcome variables were incident psoriasis and PsA. We employed Cox regression analysis, factoring in polygenic risk scores for psoriatic diseases and recognized risk factors. We found that later ANM and longer reproductive years were significantly associated with decreased risks of late-onset psoriasis and PsA in a dose-dependent manner (P<.05). ANM after age 55 years led to a 34 and 46% risk reduction in late-onset psoriasis and PsA, respectively, compared with ANM before age 45 years (P<.001). The population-attributable risks of ANM were 17.4% for late-onset psoriasis and 21.6% for PsA. In conclusion, reproductive lifespan, with its inherent homeostasis, plays a pivotal yet overlooked role in late-onset psoriatic diseases. Investigations into estrogen-centric causes and sex-specific interventions are imperative., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Summary: Background: New technologies have enabled the potential for stratified medicine in psoriasis. It is important to understand patients' preferences to enable the informed introduction of stratified medicine, which is likely to involve a number of individual tests that could be collated into a prescribing algorithm for biological drug selection to be used in clinical practice. Objectives: To quantify patient preferences for an algorithm‐based approach to prescribing biologics ('biologic calculator') in psoriasis. Methods: An online survey comprising a discrete choice experiment (DCE) was conducted to elicit the preferences of two purposive samples of adults living with psoriasis in the UK, identified from a psoriasis patient organization (Psoriasis Association) and an online panel provider (Dynata). Respondents chose between two biologic calculators and conventional prescribing described using five attributes: treatment delay; positive predictive value; negative predictive value; risk of infection; and cost saving to the National Health Service. Each participant selected their preferred alternative from six hypothetical choice sets. Additional data, including sociodemographic characteristics, were collected. Choice data were analysed using conditional logit and fully correlated random parameters logit models. Results: Data from 212 respondents (67 from the Psoriasis Association and 145 from Dynata) were analysed. The signs of all estimated coefficients were consistent with a priori expectations. Respondents had a strong preference for a high predictive accuracy and avoiding serious infection, but there was evidence of systematic differences in preferences between the samples. Conclusions: This study indicates that individuals with psoriasis would value a biologic calculator and suggested that such a biologic calculator should have sufficient accuracy to predict future response and risk of serious infection from the biologic. What is already known about the topic? Factors such as patient characteristics, location of psoriasis and genetics have been found to affect response to targeted biological therapy in people with psoriasis.The knowledge of such factors paves the way for algorithm‐based prescribing (stratified medicine). What does this study add? We investigated patient preferences for a hypothetical example of algorithm‐based prescribing of biologics for psoriasis vs. the conventional approach to prescribing.The strongest predictors of patient preferences for stratified medicine were the ability to predict nonresponse to a biologic, the ability to predict a positive response and the risk of avoiding a serious infection from the biologic. What are the clinical implications of this work? This study suggests that clinical tools to enable the implementation of stratified medicine in psoriasis should be designed with the goal of reaching a sufficient level of predictive accuracy and predicting the risk of serious infection given the cost of implementing these into clinical practice. Linked Comment: J.M. Gonzalez et al. Br J Dermatol 2021; 185:882–883. Plain language summary available online [ABSTRACT FROM AUTHOR]

Background: There is limited guidance on which biologic therapies should be prioritised for the treatment of moderate-to-severe psoriasis, amongst the many available options. New mode-of-action biologics, as well as recently available biosimilars for existing biologics, continue to be developed making the choice of treatment sequence increasingly complex. Objectives: The aim of this analysis was to develop a cost-effectiveness model to determine the optimal placement of biologic therapies on the treatment pathway for psoriasis in the UK. Methods: A cohort-based Markov model was developed in Microsoft Excel, from the perspective of the National Health Service and Personal and Social Services in the UK. The model followed a hypothetical cohort of patients over a lifetime. The health states in the model were defined by Psoriasis Area and Severity Index response. In the model, patients could receive a total of four separate treatments, including three active interventions and best supportive care. Results: A fully incremental analysis was undertaken on a subset of commonly used treatment sequences. The results of the list price analyses determined the most cost-effective sequence to be adalimumab biosimilar followed by ustekinumab, secukinumab, then best supportive care. This sequence is associated with total costs of £78,731 and total quality-adjusted life-years of 14.74 over a patient's lifetime. Conclusions: This research suggests that the optimal first-line treatment in the UK is adalimumab biosimilar. The optimal second-line and third-line treatments depend on the magnitude of confidential discounts applied to the biologic treatments. [ABSTRACT FROM AUTHOR]

Introduction: In the UK, biologic interventions for plaque psoriasis can either be administered in a hospital setting or following delivery to a patient's home. To date, limited research has been undertaken on how the administration route affects the overall treatment costs and the implications for this on UK clinical practice. The objective was to explore the cost implications of different administration routes for plaque psoriasis biologic interventions in the UK. Methods: A simple economic model was developed to estimate and compare the total cost of drug administration over 2 years for all biologic interventions that have been approved by the National Institute of Health and Care Excellence for use in patients with moderate-to-severe plaque psoriasis. Administration costs were estimated for two different scenarios: administration in a hospital setting or following home delivery [paid for by the National Health Service (NHS)]. Results: Costs of home delivery and administration in hospital over a 2-year time horizon varied substantially based on the choice of intervention. For home delivery, the lowest cost of £693 occurred with risankizumab, tildrakizumab and ustekinumab, while the highest cost of £3445 occurred with adalimumab, brodalumab, certolizumab and etanercept. For the scenario in which the interventions were administered in a hospital setting the costs ranged from £4224 for ustekinumab to £7463 for brodalumab. Conclusion: These results indicate that drug administration costs are meaningful and should be given greater consideration in the selection process of treatments for plaque psoriasis. Additionally, the NHS could save money by paying for drugs to be delivered to a patient's home, rather than administering them in a hospital setting. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Background: Psoriasis impacts the health and psychosocial functioning of patients, conferring a significant economic burden on healthcare systems. There remain unmet needs in psoriasis care, which if addressed by research, could improve clinical outcomes. Aim: To research priorities and identify a health service delivery model from the UK Psoriasis Priority Setting Partnership (PsPSP). Methods: Between July 2017 and November 2018, we invited people with lived experience of psoriasis and healthcare professionals to (i) identify unmet needs, and (ii) prioritize the order in which these should be addressed by research. We collaborated with the Psoriasis Association and used methodology established by the James Lind Alliance, which pioneers the joint setting of research priorities by patients and clinicians worldwide. Results: In our initial harvesting survey (Survey 1), 2133 questions were submitted by 805 individuals. Submissions that had not been answered by research (true uncertainties) were supplemented with evidence gaps from systematic reviews/guidelines published in the previous 5 years and refined to produce 55 indicative questions. Voting in Survey 2, by 1154 individuals, enabled a shortlist of questions, which were prioritized during the final workshop to produce a top 20 list of research questions. Submissions on health service delivery (5.8% of the total submissions), which were analysed separately, described a blueprint for psoriasis care. Conclusions: The PsPSP will inform the translational research agenda, ensuring that future research is relevant for the needs of people with psoriasis and those who manage the disease. Submissions on health service delivery describe a model of holistic, patient‐focused care providing high‐quality, effective management for patients with psoriasis. [ABSTRACT FROM AUTHOR]

Summary: Background: Psoriasis is associated with risk factors for serious infections, but the independent relationship between psoriasis and serious infection is as yet unclear. Objectives: To determine whether people with psoriasis have a higher risk of hospitalization due to any infection, respiratory infections, soft‐tissue and skin infections, or a higher risk of death due to infection. Methods: We conducted a cohort study of people (≥ 18 years) with psoriasis using the UK Clinical Practice Research Datalink (CPRD GOLD) linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records between 1 April 2003 and 31 December 2016, and matched with up to six comparators on age, sex and general practice. Hospitalization was ascertained from HES records; death was ascertained from ONS mortality records. Stratified Cox proportional hazard models were estimated, with stepwise adjustment in different models for potential confounders or mediators between psoriasis and serious infection. Results: There were 69 315 people with psoriasis and 338 620 comparators who were followed up for a median (interquartile range) of 4·9 (5·9) and 5·1 (6·3) years, respectively. People with psoriasis had a higher incidence rate of serious infection [20·5 per 1000 person‐years, 95% confidence interval (CI) 20·0–21·0, n = 7631] compared with those without psoriasis (16·1 per 1000 person‐years, 95% CI 15·9–16·3, n = 30 761). The fully adjusted hazard ratio for the association between psoriasis and serious infection was 1·36 (95% CI 1·31–1·40), with similar results across the other outcomes. Conclusions: Psoriasis is associated with a small increase in the risk of serious infection. Further research is needed to understand how psoriasis predisposes to a higher risk of infection. What is already known about this topic? Several studies have shown that people with psoriasis have a higher risk of hospitalization due to infection, but these studies are limited by residual confounding for lifestyle factors or underestimation of the true incidence of hospital admissions from primary care electronic health records. What does this study add? Using a large primary care database linked with secondary care Hospital Episode Statistics, we found that, after adjusting for potential confounders and mediators, the hazard ratio for the association between psoriasis and the development of serious infection was 1·36 (95% confidence interval 1·31–1·40).In summary, we show that having psoriasis is independently associated with a small but increased risk of serious infection. Linked Comment:Naldi. Br J Dermatol 2021; 184:6. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Psoriasis remains one of the commonest conditions seen in dermatological practice, and its treatment is one of the greatest cost burdens for the UK National Health Service. Treatment of psoriasis is complex, with numerous overlapping lines and therapies used in combination. This complexity reflects the underlying pathophysiology of the disease as well as the heterogeneous population that it affects. National Institute for Health and Care Excellence (NICE) guidance for the treatment of psoriasis has been available since 2013, and has been the subject of three national audits conducted by the British Association of Dermatologists. This report synthesizes the results of the most recent of those exercises and places it in the context of the NICE guidance and previous audits. It clearly shows the significant burden of disease, issues with provision of services and long waiting times and the marked shift in therapies towards targeted biologic therapies. [ABSTRACT FROM AUTHOR]

Summary: Background: Stress is commonly cited as a risk factor for psoriasis and atopic eczema, but such evidence is limited. Objectives: To investigate the association between partner bereavement (an extreme life stressor) and psoriasis or atopic eczema. Methods: We conducted cohort studies using data from the U.K. Clinical Practice Research Datalink (1997–2017) and Danish nationwide registries (1997–2016). The exposed cohort was partners who experienced partner bereavement. The comparison cohort was up to 10 nonbereaved partners, matched to each bereaved partner by age, sex, county of residence (Denmark) and general practice (U.K.). Outcomes were the first recorded diagnosis of psoriasis or atopic eczema. We estimated hazard ratios (HRs) and confidence intervals (CIs) using a stratified Cox proportional hazards model in both settings, which were then pooled in a meta‐analysis. Results: The pooled adjusted HR for the association between bereavement and psoriasis was 1·01 (95% CI 0·98–1·04) across the entire follow‐up. Similar results were found in other shorter follow‐up periods. Pooled adjusted HRs for the association between bereavement and atopic eczema were 0·97 (95% CI 0·84–1·12) across the entire follow‐up, 1·09 (95% CI 0·86–1·38) within 0–30 days, 1·18 (95% CI 1·04–1·35) within 0–90 days, 1·14 (95% CI 1·06–1·22) within 0–365 days and 1·07 (95% CI 1·02–1·12) within 0–1095 days. Conclusions: We found a modest increase in the risk of atopic eczema within 3 years following bereavement, which peaked in the first 3 months. Acute stress may play a role in triggering onset of new atopic eczema or relapse of atopic eczema previously in remission. We observed no evidence for increased long‐term risk of psoriasis and atopic eczema following bereavement. What's already known about this topic? Psychological stress is commonly cited as a risk factor for psoriasis and atopic eczema. However, clinical evidence supporting such associations is limited.Current epidemiological evidence for the relationship is limited by small sample sizes and difficulty measuring stress. What does this study add? In two population‐based cohort studies, there was no evidence of an increased risk of psoriasis associated with partner bereavement.There was a short‐term increased risk of atopic eczema in the 3 years following partner bereavement, which peaked during the first year. However, there was no evidence of an increased long‐term risk of atopic eczema.Acute stress may trigger onset or relapse of atopic eczema, leading to an increased risk of atopic eczema in the short term following partner bereavement. Linked Comment: von Kobyletzki. Br J Dermatol 2020; 183:207. Plain language summary available online [ABSTRACT FROM AUTHOR]

Psoriasis can adversely affect quality of life (QoL) and emotional well-being. In this UK prospective observational study we evaluated the 'real-world' impact of adalimumab on QoL and the physical/psychological effects of moderate-to-severe psoriasis. Hundred and forty-three biologic-naïve patients with moderate-to-severe psoriasis, receiving adalimumab in clinical practice, were included. Patients completed a series of questionnaires at baseline (adalimumab initiation), 4 and 16-weeks and 6-months post-adalimumab initiation during routine visits. The main outcome measure was the proportion of Dermatology Life Quality Index (DLQI) 'responders' at 16 weeks, defined as ≥5 point reduction from baseline or DLQI = 0.90% (95% CI = 80.8%–94.6%) of evaluable patients were DLQI responders at 16-weeks. There were significant improvements at 16 weeks in patient-reported measures of QoL, mental and physical well-being, cutaneous body image, anxiety, depression and psoriasis severity, which were maintained at 6-months. Adalimumab treatment was associated with improvements in patients' QoL and psychological functioning, which occurred contemporaneously with improvements in cutaneous disease. [ABSTRACT FROM AUTHOR]

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real‐world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first‐line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti‐drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one‐compartment model. A maximum effect (Emax) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half‐maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Objectives To determine the independent association of central adiposity, assessed by waist circumference, with odds of psoriasis, PsA and RA prevalence after controlling for general adiposity (BMI). Methods A cross-sectional study of UK Biobank participants aged 40–70 years was performed. Logistic regression was used to calculate the odds of psoriasis, PsA and RA occurrence compared with controls without these conditions by waist circumference, adjusting for covariates: age, sex, smoking status, socioeconomic deprivation and self-reported physical activity (Model 1), followed additionally by BMI (Model 2). Results A total of 502 417 participants were included; 5074 with psoriasis (1.02%), 905 with PsA (0.18%), 5532 with RA (1.11%) and 490 906 controls without these conditions. Adjusted odds ratios (ORs) (Model 1) for psoriasis, PsA and RA, per s. d. (13.5 cm) higher waist circumference were 1.20 (95% CI 1.16, 1.23), 1.30 (95% CI 1.21, 1.39) and 1.21 (95% CI 1.17, 1.24), respectively (all P < 0.001). These ORs remained significant after further adjustment for BMI (Model 2) in psoriasis [OR 1.19 (95% CI 1.12, 1.27), P < 0.001] and RA [OR 1.19 (95% CI 1.12, 1.26), P < 0.001], but not in PsA [OR 1.11 (95% CI 0.95, 1.29), P = 0.127]. Conclusion Central adiposity as measured by waist circumference is associated with greater odds of psoriasis and RA prevalence after adjustment for confounders and for BMI. Our findings add support for central adiposity as a long-term clinically relevant component of these conditions. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence regarding biologics dosing patterns and its costs among psoriasis patients in the United Kingdom (UK). Objective: This retrospective study assessed biologics dose increase beyond labelled dose and associated UK pharmacy costs in moderate to severe psoriasis patients. Methods: Adult psoriasis patients on biologic prescription for ≥12 continuous months between January 2010 and March 2015 with their diagnosis recorded in the UK Hospital Treatment Insights Database within one month of such prescription were included. The proportion of patients receiving ≥30% higher the average daily maintenance dose as per the UK product label, and associated 12-month costs were reported. Results: The study included 362 patients, receiving adalimumab (48%), etanercept (17%), ustekinumab (12%), and infliximab (23%). Beyond labelled dose increase was noted in 14% adalimumab, 20% etanercept, 18% ustekinumab and 28% infliximab patients with an associated mean annual extra cost per patient of £7936, £5912, £2422 and £2275, respectively. Conclusion: Dose increase beyond labelled dose of biologics was commonly observed in moderate to severe psoriasis in the UK and resulted in substantial annual incremental pharmacy costs. [ABSTRACT FROM AUTHOR]

Summary: Background: Patients with psoriasis are often concerned about the risk of serious infection associated with systemic psoriasis treatments. Objectives: To develop and externally validate a prediction model for serious infection in patients with psoriasis within 1 year of starting systemic therapies. Methods: The risk prediction model was developed using the British Association of Dermatologists Biologic Interventions Register (BADBIR), and the German Psoriasis Registry PsoBest was used as the validation dataset. Model discrimination and calibration were assessed internally and externally using the C‐statistic, the calibration slope and the calibration in the large. Results: Overall 175 (1·7%) out of 10 033 participants from BADBIR and 41 (1·7%) out of 2423 participants from PsoBest developed a serious infection within 1 year of therapy initiation. Selected predictors in a multiple logistic regression model included nine baseline covariates, and starting infliximab was the strongest predictor. Evaluation of model performance showed a bootstrap optimism‐corrected C‐statistic of 0·64 [95% confidence interval (CI) 0·60–0·69], calibration in the large of 0·02 (95% CI −0·14 to 0·17) and a calibration slope of 0·88 (95% CI 0·70–1·07), while external validation performance was poor, with C‐statistic 0·52 (95% CI 0·42–0·62), calibration in the large 0·06 (95% CI −0·25 to 0·37) and calibration slope 0·36 (95% CI −0·24 to 0·97). Conclusions: We present the first results of the development of a multivariable prediction model. This model may help patients and dermatologists in the U.K. and the Republic of Ireland to identify modifiable risk factors and inform therapy choice in a shared decision‐making process. What's already known about this topic? Patients and their clinicians are often concerned about the risk of serious infection associated with biological therapies for the treatment of psoriasis.However, there are no current tools available to estimate an individual's risk of serious infection when starting a systemic therapy. What does this study add? This study found that the serious infection risk prediction model had good calibration and moderate discriminationThe model included chronic obstructive pulmonary disease, alcohol intake, number of comorbidities and employment status, in addition to age, sex, Psoriasis Area and Severity Index, choice of starting therapy and body mass index.These are the first results of the multivariable prediction model, which may help patients and dermatologists in the U.K. and the Republic of Ireland to identify modifiable risk factors and inform therapy choice in a shared decision‐making process. Respond to this article Plain language summary available online [ABSTRACT FROM AUTHOR]