Implementing well-being in the management of psoriasis: An expert recommendation.

Psoriasis causes detriment in a person's physical, mental and social health which impairs their quality of life (QoL). However, the current psoriasis management may not adequately address all relevant health domains. Since the goal of healthcare is to restore or maintain health, health outcomes should include all areas of the patient's overall health. Life satisfaction, QoL and patient well-being are essential to a comprehensive approach to the disease. With the inclusion of more people-centred policies, care of patients with psoriasis should evolve towards a holistic and integrated assessment of the disease impact, including subjective measures of well-being in order to encompass all aspects of health. The main objective of this expert review is to give the concept of well-being a place as an entity within the holistic therapeutic approach for patients with psoriasis. Identifying and defining common goals beyond the skin with the patient and testing them throughout the course of treatment will benefit and enhance treatment success. We propose a series of recommendations for application in clinical practice, providing tangible clinical guidance for implementing well-being in the management of psoriasis. Among the recommendations are the need to initially listen to the patient, to know their level of empowerment or what they want to achieve, their preferences in decision making, the evaluation of not only the physical but also the emotional impact of the disease (well-being), the definition of the aspects that can generate a cumulative deterioration of the disease throughout life, and a continuous assessment of the patient's preferences with the opinion of the expert clinician and the integration of the knowledge of external clinical evidence.

Risk of serious infection and infection mortality in patients with psoriasis: A nationwide cohort study using the Taiwan National Health Insurance claims database.

BACKGROUND: The risks of serious infections that lead to hospitalization and mortality in patients with psoriasis in Asia have not been comprehensively studied. OBJECTIVES: We examined the incidence of serious infection and infection mortality in patients with psoriasis. METHODS: This population-based retrospective cohort study used the Taiwan National Health Insurance claims database from 2000 to 2017. Adult patients with psoriasis were identified by a relevant International Classification of Diseases (ICD) code and matched to six comparators without psoriasis on age and sex. Psoriasis patients were categorized as having moderate-to-severe disease once exposed to systemic therapies, phototherapy or biologic therapies. The incidence of serious infection and infection mortality were identified by ICD codes from inpatient hospitalization and death registration. Cox proportional hazard models were used to compare the risk, and the results were adjusted for covariates and presented as adjusted hazard ratios (aHR) and 95% confidence interval (95% CI). RESULTS: Overall, 185,434 psoriasis patients and 1,112,581 comparators were included. A higher rate of serious infection (aHR: 1.21, 95% CI: 1.19-1.22) was found in patients with psoriasis compared to matched comparators without psoriasis, and the risk was enhanced when patients had moderate-to-severe psoriasis (aHR: 1.30, 95% CI: 1.27-1.34). Specifically, there was an increased risk of serious infection due to respiratory infections (aHR: 1.11, 95% CI: 1.09-1.13), skin/soft-tissue infections (aHR: 1.57, 95% CI: 1.52-1.62), sepsis (aHR: 1.23, 95% CI: 1.19-1.27), urinary tract infections (aHR: 1.11, 95% CI: 1.08-1.14), hepatitis B (aHR: 1.18, 95% CI: 1.06-1.30) and hepatitis C (aHR: 1.49, 95% CI: 1.32-1.69). Furthermore, psoriasis patients were associated with a higher risk of infection-related mortality (aHR: 1.15, 95% CI: 1.11-1.18) compared to matched comparators. CONCLUSION: Patients with psoriasis had a higher risk of serious infection and infection mortality, which was enhanced by moderate-to-severe psoriasis. Practitioners should be aware of the increased risk in patients with psoriasis, but it should not be a barrier to offering effective treatment.

Real-World Experience of Patient-Relevant Benefits and Treatment Satisfaction with Apremilast in Patients with Psoriasis: An Analysis of the APPRECIATE Study.

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

Efficacy of ixekizumab in patients with moderate-to-severe plaque psoriasis and prediabetes or type 2 diabetes.

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

Enhanced NF-κB signaling in type-2 dendritic cells at baseline predicts non-response to adalimumab in psoriasis.

Biologic therapies have transformed the management of psoriasis, but clinical outcome is variable leaving an unmet clinical need for predictive biomarkers of response. Here we perform in-depth immunomonitoring of blood immune cells of 67 patients with psoriasis, before and during therapy with the anti-TNF drug adalimumab, to identify immune mediators of clinical response and evaluate their predictive value. Enhanced NF-κBp65 phosphorylation, induced by TNF and LPS in type-2 dendritic cells (DC) before therapy, significantly correlates with lack of clinical response after 12 weeks of treatment. The heightened NF-κB activation is linked to increased DC maturation in vitro and frequency of IL-17+ T cells in the blood of non-responders before therapy. Moreover, lesional skin of non-responders contains higher numbers of dermal DC expressing the maturation marker CD83 and producing IL-23, and increased numbers of IL-17+ T cells. Finally, we identify and clinically validate LPS-induced NF-κBp65 phosphorylation before therapy as a predictive biomarker of non-response to adalimumab, with 100% sensitivity and 90.1% specificity in an independent cohort. Our study uncovers important molecular and cellular mediators underpinning adalimumab mechanisms of action in psoriasis and we propose a blood biomarker for predicting clinical outcome.

Psoriasis and Treatment: Past, Present and Future Aspects.

The management of psoriasis has evolved considerably over the past 100 years. This has occurred in parallel with our understanding of the pathogenesis of this common, complex and enigmatic disease. It should be celebrated as an outstanding example of successful translational research. With precise targeting of immune pathways for the treatment of psoriasis with new biologics and small molecules has come the realisation that the most effective approach to patient management is a holistic one which encompasses the biopsychosocial nature of the disease. This involves a stratified medicine approach to identifying the best drug for an individual allied to patient education, screening for comorbidity, and regular review as both the clinical presentation and the patient's needs will change over time. Al-though there is not yet a cure for psoriasis - the whole person, systems approach to patient management, that is in part dependent on early intervention, should help to ensure an optimal outcome.

A Framework for Multi-Omic Prediction of Treatment Response to Biologic Therapy for Psoriasis.

Biologic therapies have shown high efficacy in psoriasis, but individual response varies and is poorly understood. To inform biomarker discovery in the Psoriasis Stratification to Optimise Relevant Therapy (i.e., PSORT) study, we evaluated a comprehensive array of omics platforms across three time points and multiple tissues in a pilot investigation of 10 patients with severe psoriasis, treated with the tumor necrosis factor (TNF) inhibitor, etanercept. We used RNA sequencing to analyze mRNA and small RNA transcriptome in blood, lesional and nonlesional skin, and the SOMAscan platform to investigate the serum proteome. Using an integrative systems biology approach, we identified signals of treatment response in genes and pathways associated with TNF signaling, psoriasis pathology, and the major histocompatibility complex region. We found association between clinical response and TNF-regulated genes in blood and skin. Using a combination of differential expression testing, upstream regulator analysis, clustering techniques, and predictive modeling, we show that baseline samples are indicative of patient response to biologic therapies, including signals in blood, which have traditionally been considered unreliable for inference in dermatology. In conclusion, our pilot study provides both an analytical framework and empirical basis to estimate power for larger studies, specifically the ongoing PSORT study, which we show as powered for biomarker discovery and patient stratification.

HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis.

BACKGROUND: Biologic therapies can be highly effective for the treatment of severe psoriasis, but response for individual patients can vary according to drug. Predictive biomarkers to guide treatment selection could improve patient outcomes and treatment cost-effectiveness. OBJECTIVE: We sought to test whether HLA-C*06:02, the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the 2 most commonly prescribed biologics for psoriasis: adalimumab (anti-TNF-α) and ustekinumab (anti-IL-12/23). METHODS: This study uses a national psoriasis registry that includes longitudinal treatment and response observations and detailed clinical data. HLA alleles were imputed from genome-wide genotype data for 1326 patients for whom 90% reduction in Psoriasis Area and Severity Index score (PASI90) response status was observed after 3, 6, or 12 months of treatment. We developed regression models of PASI90 response, examining the interaction between HLA-C*06:02 and drug type (adalimumab or ustekinumab) while accounting for potentially confounding clinical variables. RESULTS: HLA-C*06:02-negative patients were significantly more likely to respond to adalimumab than ustekinumab at all time points (most strongly at 6 months: odds ratio [OR], 2.95; P = 5.85 × 10-7), and the difference was greater in HLA-C*06:02-negative patients with psoriatic arthritis (OR, 5.98; P = 6.89 × 10-5). Biologic-naive patients who were HLA-C*06:02 positive and psoriatic arthritis negative demonstrated significantly poorer response to adalimumab at 12 months (OR, 0.31; P = 3.42 × 10-4). Results from HLA-wide analyses were consistent with HLA-C*06:02 itself being the primary effect allele. We found no evidence for genetic interaction between HLA-C*06:02 and ERAP1. CONCLUSION: This large observational study suggests that reference to HLA-C*06:02 status could offer substantial clinical benefit when selecting treatments for severe psoriasis.

Risk of Serious Infection in Patients with Psoriasis Receiving Biologic Therapies: A Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Serious infection is a concern for patients with psoriasis receiving biologic therapies. We assessed the risk of serious infections for biologics used to treat psoriasis by comparison with a cohort receiving non-biologic systemic therapies in a propensity score-weighted Cox proportional hazards model using data from the British Association of Dermatologists Biologic Interventions Register. Overall, 1,352; 3,271; and 994 participants were included in the etanercept, adalimumab, ustekinumab cohorts, respectively, and 3,421 participants were in the non-biologic cohort. A total of 283 patients had a serious infection; the incidence rates with 95% confidence intervals (CI) per 1,000 person-years were as follows: non-biologic, 14.2 (11.5-17.4); etanercept, 15.3 (11.6-20.1); adalimumab, 13.9 (11.4-16.6); and ustekinumab, 15.1 (10.8-21.1). No significant increases in the risk of serious infection were observed for etanercept (hazard ratio [HR] = 1.10, 95% CI = 0.75-1.60), adalimumab (HR = 0.93, 95% CI = 0.69-1.26), or ustekinumab (HR = 0.92, 95% CI = 0.60-1.41) compared with non-biologic systemic therapies or methotrexate-only (etanercept: HR = 1.47, 95% CI = 0.95-2.28; adalimumab: HR = 1.26, 95% CI = 0.86-1.84; ustekinumab: HR = 1.22, 95% CI = 0.75-1.99). The risk of serious infection should not be a key discriminator for patients and clinicians when choosing between non-biologic systemic therapies, etanercept, adalimumab, and ustekinumab for the treatment of psoriasis.

The challenges of assessing patients' medication beliefs: a qualitative study.

BACKGROUND: An estimated 50% of patients do not take their medication as prescribed, with medication adherence associated with adverse outcomes and higher costs of care. The Necessity-Concerns Framework identified individual's beliefs about their medication as playing a key role in adherence, and UK Clinical Adherence Guidelines recommend eliciting and incorporating individual's perceptions of their medication within the consultation. The Beliefs about Medicines Questionnaire (BMQ) is widely used to assess medication beliefs, however, given the condition-specific nature of some self-management regimens, it is unknown whether this tool is able to fully capture beliefs about more complex medication regimens. METHODS: We examined the challenges of assessing medication beliefs using the BMQ in 20 people with a complex relapsing-remitting condition recruited from community sources. Data were collected from people with psoriasis; a patient group characterised by complex medication regimens, which include therapies that are applied topically, phototherapy/photochemotherapy, and therapies that are administered orally or via subcutaneous or intravenous injections. Semi-structured cognitive interviews were undertaken, with responses coded using established schedules and analysed using Content analysis. RESULTS: Individual's beliefs about their condition specific therapies were not accurately captured by the BMQ. Medication beliefs as expressed during 'real-time' completion of the BMQ were underestimated, or failed to be captured, by the corresponding scores given by participants. There was mismatch between the terminology used in the scale and individuals perceptions of their condition and the complexity of its management and treatment outcomes. Currently the BMQ cannot represent beliefs about medicines underuse, even though some individuals with psoriasis viewed access to therapies as overly restrictive. Some the BMQ items were misinterpreted in part due to ambiguous item wording or due to misreading by participants. CONCLUSIONS: This is the first study to identify general and condition-specific difficulties experienced by individuals completing the BMQ in 'real time'. The main implication of this research is the need to develop condition-specific versions of the BMQ in order that this important instrument can capture the full range of medication beliefs in individuals living with a complex relapsing-remitting condition. Access to condition-specific versions could significantly increase our understanding of beliefs which facilitate or reduce medication adherence.

Risk of Serious Infections in Patients with Psoriasis on Biologic Therapies: A Systematic Review and Meta-Analysis.

A comprehensive evaluation of the risk of serious infections in biologic therapies for psoriasis is lacking. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies reporting serious infections in people taking any licensed biologic therapy for psoriasis compared with those taking placebo, nonbiologic therapy, or other biologic therapies. The quality of the studies was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. No significant heterogeneity was detected in data from 32 RCTs (n = 13,359 participants) and one cohort study (n = 4,993 participants). In adults, low- to very-low-quality RCT data showed no significant difference between any biologic therapy and placebo at weeks 12-16 (overall pooled Peto odds ratio = 0.71, 95% confidence interval = 0.36-1.41) and weeks 20-30 (odds ratio = 2.27, 95% confidence interval = 0.45-11.49). No significant differences were found in any of the other comparisons in underpowered RCT data. Prospective cohort study data of low quality suggests that only adalimumab (adjusted hazard ratio [adjHR] = 2.52, 95% confidence interval = 1.47-4.32) was associated with a significantly higher risk of serious infection compared with retinoid and/or phototherapy in adults. No association between biologic therapies and serious infections in patients with psoriasis who were eligible for RCTs was detected. Further observational studies are needed to inform the uncertainty around this risk in the real world.

Effectiveness of Subcutaneous Methotrexate in Chronic Plaque Psoriasis.

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

The role of personal models in clinical management: Exploring health care providers' beliefs about psoriasis.

OBJECTIVES: Individuals' illness representations, including beliefs about psoriasis (a complex immune-mediated condition), and their emotional responses to the condition guide self-management behaviour. It is also plausible that health care providers' illness representations guide their own management of psoriasis. Patients commonly report poor health care experiences related to psoriasis, and the role of health care providers' beliefs, emotions, as well as their knowledge, experiences and behaviours ('personal models') in this is unexplored. This study aimed explore health care providers' personal models of psoriasis. DESIGN AND METHODS: Qualitative analysis of 23 semi-structured interviews with health care professionals providing care for psoriasis patients was performed. Purposive sampling achieved maximum variation regarding participant discipline, level of experience, gender and age. The self-regulatory/common sense model informed data collection and initial data analysis. Principles of framework analysis were used to generate predetermined and emergent key issues related to practitioners' personal models. RESULTS: Three types of personal model emerged. Sophisticated-Linear Model: 70% of practitioners recognized psoriasis as a complex condition but managed it as a skin condition. Mixed Model: 17% of practitioners recognized/managed some elements of psoriasis as complex and some as a skin condition. Sophisticated-Sophisticated Model: 13% recognized and managed psoriasis as a complex condition. Across the data set, five themes emerged illustrating key patterns underpinning these different models including (1) Recognising complexity, (2) Putting skin first, (3) Taking on the complexities of psoriasis with the patient, (4) Aiming for clearance, and (5) Affective experiences within psoriasis consultations. CONCLUSIONS: Health care providers recognized psoriasis as a complex condition but commonly reported managing psoriasis as a simple skin condition. Providers' beliefs and management approaches varied in the extent to which they were consistent with one another; and their emotional experiences during consultations may vary depending upon their personal model. Findings could inform future dermatology training programmes by highlighting the role of health care providers' illness representations in clinical management of the condition. STATEMENT OF CONTRIBUTION: What is already known on this subject? Health behaviour is predicted by underlying beliefs and emotions associated with an illness and its treatment. Few studies have examined health care providers' beliefs and emotions about the illnesses they manage in clinical practice. Many patients are dissatisfied with dermatology consultations and wish to be treated holistically. What does this study add? Qualitative exploration of health care providers' beliefs/emotions revealed their personal models of psoriasis. Providers' personal models of psoriasis vary in coherence and are often skin rather than whole person focused. Further investigation of health care providers' models of psoriasis and their impact on health outcomes is needed.

Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Drug survival reflects a drug's effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09-1.37), being a current smoker (HR 1.19; 95% CI: 1.03-1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00-1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71-0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45-1.84) or infliximab (HR 1.56; 95% CI: 1.16-2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37-0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients.

Psoriasis: the future.

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

The Simplified Psoriasis Index (SPI): a practical tool for assessing psoriasis.

The Simplified Psoriasis Index (SPI) is a summary measure of psoriasis with separate components for current severity (SPI-s), psychosocial impact (SPI-p), and past history and interventions (SPI-i). It derives from the Salford Psoriasis Index but replaces Psoriasis Area and Severity Index (PASI) with a composite weighted severity score designed to reflect the impact of psoriasis affecting functionally or psychosocially important body sites. Two complementary versions are available, differing only in that current severity (SPI-s) is either professionally (proSPI-s) or patient self-assessed (saSPI-s). This study examined the criterion and construct validity and response distribution of proSPI-s, saSPI-s, and SPI-p in 100 patients with plaque psoriasis. A further 50 patients were assessed for test-retest reliability of these three components. Interrater reliability of proSPI-s was assessed in 12 patients, each assessed by 12 assessors (144 assessments). There was close correlation between PASI and proSPI-s (r=0.91); SPI-p was closely correlated with the Dermatology Life Quality Index (r=0.89). Strong intrarater (proSPI-s, saSPI-s, SPI-p, and SPI-i) and interrater (proSPI-s) reliability was demonstrated (all intraclass correlation coefficients >0.75). There were wide response distributions for all three components. We believe that both professional (proSPI) and self-assessed (saSPI) versions can readily be introduced into routine clinical practice.

Can stress reduction interventions improve psoriasis? A review.

Psoriasis remains incurable and many sufferers experience related psychological distress and a lower quality of life comparable with other chronic diseases. A subpopulation of people with psoriasis believes their condition is exacerbated by psychological stress. This review analyses whether stress-reduction interventions can reduce: the physical severity of psoriasis and related psychological distress. A systematic search across EMBASE, MEDLINE, The Cochrane Library SIGLE and PsychInfo, identified 730 trials and 10 were included. Three trials found a significant difference in psoriasis outcomes between groups post-intervention, (p < 0.05). Seven studies included a psychological outcome and three found a significant difference (p < 0.05). Three trials included a quality of life measurement and one of these reported a significant improvement (p < 0.001). Due to low quality evidence it is currently insufficient to judge stress reduction interventions as either effective or ineffective. We make nine recommendations for future research in this multidisciplinary field.

Topical treatments for scalp psoriasis.

Psoriasis is a common, chronic inflammatory skin disease that affects the scalp more commonly than any other site. Scalp psoriasis causes significant psychosocial disability as it is highly visible and can, on occasion, extend onto the face. Furthermore, current treatment regimens are messy, time consuming and, in some instances, ineffective, leading to a high level of non-compliance. The majority of current evidence for topical treatments for this condition comes from open-label, uncontrolled studies. From such studies, there are data to support the use of topical corticosteroids in a number of different formulations and topical vitamin D analogues. However, these studies have not addressed issues such as the need for keratolytics, which may be required to remove adherent scale before a topical corticosteroid or vitamin D analogue may prove efficacious. There is an urgent need for well designed, controlled trials to assess the efficacy of existing and new treatment regimens for scalp psoriasis. The aim of this review is to critically assess the relative effectiveness and tolerability of available topical therapies for this problematic condition and provide recommendations for selection of treatment.

Comparative effects of biological therapies on the severity of skin symptoms and health-related quality of life in patients with plaque-type psoriasis: a meta-analysis.

BACKGROUND: The comparative effects of biological response modifiers (BRMs) on the severity of psoriasis and its effects on health-related quality of life (HRQoL) have not been evaluated. OBJECTIVE: To conduct a meta-analysis to assess the effects of available biological agents on the severity of psoriasis, as well as to provide data on the effects of these agents on HRQoL. METHODS: Medline and other databases were searched for randomized controlled trials (>or= 10 weeks' duration in adults) comparing biological therapies for moderate-to-severe psoriasis with placebo. A Mantel-Haenszel fixed-effects model was employed to estimate the pooled relative risks (RR) of patients achieving >or= 75% reduction of baseline Psoriasis Area and Severity Index (PASI 75) after >or= 10 weeks of treatment. Similar analyses were also conducted on PASI 50 and PASI 90. Using a random-effects model, we estimated the likelihood of achieving PASI 50, PASI 75, and PASI 90 at 10-12 weeks and 24 weeks. Data on the effects of different BRMs (vs. placebo) on HRQoL were also presented. Numbers (%) of patients discontinuing treatment were presented as a general index of drug tolerability. RESULTS: Patients receiving infliximab 5 mg/kg intravenously at weeks 0, 2, and 6, then every 8 weeks, had the highest RR of achieving PASI 75, with a pooled RR value of 25.48 (95% confidence interval [CI], 14.04-46.23); followed by etanercept 50 mg administered subcutaneously (SC) twice weekly with RR = 11.92 (95% CI, 8.17-17.39); etanercept 25 mg SC twice weekly with RR = 10.68 (95% CI, 6.15-18.57); efalizumab 1-2 mg/kg SC per week with RR = 7.47 (95% CI, 5.20-10.73); and alefacept administered weekly (various doses) with RR = 3.37 (95% CI, 2.18-5.23). (All RR values were estimated vs. placebo.) Similar findings were observed with regard to proportions of patients achieving PASI 50 and PASI 90. The random-effects analysis suggested that infliximab significantly increased the likelihood of achieving PASI 50, PASI 75, and PASI 90 compared with placebo at 10-12 weeks; however, there were no significant differences between biological treatments at 24 weeks. Each BRM improved HRQoL compared with placebo according to findings from the Dermatology Life Quality Index. Proportions of patients discontinuing treatment were similar in active-treatment and placebo groups. CONCLUSIONS: Infliximab significantly reduced disease severity by both fixed- and random-effects models. All biological therapies improved HRQoL compared with placebo, and proportions of patients discontinuing treatment were similar in active-treatment and placebo groups. The analysis is potentially limited by statistical factors and did not systematically account for different toxicity profiles, but the findings establish a foundation for head-to-head comparative trials.