Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling.

Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 × 10-8, OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency < 0.01) via gene-wide aggregation testing (IFIH1: pburden = 2.53 × 10-7, OR = 0.707; TYK2: pburden = 6.17 × 10-4, OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.

Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture.

Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with PsA and 11 with PsC at genome-wide (GW) significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA; TNFRSF9, LCE3C/B, TRAF3IP2, IL23A, NFKBIA for PsC) have not previously achieved GW significance. After replication, we also identified a PsV-associated SNP near CDKAL1 (rs4712528, odds ratio [OR] = 1.16, p = 8.4 × 10(-11)). Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 × 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022). The PsA-specific variants were independent of previously identified psoriasis variants near IL23R and TNFAIP3. We also found multiple independent susceptibility variants in the IL12B, NOS2, and IFIH1 regions. These results provide insights into the pathogenetic similarities and differences between PsC and PsA.

Fine mapping major histocompatibility complex associations in psoriasis and its clinical subtypes.

Psoriasis vulgaris (PsV) risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but its genetic architecture has yet to be fully elucidated. Here, we conducted a large-scale fine-mapping study of PsV risk in the MHC region in 9,247 PsV-affected individuals and 13,589 controls of European descent by imputing class I and II human leukocyte antigen (HLA) genes from SNP genotype data. In addition, we imputed sequence variants for MICA, an MHC HLA-like gene that has been associated with PsV, to evaluate association at that locus as well. We observed that HLA-C(∗)06:02 demonstrated the lowest p value for overall PsV risk (p = 1.7 × 10(-364)). Stepwise analysis revealed multiple HLA-C(∗)06:02-independent risk variants in both class I and class II HLA genes for PsV susceptibility (HLA-C(∗)12:03, HLA-B amino acid positions 67 and 9, HLA-A amino acid position 95, and HLA-DQα1 amino acid position 53; p < 5.0 × 10(-8)), but no apparent risk conferred by MICA. We further evaluated risk of two major clinical subtypes of PsV, psoriatic arthritis (PsA; n = 3,038) and cutaneous psoriasis (PsC; n = 3,098). We found that risk heterogeneity between PsA and PsC might be driven by HLA-B amino acid position 45 (Pomnibus = 2.2 × 10(-11)), indicating that different genetic factors underlie the overall risk of PsV and the risk of specific PsV subphenotypes. Our study illustrates the value of high-resolution HLA and MICA imputation for fine mapping causal variants in the MHC.

From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis.

BACKGROUND: An urgent need exists in the United States to establish treatment goals in psoriasis. OBJECTIVE: We aim to establish defined treatment targets toward which clinicians and patients with psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice. METHODS: The National Psoriasis Foundation conducted a consensus-building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre-Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds. RESULTS: A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less. LIMITATIONS: Although BSA is feasible in practice, it does not encompass health-related quality of life, costs, and risks of side effects. CONCLUSION: With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit-risk assessments of therapeutic options individualized to the patient.

Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis.

Psoriasis is a common inflammatory disorder of the skin and other organs. We have determined that mutations in CARD14, encoding a nuclear factor of kappa light chain enhancer in B cells (NF-kB) activator within skin epidermis, account for PSORS2. Here, we describe fifteen additional rare missense variants in CARD14, their distribution in seven psoriasis cohorts (>6,000 cases and >4,000 controls), and their effects on NF-kB activation and the transcriptome of keratinocytes. There were more CARD14 rare variants in cases than in controls (burden test p value = 0.0015). Some variants were only seen in a single case, and these included putative pathogenic mutations (c.424G>A [p.Glu142Lys] and c.425A>G [p.Glu142Gly]) and the generalized-pustular-psoriasis mutation, c.413A>C (p.Glu138Ala); these three mutations lie within the coiled-coil domain of CARD14. The c.349G>A (p.Gly117Ser) familial-psoriasis mutation was present at a frequency of 0.0005 in cases of European ancestry. CARD14 variants led to a range of NF-kB activities; in particular, putative pathogenic variants led to levels >2.5× higher than did wild-type CARD14. Two variants (c.511C>A [p.His171Asn] and c.536G>A [p.Arg179His]) required stimulation with tumor necrosis factor alpha (TNF-α) to achieve significant increases in NF-kB levels. Transcriptome profiling of wild-type and variant CARD14 transfectants in keratinocytes differentiated probably pathogenic mutations from neutral variants such as polymorphisms. Over 20 CARD14 polymorphisms were also genotyped, and meta-analysis revealed an association between psoriasis and rs11652075 (c.2458C>T [p.Arg820Trp]; p value = 2.1 × 10(-6)). In the two largest psoriasis cohorts, evidence for association increased when rs11652075 was conditioned on HLA-Cw*0602 (PSORS1). These studies contribute to our understanding of the genetic basis of psoriasis and illustrate the challenges faced in identifying pathogenic variants in common disease.

Essential Truths for the Care and Management of Moderate-to-Severe Psoriasis.

Psoriasis is a systemic inflammatory disease. Effective management requires treatment with agents targeting inflammation in skin, joints, and other tissues. Biologics for psoriasis are directed at more specific targets, have a better safety profile, are better tolerated, and are more effective than conventional systemic agents. Despite these advances, many patients with psoriasis remain undertreated, and overall patient satisfaction remains low. The dichotomy between ideal therapeutic outcomes and suboptimal outcomes (which are currently commonplace) is likely largely due to misperceptions about psoriasis and biologic treatments. This article discusses these misperceptions, including the notions that psoriasis is a benign disorder, and that conventional systemic therapies are safer than biologics and adequate for most patients with moderate-to-severe disease. We present practical and evidence-based discussions to refute these misconceptions and provide useful resources for providers and patients that support access to advanced therapies. We believe that biologics represent optimal treatment for most patients with moderate-to-severe psoriasis, and until more effective approaches are generated, these efficacious and target-specific approaches should become the standard of care.

Impact of pigmentary disorders on quality of life in Japan: Interest of the BeautyQoL instrument.

Skin pigmentary disorders and uneven skin tone represent common cosmetic concerns in Japan where fairer skin is culturally desirable. As the demographics of Asian countries continue to evolve, there is a need to understand the impact of cosmetic skin concerns on quality of life (QoL). 199 Japanese women self-claiming facial skin pigmentation disorders were asked to complete the BeautyQoL questionnaire, and the results were compared with those of a control group of 200 women. Of the five dimensions of the BeautyQoL questionnaire, the dimension "mood" appeared to be significantly lower in the group presenting facial dark spots, as compared with the control group (p < 0.05). In the group presenting facial dark spots, the five dimensions and the global score showed that subjects concerned had lower scores than subjects less concerned, even if statistical significance was not reached. This study confirms that common pigmentary disorders such as facial black spots may negatively impact QoL. Further comparative studies with a controlled randomized design would be necessary to confirm these findings.

Clinical efficacy, radiographic and safety findings through 5†years of subcutaneous golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of a randomised, placebo-controlled trial (the GO-REVEAL study).

OBJECTIVES: Assess golimumab's long-term efficacy/safety in psoriatic arthritis (PsA). METHODS: Adults with active PsA (≥3 swollen and tender joints, active psoriasis) were randomly assigned to subcutaneous placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks (q4wks) through wk20. All patients received golimumab 50 mg or 100 mg q4wks from wk24 forward. Methotrexate was allowed and taken by approximately half the patients. Findings through 5 years are reported herein. Efficacy assessments included ≥20% improvement in American College of Rheumatology (ACR20) response, C-reactive-protein-based, 28-joint-count Disease Activity Score (DAS28-CRP) response, ≥75% improvement in Psoriasis Area and Severity Index (PASI75) scores, and PsA-modified Sharp/van der Heijde scores (SHSs). RESULTS: 126/405 (31%) randomised patients discontinued treatment through wk252. Golimumab was effective in maintaining clinical improvement through year-5 (ACR20: 62.8-69.9%, DAS28-CRP: 75.2-84.9% for randomised patients; PASI75: 60.8-72.2% among randomised patients with ≥3% body surface area involvement) and inhibiting radiographic progression (mean changes in PsA-modified SHS: 0.1-0.3) among patients with radiographic data. While concomitant methotrexate did not affect ACR20/PASI75, it appeared to reduce radiographic progression. No new safety signals were identified. Antibodies-to-golimumab occurred in 1.8%/10.0% of patients with/without methotrexate). CONCLUSIONS: Long-term golimumab safety/efficacy in PsA was demonstrated through 5 years. TRIAL REGISTRATION NUMBER: NCT00265096.

Patient-reported outcomes for psoriasis patients with clear versus almost clear skin in the clinical setting.

BACKGROUND: There is little evidence to guide the establishment of treatment goals for moderate to severe psoriasis in the clinical setting. OBJECTIVE: We sought to compare Dermatology Life Quality Index scores and prescription topical medication use between patients with clear versus almost clear skin. METHODS: This was a multicenter cross-sectional study of 97 patients with clear skin and 441 patients with almost clear skin receiving current systemic therapy or phototherapy for a primary indication of plaque psoriasis evaluated at 1 of 10 US outpatient dermatology sites participating in the Dermatology Clinical Effectiveness Research Network. RESULTS: In adjusted analyses, patients with clear versus almost clear skin were more likely to report no impact of psoriasis on quality of life (relative risk 1.60; 95% confidence interval 1.37-1.86). Patients with clear versus almost clear skin were also more likely to report no prescription topical medication use in the preceding week (relative risk 2.08; 95% confidence interval 1.73-2.49). LIMITATIONS: Cross-sectional design prohibits longitudinal assessment of outcomes. CONCLUSIONS: Clinically important differences in quality of life and prescription topical medication use exist between patients with clear versus almost clear skin. Collectively, our results indicate that achievement of clear skin may be an important clinical distinction among patients with moderate to severe psoriasis.

Palmoplantar psoriasis is associated with greater impairment of health-related quality of life compared with moderate to severe plaque psoriasis.

BACKGROUND: The impact of palmoplantar psoriasis on health-related quality of life (QoL) is largely unknown. OBJECTIVE: We sought to compare clinical characteristics and patient-reported outcomes between patients with palmoplantar psoriasis and moderate to severe plaque psoriasis. METHODS: We conducted a cross-sectional study of patients with plaque psoriasis (N=1153) and palmoplantar psoriasis (N=66) currently receiving systemic or light treatment for psoriasis. RESULTS: Patients with palmoplantar psoriasis were more likely to report Dermatology Life Quality Index scores that correspond to at least a moderate impact on QoL (odds ratio [OR] 2.08; 95% confidence interval [CI] 1.20-3.61); problems with mobility (OR 1.98; 95% CI 1.10-3.58), self-care (OR 3.12; 95% CI 1.24-7.86), and usual activities (OR 2.47; 95% CI 1.44-4.22) on the European Quality of Life-5 Dimensions questionnaire; and heavy topical prescription use of at least twice daily in the preceding week (OR 2.81; 95% CI 1.63-4.85) than those with plaque psoriasis. LIMITATIONS: Our assessment tools may not account for all dimensions of health-related QoL affected by palmoplantar disease, and these results may not be generalizable to patients with milder forms of psoriasis. CONCLUSION: Patients with palmoplantar psoriasis experience greater health-related QoL impairment and are more likely to report heavy use of topical prescriptions than those with moderate to severe plaque psoriasis.

Comparative effectiveness of less commonly used systemic monotherapies and common combination therapies for moderate to severe psoriasis in the clinical setting.

BACKGROUND: The effectiveness of psoriasis therapies in real-world settings remains relatively unknown. OBJECTIVE: We sought to compare the effectiveness of less commonly used systemic therapies and commonly used combination therapies for psoriasis. METHODS: This was a multicenter cross-sectional study of 203 patients with plaque psoriasis receiving less common systemic monotherapy (acitretin, cyclosporine, or infliximab) or common combination therapies (adalimumab, etanercept, or infliximab and methotrexate) compared with 168 patients receiving methotrexate evaluated at 1 of 10 US outpatient dermatology sites participating in the Dermatology Clinical Effectiveness Research Network. RESULTS: In adjusted analyses, patients on acitretin (relative response rate 2.01; 95% confidence interval [CI] 1.18-3.41), infliximab (relative response rate 1.93; 95% CI 1.26-2.98), adalimumab and methotrexate (relative response rate 3.04; 95% CI 2.12-4.36), etanercept and methotrexate (relative response rate 2.22; 95% CI 1.25-3.94), and infliximab and methotrexate (relative response rate 1.72; 95% CI 1.10-2.70) were more likely to have clear or almost clear skin compared with patients on methotrexate. There were no differences among treatments when response rate was defined by health-related quality of life. LIMITATIONS: Single time point assessment may result in overestimation of effectiveness. CONCLUSIONS: The efficacy of therapies in clinical trials may overestimate their effectiveness as used in clinical practice. Although physician-reported relative response rates were different among therapies, absolute differences were small and did not correspond to differences in patient-reported outcomes.

Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): experience with infliximab and other systemic and biologic therapies.

BACKGROUND: Long-term data are essential to assess the safety of biologic agents for the treatment of psoriasis. OBJECTIVE: To evaluate the incidence of adverse events of interest (AEIs), including all-cause mortality, major adverse cardiovascular events (MACE), malignancy (excluding nonmelanoma skin cancer), and serious infections (SI), in patients treated for psoriasis in clinical practice settings. METHODS: PSOLAR is a large, ongoing, observational study of patients receiving, or eligible to receive, biologic or systemic therapy for psoriasis. Cumulative incidence rates of AEIs per 100 patient-years (PY) are reported across treatment cohorts: (1) infliximab, (2) ustekinumab, (3) other biologics (eg, adalimumab and etanercept), and (4) non-biologic agents. Significant predictors of each AEI were identified using Cox proportional hazards regression methodology. RESULTS: PSOLAR is now fully enrolled at 12095 patients followed for 31818PY. The cumulative rate was 0.46/100PY for death, 0.36/100PY for MACE, 0.68/100PY for malignancy, and 1.50/100PY for SI. Increasing age was a significant predictor of all AEIs. A history of cardiovascular disease, malignancy, and significant infection was associated with a higher risk of developing MACE, malignancy, and SI, respectively. Exposure to infliximab (Hazard Ratio [HR]=3.101, P<0.001) and exposure to other biologics (HR=1.736, P<0.001) were significant predictors of SI. Use of immunomodulators (HR=1.954, P=0.005) was a significant predictor of MACE. Compared with non-biologic therapy, the use of biologic agents was not a significant predictor of death, MACE, or malignancy. CONCLUSIONS: Based on PSOLAR data through 2013, no new safety concerns were observed with infliximab for all-cause mortality, MACE, or malignancy; the data suggest that infliximab was associated with serious infections.

PAPRIKA: A Question Bank for Assessing Psoriatic Arthritis Risk in Individuals of Diverse Ancestries.

OBJECTIVE: We aimed to create a question bank about clinical factors for predicting the diagnoses of psoriatic arthritis in patients with psoriasis of various ancestries and skin tones, which can be completed entirely by patients. METHODS: Utah Psoriasis Initiative participants without a psoriatic arthritis diagnosis at enrollment were observed for diagnosis during the study period. We inferred ancestry from exome sequencing data and performed Cox proportional hazards regression to identify clinical predictors of psoriatic arthritis in different ancestry groups. Based on results and literature review, we developed a question bank for assessing psoriatic arthritis risk among patients with psoriasis in various ancestries. RESULTS: Patient-reported untreated psoriasis induration and history of fingernail psoriasis were associated with psoriatic arthritis in participants of European and non-European ancestry. We developed the Psoriatic Arthritis Prediction and Identification Question Bank for Diverse Ancestries (PAPRIKA) version 1.0, which included questions regarding psoriasis characteristics, arthritis symptoms, comorbidities, family history, and demographics. PAPRIKA is accessible at http://bjfenglab.org/. CONCLUSION: The clinical features (untreated psoriasis induration and history of fingernail psoriasis) that can predict psoriatic arthritis in European individuals also work for non-European individuals. PAPRIKA can be used to gather psoriatic arthritis predictive data from patients with psoriasis without provider assistance and is relevant for patients across ancestries.

Measuring Psoriasis Severity at Home.

Psoriasis plaque severity metrics, such as induration (thickness), erythema (redness), and desquamation (scaliness), are associated with the subsequent development of psoriatic arthritis (PsA) among cutaneous-only psoriasis patients (patients with skin or nail psoriasis but no psoriatic arthritis). These metrics can be used for PsA screening. However, a key challenge in PsA screening is to optimize accessibility and minimize costs for patients, while also reducing the burden on healthcare systems. Therefore, an ideal screening tool consists of questions that patients can answer without a physician's assistance. Although reference images can be used to help a patient self-assess erythema and desquamation severity, a patient would need a tactile induration reference card to self-assess induration severity. This protocol describes how to create an induration reference card, the Psoriasis Thickness Reference Card, as well as how to use it to assess lesion induration severity. Administration of reference images for erythema and desquamation and a Psoriasis Thickness Reference Card for induration to 27 psoriasis patients showed that patients were moderately successful at self-assessing the severity of these three metrics. These findings support the feasibility of a future PsA screening test that patients can complete without the need for physician assistance.

Markers of inflammation and bone remodelling associated with improvement in clinical response measures in psoriatic arthritis patients treated with golimumab.

OBJECTIVE: To determine serum biomarker associations with clinical response to golimumab treatment in patients with psoriatic arthritis (PsA). METHODS: GO-REVEAL was a randomised, placebo-controlled study of golimumab in patients with active PsA. Samples were collected from 100 patients at baseline, week 4 and week 14, and analysed for serum-based biomarkers and protein profiling (total 92 markers); data were correlated with clinical measures at week 14. RESULTS: Serum levels of a subset of proteins (apolipoprotein C III, ENRAGE, IL-16, myeloperoxidase, vascular endothelial growth factor, pyridinoline, matrix metalloproteinase 3, C-reactive protein (CRP), carcinoembryonic antigen, intercellular adhesion molecule 1 and macrophage inflammatory protein 1α) at baseline or week 4 were strongly associated with American College of Rheumatology 20% improvement (ACR20) response and/or disease activity score in 28 joints (DAS28) at week 14. A smaller subset of proteins was significantly associated with a 75% improvement in the psoriasis area and severity index score (PASI75) at week 14, (adiponectin, apolipoprotein CIII, serum glutamic oxaloacetic transaminase, and tumour necrosis factor α). Subsets of proteins were identified as potentially predictive of clinical response for each of the clinical measures, and the power of these biomarker panels to predict clinical response to golimumab treatment was stronger than for CRP alone. CONCLUSIONS: This analysis provides insight into several panels of markers that may have utility in identifying PsA patients likely to have ACR20, DAS28, or PASI75 responses following golimumab treatment.

Clinical efficacy, radiographic and safety findings through 2 years of golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of the randomised, placebo-controlled GO-REVEAL study.

OBJECTIVES: To assess long-term golimumab efficacy/safety in patients with active psoriatic arthritis (PsA). METHODS: Adult PsA patients (≥3 swollen, ≥3 tender joints, active psoriasis) were randomly assigned to subcutaneous injections of placebo, golimumab 50 mg or 100 mg every 4 weeks (q4wks) through week 20. All patients received golimumab 50 or 100 mg beginning week 24. Findings through 2 years are reported. Efficacy evaluations included ≥20% improvement in American College of Rheumatology (ACR20) response, good/moderate response in Disease Activity Scores incorporating 28 joints and C-reactive protein (DAS28-CRP), ≥75% improvement in Psoriasis Area and Severity Index (PASI75) and changes in PsA-modified Sharp/van der Heijde scores (SHS). RESULTS: Golimumab treatment through 2 years was effective in maintaining clinical response (response rates: ACR20 63%-70%, DAS28-CRP 77%-86%, PASI75 56%-72%) and inhibiting radiographic progression (mean change in PsA-modified SHS in golimumab-treated patients: -0.36), with no clear difference between doses. No new safety signals were identified through 2 years. With the study's tuberculosis screening and prophylactic measures, no patient developed active tuberculosis through 2 years. CONCLUSIONS: Golimumab 50 and 100 mg for up to 2 years yielded sustained clinical and radiographic efficacy when administered to patients with active PsA. Increasing the golimumab dose from 50 to 100 mg q4wks added limited benefit. Golimumab safety through up to 2 years was consistent with other antitumour necrosis factor α agents used to treat PsA. Treatment of patients with latent tuberculosis identified at baseline appeared to be effective in inhibiting the development of active tuberculosis.

Product of the Physician Global Assessment and body surface area: a simple static measure of psoriasis severity in a longitudinal cohort.

BACKGROUND: The Psoriasis Area and Severity Index (PASI) is considered the gold standard assessment tool for psoriasis severity, but PASI is limited by its complexity and insensitivity in people with mild psoriasis. OBJECTIVE: We sought to evaluate the product of a Physician Global Assessment (PGA) and Body Surface Area (BSA) (PGAxBSA) as an alternative to PASI. METHODS: Psoriasis severity was evaluated at 6-month intervals in participants of the Utah Psoriasis Initiative registry. Correlation coefficients were used to compare PGAxBSA with PASI and the Simplified PASI (SPASI). RESULTS: Between August 2008 and November 2010, 435 assessments were completed in 226 participants. The median PASI score was 3.2 (interquartile range 1.8-5.4) and the median BSA was 3.0% (interquartile range 1.0%-5.0%). PGAxBSA had higher correlations with PASI than SPASI (0.87 vs 0.76, P < .001). PGAxBSA also had higher correlations with a Global Patient Assessment of psoriasis severity (0.65) than both PASI (0.59, P < .001) and SPASI (0.51, P < .001). LIMITATIONS: The use of PGAxBSA for measuring severe psoriasis and response to therapy is unclear, because most participants had mild to moderate psoriasis and data were not collected at predefined intervals in relation to therapy initiation. Interrater reliability was not assessed. CONCLUSIONS: PGAxBSA is a simple and sensitive instrument for measuring psoriasis severity.

Variation in dermatologist beliefs about the safety and effectiveness of treatments for moderate to severe psoriasis.

BACKGROUND: Multiple systemic treatments are available for moderate to severe psoriasis, but dermatologists' perceptions of these treatments are unknown. Physician perceptions can influence prescribing patterns and patient outcomes, and may help to explain variations in clinical practice. OBJECTIVE: We sought to describe the variation in dermatologist's beliefs about the safety and effectiveness of psoriasis treatments and evaluate how these relate to dermatologist characteristics and treatment preferences. METHODS: We conducted a cross-sectional mail survey of a random sample of 500 National Psoriasis Foundation (NPF) members and 500 American Academy of Dermatology (AAD) members who treat psoriasis. RESULTS: Of 989 clinicians who could be contacted, 246 NPF members and 141 AAD members returned the survey (39% response rate). Respondents perceived infliximab, ustekinumab, cyclosporine, and adalimumab to have the highest likelihood of skin clearance in 3 months (67%-75%). Etanercept, adalimumab, ultraviolet B, and ustekinumab had the lowest perceived likelihood of side effects requiring treatment discontinuation (9%-11%). Up to 49% of respondents "didn't know" the effectiveness or likelihood of side effects; calculated coefficients of variation were higher for perceived likelihood of side effects than perceived effectiveness. There were few significant associations between safety and effectiveness perceptions and respondent characteristics, and treatment preferences were not consistently predictive of perceptions. LIMITATIONS: Only dermatologists with interest in treating psoriasis were surveyed and general perceptions were elicited via survey format. Perceptions may differ between survey respondents and nonrespondents. CONCLUSIONS: Psoriasis providers demonstrate wide variation in their perception of the effectiveness and especially safety of systemic treatments.

Patient-reported reasons for the discontinuation of commonly used treatments for moderate to severe psoriasis.

BACKGROUND: Despite widespread dissatisfaction and low treatment persistence in moderate to severe psoriasis, patients' reasons behind treatment discontinuation remain poorly understood. OBJECTIVES: We sought to characterize patient-reported reasons for discontinuing commonly used treatments for moderate to severe psoriasis in real-world clinical practice. METHODS: A total of 1095 patients with moderate to severe plaque psoriasis from 10 dermatology practices who received systemic treatments completed a structured interview. Eleven reasons for treatment discontinuation were assessed for all past treatments. RESULTS: A total of 2231 past treatments were reported. Median treatment duration varied by treatment, ranging from 6.0 to 20.5 months (P < .001). The frequency of each cited discontinuation reasons differed by treatment (all P < .01). Patients who received etanercept (odds ratio [OR] 5.19; 95% confidence interval [CI] 3.23-8.33) and adalimumab (OR 2.10; 95% CI 1.20-3.67) were more likely to cite a loss of efficacy than those who received methotrexate. Patients who received etanercept (OR 0.34; 95% CI 0.23-0.49), adalimumab (OR 0.48; 95% CI 0.30-0.75), and ultraviolet B phototherapy (OR 0.21; 95% CI 0.14-0.31) were less likely to cite side effects than those who received methotrexate, whereas those who received acitretin (OR 1.56; 95% CI 1.08-2.25) were more likely to do so. Patients who underwent ultraviolet B phototherapy were more likely to cite an inability to afford treatment (OR 7.03; 95% CI 3.14-15.72). LIMITATIONS: The study is limited by its reliance on patient recall. CONCLUSIONS: Different patterns of treatment discontinuation reasons are important to consider when developing public policy and evidence-based treatment approaches to improve successful long-term psoriasis control.

Golimumab in psoriatic arthritis: one-year clinical efficacy, radiographic, and safety results from a phase III, randomized, placebo-controlled trial.

OBJECTIVE: Golimumab, administered subcutaneously every 4 weeks, has been shown to be effective in reducing the signs and symptoms of active psoriatic arthritis (PsA) through week 24 of the GO-REVEAL study. Herein we report 1-year clinical, radiographic, and safety findings. METHODS: Adult patients with active PsA (≥3 swollen and ≥3 tender joints) were randomly assigned to receive subcutaneous placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks through week 20. At week 16, patients with <10% improvement from baseline in swollen and tender joint counts entered a blinded early escape phase, with placebo crossover to golimumab 50 mg, golimumab 50 mg increased to 100 mg, and golimumab 100 mg continued at 100 mg. Patients receiving placebo who did not enter the early escape phase crossed over to golimumab 50 mg at week 24. Findings through 1 year are reported, including the second of 2 coprimary end points (i.e., change from baseline to week 24 in PsA-modified Sharp/van der Heijde score [SHS]). RESULTS: A total of 405 patients were randomized: 113 to placebo and 146 each to the golimumab 50 mg and 100 mg groups. Mean changes in PsA-modified SHS from baseline to week 24 for the combined golimumab 50 mg and 100 mg group (-0.09) and the golimumab 50 mg group (-0.16) were significantly different versus placebo (0.27) (P = 0.015 and P = 0.011, respectively). Radiographic benefit was maintained through week 52 with golimumab. Clinical efficacy, including improvement in joint and skin responses and physical function, was maintained through 1 year. The frequency/types of adverse events were similar to those reported through week 24. CONCLUSION: Treatment of PsA with golimumab inhibited structural damage progression and demonstrated continued clinical efficacy and safety through 1 year.