Psoriasis Publications

BACKGROUND: An unmet need remains for safe and effective long-term treatments of psoriasis.

OBJECTIVES: To evaluate ustekinumab efficacy and safety for up to 3 years in the PHOENIX 1 trial.

METHODS: Patients (n = 766) with moderate-to-severe psoriasis were randomized to ustekinumab 45 mg or 90 mg at weeks 0 and 4, and then every 12 weeks, or placebo at weeks 0 and 4, with crossover to ustekinumab at week 12. Ustekinumab responders [≥ 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at weeks 28 and 40] were re-randomized at week 40 to continue or withdraw from treatment until psoriasis recurrence. Partial responders (week 28: PASI 50-74; week 40: < PASI 75) switched to dosing every 8 weeks. Clinical efficacy was assessed by PASI, the Physician's Global Assessment (PGA), and the Dermatology Life Quality Index (DLQI) measures.

RESULTS: Overall, 79·8% of the ustekinumab-treated patients remained in the study for 3 years. PASI 75 response rates (45 mg: 61·2%; 90 mg: 72·4%) at week 76 were maintained through year 3 (45 mg: 62·7%; 90 mg: 72·2%); PGA response was similarly durable. At year 3, 80·9% (45 mg) and 82·7% (90 mg) of week 40 responders continuing treatment every 12 weeks achieved a PASI 75 response, while 42·6% (45 mg) and 58·0% (90 mg) achieved a PASI 90 response. Among partial responders adjusted to dosing every 8 weeks, 50·9% (45 mg) and 52·0% (90 mg) had a PASI 75 response at year 3. DLQI responses paralleled the PASI responses. Through year 3, no dose response was observed in rates of adverse events (AEs), overall infections, serious AEs, or AEs leading to discontinuation; nor was there evidence of cumulative organ toxicity. CONCLUSIONS; Continuous, stable, maintenance dosing with ustekinumab was generally well tolerated and sustained durable efficacy for up to 3 years of treatment.

BACKGROUND: Ustekinumab targets interleukin (IL)-12 and IL-23 in the treatment of moderate to severe psoriasis.

OBJECTIVE: We sought to evaluate the impact of ustekinumab on infections and malignancies, both theoretical risks of blocking IL-12 and IL-23, in patients exposed up to 3 years.

METHODS: Rates of infections and malignancies were evaluated in cumulative safety data from 3117 ustekinumab-treated patients across 4 studies.

RESULTS: During the placebo-controlled periods, rates of overall infections per 100 patient-years were similar among placebo (121.0), ustekinumab 45-mg (145.7), and ustekinumab 90-mg (132.2) groups, with overlapping confidence intervals, and remained stable through 3 years in ustekinumab groups. Rates of serious infections during the placebo-controlled periods were similar between placebo (1.70) and 90-mg (1.97) groups, yet lower in the 45-mg group (0.49). Rates remained stable (90 mg) or decreased (45 mg) over time, and were comparable with those for the US psoriasis population based on a managed care database. Rates of malignancies during the placebo-controlled periods were comparable among groups (placebo: 1.70; 45 mg: 0.99; 90 mg: 0.98) and remained stable over time in ustekinumab groups. Rates of malignancies, excluding nonmelanoma skin cancer, were comparable with rates expected in the general US population based on the Surveillance, Epidemiology, and End Results database.

LIMITATIONS: Controlled periods do not extend beyond 12 to 20 weeks. Only 1247 patients were treated for at least 2 years, to date. Comparator database populations may not fully represent the clinical trial population.

CONCLUSIONS: The emerging safety profile of ustekinumab remains favorable and does not suggest increased rates of infection or malignancy through 3 years.

BACKGROUND: Psoriasis has a profound negative effect on quality of life that is often underappreciated by health care professionals and the public.

OBJECTIVE: We sought to assess the perception of the burden of psoriasis relative to other medical conditions in first-year medical students, and to determine if wearing a temporary tattoo simulating psoriasis during a teaching exercise would change their perceptions.

METHODS: Participants completed a questionnaire assessing their perception of the impact of psoriasis and other common medical conditions (visual analog scale). Participants then wore a temporary tattoo of a psoriatic lesion for 24 hours and completed the same questionnaire after this exercise.

RESULTS: Of 91 students approached, 61 completed the study. At baseline, psoriasis (mean = 23.6) and eczema (mean = 23.3) were perceived as having the lowest physical burden of diseases queried (P < .0001), whereas the mental impact of psoriasis was scored comparably with arthritis, heart disease, and diabetes (mean = 45.1-56.7), but lower than cancer (mean = 82.2) and depression (mean = 93.8). After the exercise, the perception of the impact of eczema (physical: mean = 37.3, P < .0001; mental: mean = 66.6, P = .0005) and psoriasis (physical: mean = 37.8, P = .0014; mental: mean = 68.6, P = .0293) was significantly increased.

LIMITATIONS: The exercise did not simulate the chronic nature of psoriasis or the scaling and pruritic characteristics of psoriatic lesions. The survey instrument used to assess empathy has not been previously validated and statistical analysis was limited by small sample size and the absence of a control group.

CONCLUSIONS: Temporary tattoos are a novel and effective method of teaching medical students about the psychological burden of psoriasis.

BACKGROUND: Patients with psoriasis are known to have an increased number of cardiovascular (CV) risk factors and be at increased risk for CV events.

OBJECTIVES: We sought to describe and characterize the underdiagnosis and undertreatment of CV risk factors in patients with moderate to severe psoriasis.

METHODS: Medical histories including diabetes, hypertension, and hyperlipidemia were obtained from 2899 patients in 3 phase III ustekinumab trials, a therapeutic anti-interleukin (IL)-12/IL-23p40 monoclonal antibody. Reported history was compared with measured fasting glucose, fasting lipids, and blood pressure. Ten-year Framingham risk scores and the proportion of patients achieving glycemic, lipid, and blood pressure targets were evaluated.

RESULTS: Significant risk factors existed in patients with moderate to severe psoriasis (58.6% and 28.8% of patients had ≥ 2 and ≥ 3 established CV risk factors, respectively). Based on Framingham risk score, 18.6% of patients were at high risk and 12.3% were at intermediate risk for CV events. At baseline, a small proportion of patients with diabetes (2.3%), hypertension (9.1%), or hyperlipidemia (4.9%) were previously without a diagnosis. However, 19.1%, 21.8%, and 38.6% of patients with diabetes, hypertension, or hyperlipidemia, respectively, were untreated at baseline, and the proportion at treatment goal was not ideal (hypertension 59.6% and hyperlipidemia 69.7%), especially for diabetes (36.7%).

LIMITATIONS: Results are based on a clinical trial population and findings may not be generalizable to the general psoriasis population.

CONCLUSIONS: In this moderate to severe psoriasis population, a high prevalence of undiagnosed and undertreated CV risk factors existed, emphasizing the importance of screening patients with psoriasis for CV risk factors.

BACKGROUND: Treating psoriasis in pregnant and lactating women presents a special challenge. For ethical reasons, prospective randomized control trials have not been conducted in this patient population although these patients do encounter new-onset psoriasis in addition to flares and may require treatment throughout their pregnancies.

OBJECTIVE: Our aim was to arrive at consensus recommendations on treatment options for psoriasis in pregnant and lactating women.

METHODS: The literature was reviewed regarding all psoriasis therapies in pregnant and lactating women.

RESULTS: Topical therapies including emollients and low- to moderate-potency topical steroids are first-line therapy for patients with limited psoriasis who are pregnant or breast-feeding. The consensus was that second-line treatment for pregnant women is narrowband ultraviolet B phototherapy or broadband ultraviolet B, if narrowband ultraviolet B is not available. Lastly, tumor necrosis factor-α inhibitors including adalimumab, etanercept, and infliximab may be used with caution as may cyclosporine and systemic steroids (in second and third trimesters). Some specific strategies may be used to minimize risk and exposure.

LIMITATIONS: There are few evidence-based studies on treating psoriasis in pregnant and lactating women.

CONCLUSIONS: Because there will always be a question of ethical concerns placing pregnant and lactating women in prospective clinical trials, investigation of both conventional and biologic agents are unlikely to ever be performed. Some of these medications used to treat psoriasis are known abortifacients, mutagens, or teratogens and must be clearly avoided but others can be used with relative confidence in select patients with appropriate counseling of risks and benefits.

BACKGROUND: Symptoms of psoriasis can be embarrassing and distressing, and may increase risk of developing psychiatric disorders in young people.

OBJECTIVE: We sought to compare incidences of psychiatric disorders between pediatric patients with psoriasis and psoriasis-free control subjects.

METHODS: Patients (<18 years) with continuous health plan enrollment 6 months before and after first psoriasis diagnosis (index date) were selected (Thomson Reuters MarketScan database, 2000-2006 [Thomson Reuters, New York, NY]). Patients with psoriasis (N = 7404) were matched 1:5 on age and sex to psoriasis-free control subjects (N = 37,020). Patients were followed from index date to first diagnosis of a psychiatric disorder (ie, alcohol/drug abuse, depression, anxiety disorder, bipolar disorder, suicidal ideation, eating disorder), end of data availability, or disenrollment. Patients with psychiatric diagnoses or psychotropic medication use before the index date were excluded. Cox proportional hazard models controlling for age, sex, and comorbidities were used to estimate the effect of psoriasis on risks of developing psychiatric disorders.

RESULTS: Patients with psoriasis were significantly more at risk of developing psychiatric disorders versus control subjects (5.13% vs 4.07%; P = .0001; hazard ratio = 1.25; P = .0001), especially depression (3.01% vs 2.42%; P = .0036; hazard ratio = 1.25; P = .0053) and anxiety (1.81% vs 1.35%; P = .0048; hazard ratio = 1.32; P = .0045).

LIMITATIONS: Retrospective, observational studies of medical claims data are typically limited by overall quality and completeness of data and accuracy of coding for diagnoses and procedures.

CONCLUSIONS: Pediatric patients with psoriasis had an increased risk of developing psychiatric disorders, including depression and anxiety, compared with psoriasis-free control subjects.

BACKGROUND: Long-term observational studies can better characterize the impact of systemic agents on psoriasis.

OBJECTIVE: To describe the on-going Psoriasis Longitudinal Assessment and Registry (PSOLAR) study.

METHODS: PSOLAR is a large, international, long-term, prospective, disease-based registry enrolling patients with psoriasis who are receiving, or are candidates for, treatment with systemic therapies. The registry fulfills postmarketing regulatory commitments and charges a global Steering Committee to manage epidemiological research on psoriasis and its therapies. Key demographics, disease characteristics, and medication history are collected at enrollment. Adverse events and efficacy data are collected longitudinally.

RESULTS: The August 2011 annual database extract includes 9,495 patients enrolled at 266 global centers. At entry, mean percent of body surface area affected by psoriasis was 12.3% (peak, 29.5%). Approximately 80% of patients were overweight/obese, more than one-third had cardiovascular disease (38.8%) or psoriatic arthritis as captured by the treatment center (37.1%), and over half had received one or two biologic agents (58.8%) or phototherapy (54.8%). Mean duration of participation is 1.3 years, and annual withdrawal rates are less than 6.5%. Of 9,495 patients, 7,476 have been exposed to at least one biologic agent. Serious infections, malignancies, all-cause mortality, and major adverse cardiovascular events (ie, myocardial infarction, stroke, cardiovascular death) occurred at rates of 1.40, 0.61, 0.37, and 0.36 per 100 patient-years of follow-up, respectively.

LIMITATIONS: PSOLAR may be subject to limitations common to observational studies (eg, participation bias and potential confounders).

CONCLUSION: PSOLAR is a disease-based registry designed to assess therapeutic risk and benefit in the general psoriasis population.

Psoriasis is a common chronic dermatological disease whose prevalence varies among different populations worldwide. In epidemiological studies, the factors that potentially account for this variability include climate, genetic susceptibility, and environmental antigen exposure. In this issue, Parisi et al. performed a systematic review to explore the global prevalence and incidence of psoriasis.

BACKGROUND: Etanercept is approved for the treatment of chronic moderate to severe plaque psoriasis in adults.

OBJECTIVE: We sought to evaluate the long-term safety of etanercept in a real-world clinical setting. Assessment of etanercept efficacy was a secondary objective.

METHODS: OBSERVE-5 is a 5-year observational safety registry initiated in May 2006 at multiple sites in the United States and Canada. Data collection includes the number of serious adverse events, serious infectious events, and prespecified events of medical interest. Efficacy data include body surface area assessments, physician and patient global assessments of psoriasis, and the Dermatology Life Quality Index. This interim analysis presents data from the first 3 years of the follow-up period.

RESULTS: A total of 2511 patients were enrolled. Of 1890 patients continuing in the registry after 3 years, 113 were inactive for 1 to 2 years, and 115 were inactive for longer than 2 years. The 3-year incidence proportions of serious adverse events and serious infectious events based on Kaplan-Meier methodology were 0.14 and 0.04, respectively. The observed numbers of patients experiencing lymphoma, serious infectious events requiring hospitalization, nonmelanoma skin cancer, and malignancies excluding nonmelanoma skin cancer were not higher than the expected number of cases estimated from a large US administrative health claims database.

LIMITATIONS: The registry lacks a control group, and the study is too small to measure the frequency of rare events.

CONCLUSION: Etanercept demonstrated good tolerability in patients with plaque psoriasis in the clinical setting in this interim analysis. No new or unexpected safety concerns were observed.

BACKGROUND: Validated epidemiological estimates of the prevalence of skin diseases remain an unmet challenge. Most patients in many health care systems do not see dermatologists for skin problems. Assessments based on claims data or self-report are likely to contain substantial misclassification. Population-based in-person dermatological exams have proven impractical because of the number of patients required. However, in the US, there is a large skin cancer screening program where volunteer dermatologists assess almost 100,000 people annually.

OBJECTIVE: To evaluate the utility of this program for the assessment of other diseases.

METHODS: Information concerning prior diagnosis of psoriasis, type of insurance and physician's current assessment of psoriasis was captured as part of the American Academy of Dermatology National Melanoma/Skin Cancer Screening Program. A modified form was provided to a subset of participant sites. Overall and subgroup prevalence of psoriasis was analysed. Crude and adjusted results are presented for comparison to the US population.

RESULTS: Among the 2991 participants, 86% answered the self-report psoriasis question. A previous diagnosis of psoriasis was reported by 5.1% of them. This proportion was greater than the prevalence of physician documented diagnosis of psoriasis (2.8%). Analyses with different assumptions to account for missing values and weighting based on US population estimates yielded prevalence values ranging from 1.2% to 3.4%.

CONCLUSION: This project, although limited by missing data, is consistent with previous findings that psoriasis prevalence is between 2.2% and 4.6% in the US. It demonstrates the potential to evaluate prevalence of other skin conditions through existing national activities.

Psoriasis is a disease state that may present significant cumulative life course impairment (CLCI). The impact of psoriasis on CLCI can be divided into social factors such as stigmatization, psychological factors such as depression, and physical factors such as pruritis, pain and arthritis. With a bimodal age range at first presentation, psoriasis tends to affect those in the second and fifth decades of life. In accordance with the CLCI model, the age of first presentation may substantially affect an individuals' life course, with younger patients more susceptible to CLCI. Social, psychological, and physical factors also provide protection from CLCI: personality, coping mechanisms, social support, and treatment or therapy may act as positive factors and mitigate these damaging effects. As the time course of most clinical trials encompasses a fraction of a patients' life, the true nature of this impact has not been easily captured. Longitudinal CLCI data in psoriasis is limited and continued life course data is needed.

OBJECTIVE: To develop and assess content validity of the Psoriasis Symptom Inventory (PSI), a patient-reported outcome (PRO) measure of psoriasis symptoms.

METHODS: Following initial literature exploration and input from experts, concept elicitation was conducted in two rounds (focus groups and individual interviews) with 59 subjects with mild to severe psoriasis. Transcripts were coded to identify symptom concepts and develop a conceptual framework using ATLAS.ti software. Qualitative content analysis and clinical expert input supported item generation and development of a draft measure. Two rounds of face-to-face cognitive interviews with 40 subjects with moderate to severe psoriasis were conducted to test subject comprehension and content coverage.

RESULTS: Concepts of itching, scaling, flaking, tearing/cracking, burning, stinging, pain, bleeding and color of appearance were the most common symptom-related expressions. Saturation of concept was demonstrated. Severity was identified as the most meaningful attribute of psoriasis symptoms. A final 8-item measure was developed to assess patient-perceived symptom severity for itch, pain, burning, stinging, cracking, scaling, flaking and redness. Twenty-four-hour recall and 7-day recall versions were prepared for future quantitative assessment of measurement properties.

CONCLUSIONS: The PSI is a short, low burden, patient-reported measure of psoriasis symptom severity with documented evidence of content validity.

BACKGROUND: Ongoing evaluation of biological agents in patients with moderate-to-severe psoriasis is needed to support their long-term use.

OBJECTIVE: To evaluate long-term efficacy and safety of ustekinumab through 5 years in the PHOENIX 1 study.

METHODS: Patients were randomized to placebo or ustekinumab (45 mg or 90 mg) at Weeks 0, 4 and every-12-weeks thereafter; placebo patients crossed-over to ustekinumab at Week 12. Clinical response through Week 244 was evaluated using the Psoriasis Area and Severity Index (PASI) in the Overall Population (i.e. patients receiving ≥ 1 dose of ustekinumab), Initial Responders (i.e. PASI 75 responders [Weeks 28/40] re-randomized at Week 40 to continue every-12-week maintenance) and Partial Responders (i.e. <PASI 75 responders adjusted to every-8-week maintenance at Weeks 28 or 40). Safety endpoints were evaluated through Week 264 for the Overall Population.

RESULTS: Overall, 68.7% (517/753) of ustekinumab-treated patients completed treatment through Week 244. Initial clinical responses were generally maintained through Week 244 (PASI 75: 63.4% and 72.0%; PASI 90: 39.7% and 49.0%; PASI 100: 21.6% and 26.4%) for patients receiving 45 mg and 90 mg, respectively. Similarly, PASI 75 responses were generally maintained among Initial Responders [79.1% (45 mg) and 80.8% (90 mg)] and Partial Responders [57.6% (45 mg) and 55.1% (90 mg)]. With 3104 patient-years of follow-up, rates of overall adverse events (AEs), serious AEs, serious infections, malignancies and major adverse cardiovascular events were generally consistent over time and comparable between doses.

CONCLUSIONS: Through 5 years of continuous treatment, ustekinumab demonstrated stable clinical response and a safety profile consistent with previous reports.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disorder that is associated with obesity. Independently, both psoriasis and obesity likely impose impressive physical and psychosocial burdens on affected patients.

OBJECTIVE: The purpose of this study was to evaluate the relative impact of body mass index (BMI) on the socioeconomic status, medical co-morbidities, and current and chronic quality of life of psoriasis patients.

METHODS: Overall, 114 subjects were examined and asked to complete a self-administered questionnaire regarding disabilities, relationships, education, as well as medical and economic outcomes. Participants also answered the ten questions used in the Dermatology Life Quality Index modified to ask 'over the last week', 'over the last year' and 'over your lifetime with psoriasis'. Survey responses were compared amongst the three patient groups based on BMI (normal, overweight, obese).

RESULTS: Patients with elevated BMI were more likely to rate their general health lower (P < 0.001), believe that psoriasis caused their weight gain (P = 0.014), experience sleep problems over their lifetime (P = 0.016), hide their psoriasis over their lifetime (P = 0.010), have their self-confidence affected by their psoriasis over their lifetime (P = 0.011) and avoid common activities over their lifetime (P = 0.012).

CONCLUSION: There are long-term negative effects of elevated BMI that impose additional burdens on psoriasis patients, including impairments in sleep quality and increased social anxiety.

BACKGROUND: Multiple metrics evaluate the efficacy of psoriasis treatment, but interestingly, the correlation between the mostly widely used clinical trial efficacy end point, the physician-rendered Psoriasis Area Severity Index PASI score and, the most widely used quality of life metric, the Dermatology Life Quality Index DLQI, is not always high.

OBJECTIVE: To perform a systematic review to determine PASI to DLQI correlation.

METHODS: RCTs of biological agents for the treatment of moderate-to-severe psoriasis were reviewed in accordance with PRISMA guidelines. The mean percentage PASI improvement and change in mean DLQI values were recorded and compared for treatment groups from baseline to 10-16 weeks of therapy.

RESULTS: A search of the literature yielded 155 sources, of which 13 RCTs met inclusion and exclusion criteria. Percentage of PASI improvement from baseline correlates with DLQI changes with an r(2) value of 0.80 from baseline through weeks 10-16. When grouped by mean percentage reduction in PASI, agents demonstrating >75% mean reduction in PASI demonstrated a mean DLQI improvement over agents that achieved <75%-50% mean reduction in PASI or <50% mean reduction in PASI [minimal clinically important difference (MCID) 3.2]. In addition, a reduction in mean PASI of at least 75%, predicted a mean movement from DLQI band 3 to DLQI band 1, in all nine treatment arms demonstrating such efficacy.

CONCLUSIONS: Mean PASI and DLQI correlate predictably in patients with chronic moderate-to-severe plaque psoriasis undergoing treatment with biological agents. A reduction in PASI of at least 75% can translate to significant quality-of-life improvement in patients treated with these therapies.

BACKGROUND: Rates of malignancies and hospitalized infectious events (HIEs) among psoriasis patients are higher than in the general population, but it is unclear if higher rates are associated with the underlying inflammatory state, treatments or both.

OBJECTIVES: To assess the incidence of malignancies and HIEs in a healthy US population, a psoriasis population, and four treated psoriasis populations.

METHODS: Using a US claims database, we identified a general population, a psoriasis cohort, and four treatment cohorts [non-biologic systemics, etanercept, other TNF blockers (adalimumab, infliximab) and phototherapy] to assess the incidence of lymphomas, nonmelanoma skin cancer (NMSC), all malignancies (excluding NMSC), and HIEs, standardized for age and sex.

RESULTS: Among 40 987 patients with psoriasis, 11% were prescribed non-biologics, 15% etanercept, 6% other TNF blockers and 11% phototherapy. For all cancers, the psoriasis population rate (114/10 000 person-years) was 20% greater than the rate found in the general population (95/10 000 person-years). For NMSC, the psoriasis population rate (129/10 000 person-years) was 65% greater than the general population rate (78/10 000 person-years). The incidence rate for each treatment modality was lower than the overall psoriasis cohort, except for phototherapy. There was little difference in the rates of lymphomas. NMSC rates were higher among patients treated with phototherapy. HIE rates ranged from 165/10 000 person-years for the phototherapy group to 262/10 000 person-years for the other anti-TNF group.

CONCLUSIONS: Patients with psoriasis appear to have higher rates of malignancy and HIE than the general population, with little difference in rates between the treatment methods, except for a higher rate of cancer among those receiving phototherapy.

BACKGROUND: Psoriasis symptoms have a significant negative impact on health-related quality of life, impairing physical functioning and well-being.

OBJECTIVE: To evaluate the impact of brodalumab, a human anti-interleukin-17R monoclonal antibody, on psoriasis symptom severity as measured by a novel patient-reported outcome measure, the Psoriasis Symptom Inventory, and dermatology-specific health-related quality of life as measured by the Dermatology Life Quality Index (DLQI).

METHODS: This was a secondary analysis of a phase II, randomized, double-blind, placebo-controlled clinical study of patients with moderate-to-severe psoriasis (n = 198) treated with brodalumab or placebo. This analysis assessed Psoriasis Symptom Inventory scores and DLQI scores over time. Analyses were conducted on all patients who were randomized and received one or more injections of the study drug according to intention to treat using last observation carried forward to impute missing data.

RESULTS: At week 12, subjects in the brodalumab groups had significant improvements in mean Psoriasis Symptom Inventory total scores [8.5 (70 mg), 15.8 (140 mg), 16.2 (210 mg) and 12.7 (280 mg)] compared with placebo (4.8). Mean improvements in DLQI were clinically meaningful (≥ 5.7) in the brodalumab groups (6.2, 9.1, 9.6 and 7.1, respectively) and significantly greater than placebo (3.1). Improvements in Psoriasis Symptom Inventory were observed as early as week 2 and in DLQI by week 4. All eight Psoriasis Symptom Inventory item scores improved significantly among the brodalumab groups by week 12.

CONCLUSIONS: Results were from a single randomized clinical trial and may not generalize to broader patient populations. However, treatment with brodalumab provided significant improvement in psoriasis symptoms in patients with moderate-to-severe psoriasis.

BACKGROUND: Psoriasis is associated with several comorbidities and behavioural risk factors.

OBJECTIVES: To evaluate demographic and disease characteristics in patients enrolled in the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

METHODS: PSOLAR is a global, prospective, longitudinal, disease-based registry that includes a postmarketing commitment to evaluate safety in patients with psoriasis. Enrolled patients had to be receiving, or be eligible to receive, conventional systemic or biological agents. Demographic/disease characteristics, medical histories, lifestyle risk factors and previous treatments are collected at enrolment. Efficacy and safety data are collected every 6 months for 8 years, and data are extracted annually. Selected parameters are evaluated by age quartile using post hoc analyses.

RESULTS: As of 23 August 2012, 11 900 patients were enrolled at 301 sites in North America, Europe and Latin America. Over half of the PSOLAR population (54·7%) is male, with a mean age of 48·6 years and mean body mass index of 30·9 kg m(-2) at enrolment. Mean duration of disease at enrolment was 17·5 years, and mean Physician's Global Assessment score was 2·0. Psoriatic arthritis (35·5%) and cardiovascular diseases (38·2%) were highly prevalent. Diabetes mellitus type II was reported in 11·4% of patients. Depression and anxiety were noted in 14·7% and 11·1% of patients, respectively; 79·0% reported any alcohol use and 56·7% reported smoking or a history of smoking. The occurrence of most comorbidities, including cardiovascular disease and risk factors, increased with age.

CONCLUSIONS: In the PSOLAR population, multiple and age-appropriate comorbidities are associated with psoriasis and may affect the selection of psoriasis treatments.

BACKGROUND: In patients with moderate-to-severe psoriasis, health-related quality of life (HRQOL) has been shown to improve in parallel with improvement in disease severity.

OBJECTIVES: To evaluate the role of pruritus (itch) in mediating the relationship between improvements in disease severity and HRQOL.

METHODS: Data from a phase 2 clinical trial, in which 142 patients with moderate-to-severe plaque psoriasis received ixekizumab or placebo, were used for this posthoc analysis. Relationships between improvement in Psoriasis Area and Severity Index (PASI), Itch Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI), as well as in individual DLQI domains (symptoms and feelings, treatment, work and school, daily activities, leisure, and personal relationships) from baseline to week 16 were determined. Multiple hierarchical linear regressions and Sobel tests were conducted to evaluate the results.

RESULTS: Improvement in PASI was highly correlated with pruritus improvement and improvements in DLQI total and domain scores at week 16 (P < 0·01). Multiple hierarchical linear regression analyses showed a statistically significant (P < 0·01) association between improvement in pruritus and improvement in DLQI total score and each of the six DLQI domain scores after adjusting for improvement in PASI. Sobel tests indicated that pruritus had a significant mediation effect (P < 0·05) on the association of PASI improvement with improvement in DLQI total score and all domains except the personal relationships score.

CONCLUSIONS: Pruritus appears to be an important mediator of the association between improvements in disease severity and HRQOL in patients with moderate-to-severe psoriasis.

The International Psoriasis Council, a global nonprofit organization dedicated to advancing psoriasis research and treatment, led an initiative to better define the association of various cardiometabolic comorbidities with psoriasis. In November 2013, a workshop was held in Boston, Mass. By assembling a panel of global dermatology, immunology, and cardiovascular experts, the objective was to better define the current status of the science that explains the association of psoriasis with various cardiometabolic-related comorbidities. The International Psoriasis Council has played a historical role in associating psoriasis with various comorbidities by integrating multidisciplinary expertise to advance the scientific and clinical knowledge through publications and clinical trials. This report synthesizes the current understanding of psoriasis with various cardiometabolic risk factors by exploring the potential shared pathogenic mechanisms and genetic connectivity.

BACKGROUND: OBSERVE-5 was a 5-year Food and Drug Administration-mandated surveillance registry of patients with psoriasis.

OBJECTIVE: We sought to assess long-term etanercept safety and effectiveness.

METHODS: Patients with moderate to severe psoriasis enrolled; a single baseline dose of etanercept was required. Key outcome measures included serious adverse events, serious infectious events, events of medical interest, psoriasis-affected body surface area, physician global assessment score, and Dermatology Life Quality Index score. Safety outcomes were assessed relative to data from the MarketScan database.

RESULTS: For 2510 patients, 5-year cumulative incidence was 22.2% (95% confidence interval [CI] 20.3%-24.2%) for serious adverse events; 6.5% (95% CI 5.4%-7.7%) for serious infectious events; 3.2% (95% CI 2.3%-4.1%) for malignancies excluding nonmelanoma skin cancer; 3.6% (95% CI 2.7%-4.5%) for nonmelanoma skin cancer; 2.8% (95% CI 2.0%-3.6%) for coronary artery disease; 0.7% (95% CI 0.3%-1.2%) for psoriasis worsening; 0.2% (95% CI 0.0%-0.4%) for central nervous system demyelinating disorder; 0.1% (95% CI 0.0%-0.3%) for lymphoma and for tuberculosis; and 0.1% (95% CI 0.0%-0.2%) for opportunistic infection and for lupus; 55 fatal events were reported. Rates of malignancies, lymphomas, nonmelanoma skin cancer, and hospitalization-associated infections were not higher than expected relative to administrative claims data. The percentage of patients rated as clear/almost clear was 12% at baseline, which increased to 51% at month 6 and remained relatively stable throughout 5 years.

LIMITATIONS: No internal comparator group was included; rare events may not have been detected.

CONCLUSION: No new safety signals were observed with long-term, real-world etanercept use.

Psoriasis is associated with significant physical, social, and behavioral comorbidities that create a substantial burden. We outline herein that these comorbidities start early in life and persist for decades, ultimately impacting the entire life course of patients with psoriasis. By highlighting the ages that psoriasis patients are affected with physical, social, behavioral and emotional comorbidities, we demonstrate the age-appropriate considerations for psoriasis patients.

BACKGROUND: Psoriasis is a chronic skin disorder that detracts from quality of life, including elements of physical, psychological and social functioning.

OBJECTIVE: This study investigated whether retrospective questions about chronic quality of life (CQoL) were better predictors of poor socioeconomic and medical outcomes than the current Dermatology Life Quality Index (DLQI).

METHODS: One hundred fourteen participants answered the 10 questions used in the standard DLQI for 'over the last week', 'over the last year' and 'over your lifetime with psoriasis'. Subjects were examined and completed a self-administered questionnaire regarding disabilities, relationships, education and medical and economic outcomes (a smaller subset of 58 subjects also answered questions regarding religion and discrimination).

RESULTS: Greater lifetime DLQI (LT DLQI) correlated with lower satisfaction with treatment (P = 0.007), greater concern that psoriasis will worsen (P = 0.012), worse perceived general health (P = 0.003), younger age at which weight became problematic (P = 0.002), greater likelihood of believing psoriasis had caused weight gain (P < 0.001), shorter retention of current job (P = 0.001), more experiences of discrimination at work (P = 0.002) and in social settings (P < 0.001) over one's lifetime and more severe discrimination in social settings over one's lifetime (P = 0.002). Greater LT DLQI predicted more packs smoked per day (P = 0.005), greater likelihood of believing psoriasis caused smoking (P = 0.012), greater likelihood of recreational drug use (P = 0.004), greater likelihood of a depression diagnosis (P < 0.001), greater likelihood of having felt depressed (P = 0.011) and greater likelihood of believing psoriasis caused depression (P < 0.001).

CONCLUSION: Compared to the standard LW DLQI, LT DLQI was a better predictor of patient outcomes related to weight, discrimination and depression.