Reduced risk of mortality associated with systemic psoriasis treatment in the Psoriasis Longitudinal Assessment and Registry (PSOLAR): A nested case-control analysis.

BACKGROUND: The effects of systemic therapy on mortality risk among patients with psoriasis are not fully understood. OBJECTIVE: To evaluate the impact of systemic treatment on mortality risk in patients enrolled in the Psoriasis Longitudinal Assessment and Registry. METHODS: Nested case-control analyses were performed to estimate mortality risk. Cases were defined as patients who died while participating in the Psoriasis Longitudinal Assessment and Registry. Cases were matched (1:4) with controls by age, race, sex, and geographic region. Evaluated treatments included methotrexate, ustekinumab, and tumor necrosis factor α inhibitors. Exposure was defined as at least 1 dose of treatment within 3 months before death and was stratified by duration of therapy. RESULTS: Among 12,090 patients, 341 deaths occurred, matched to 1364 controls. Biologic treatment within the preceding 3 months was protective against mortality versus no exposure: odds ratio (OR) for exposure of less than 1 year, 0.08 (95% confidence interval [CI], 0.03-0.23); OR for exposure of 1 year or longer, 0.09 (95% CI, 0.06-0.13). Methotrexate was protective against mortality only with exposure for 1 year or longer (OR, 0.08; 95% CI, 0.02-0.28). LIMITATIONS: Observational studies are subject to unmeasured confounding. CONCLUSIONS: Biologic therapy was associated with reduced mortality risk in patients with moderate to severe psoriasis, regardless of treatment duration; methotrexate reduced risk only with exposure for 1 year or longer.

Real-World Experience With Apremilast in the Treatment of Adults With Moderate to Severe Plaque Psoriasis in Québec: A Claims-Based Analysis of Drug Utilization and Healthcare Resource Utilization.

BACKGROUND: In Québec, targeted biologic therapies for moderate to severe plaque psoriasis are restricted to patients who have not responded to phototherapy or conventional systemic treatment, primarily due to high drug costs. Apremilast, an oral treatment for plaque psoriasis, was added to the Québec provincial health insurance plan (Régie de l'assurance maladie du Québec; RAMQ) formulary in 2015, making this the only province in Canada with public drug plan reimbursement for apremilast. OBJECTIVES: The aim of this study is to describe patients' characteristics, treatment patterns, healthcare resource utilization (HCRU), and associated costs and to measure real-world budget impact of using apremilast before biologics in plaque psoriasis. METHODS: This study was performed using RAMQ drug claims and medical services data. Patients diagnosed with psoriasis between January 2015 and December 2017 were identified. Medical services and prescription claims were categorized as all-cause and psoriasis-related. Using RAMQ database estimates, a 3-year budget impact analysis was developed comparing treatment cost with and without the addition of apremilast to the formulary. RESULTS: In all, 540 patients were identified (apremilast: n = 92; biologics: n = 448). Comorbidity burden and treatment persistence and adherence were comparable between apremilast and biologic users. The year following the index date, all-cause HCRU was lower for apremilast versus biologic users (CAN$19 763 vs CAN$28 025; P < .01), mainly driven by drug cost. Using apremilast before biologics resulted in an estimated RAMQ net savings of CAN$49 290 (2015), CAN$746 856 (2016), and CAN$1 216 512 (2017), and a total savings of CAN$2 012 658 since apremilast's addition to the formulary. CONCLUSION: Adding apremilast to the drug formulary of other Canadian provinces could result in significant healthcare savings.

Serious infections in patients with self-reported psoriatic arthritis from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) treated with biologics.

BACKGROUND: Patients with psoriatic arthritis (PsA) have increased risk of adverse events, including serious infections (SI), compared with psoriasis patients. METHODS: Patients eligible for, or receiving conventional systemic and biologic agents for psoriasis were followed prospectively using PSOLAR. Cohorts included: ustekinumab, tumor necrosis factor (TNF) inhibitors; infliximab; etanercept; adalimumab; non-biologic/methotrexate (MTX) (reference group); and non-biologic/non-MTX. Multivariate analyses using Cox hazard regression were used to identify factors associated with time to first SI. Rates of SI in PSOLAR psoriasis patients with self-reported PsA and possible risks with biologic therapy were evaluated. RESULTS: PSOLAR enrolled 4315 psoriasis patients with self-reported PsA. The overall population (N = 2401) included patients (n): 628 ustekinumab; 1413 TNF inhibitors; 258 infliximab; 481 etanercept; 674 adalimumab; 54 other biologics, 98 non-biologic/MTX; 208 non-biologic/non-MTX. Overall, 138 SI were reported with incidence rates per 100 patient-years as follows: a) ustekinumab: 1.00; b) TNF inhibitors: 2.22; c) infliximab: 2.12; d) etanercept: 2.58; e) adalimumab: 1.99; f) non-biologic/MTX: 3.01; g) and non-biologic/non-MTX: 2.31. Age, time-dependent disease activity Physician's Global Assessment (PGA) of 4, 5, history of infection, and diabetes were associated with increased risk for SI (p < 0.05) in self-reported PsA patients. Biologic groups, other than ustekinumab, had numerically higher rates of SI. CONCLUSIONS: PSOLAR psoriasis patients with self-reported PsA in the TNF inhibitors, infliximab, adalimumab, etanercept, and MTX cohorts had numerically higher SI rates than the ustekinumab cohort, although not statistically significant. Age, PGA 4, 5, history of infection, and diabetes were associated with an increased risk for SI, irrespective of biologic exposure. TRIAL REGISTRATION: NCT00508547; Registered July 30, 2007.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document.

BACKGROUND:: Atopic dermatitis (AD) is a chronic, relapsing, and remitting inflammatory skin disease with complex pathophysiology, primarily driven by type 2 inflammation. Existing guidelines often do not reflect all current therapeutic options and guidance on the practical management of patients with AD is lacking. OBJECTIVES:: To develop practical, up-to-date guidance on the assessment and management of adult patients with AD. METHODS:: An expert panel of 17 Canadian experts, including 16 dermatologists and 1 allergist, with extensive clinical experience managing moderate-to-severe AD reviewed the available literature from the past 5 years using a defined list of key search terms. This literature, along with clinical expertise and opinion, was used to draft concise, clinically relevant reviews of the current literature. Based on these reviews, experts developed and voted on recommendations and statements to reflect the practical management of adult patients with AD as a guide for health care providers in Canada and across the globe, using a prespecified agreement cutoff of 75%. RESULTS:: Eleven consensus statements were approved by the expert panel and reflected 4 key domains: pathophysiology, assessment, comorbidities, and treatment. CONCLUSIONS:: These statements aim to provide a framework for the assessment and management of adult patients with AD and to guide health care providers in practically relevant aspects of patient management.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section V: Consensus Statements on the Assessment and Management of Adult Patients With Moderate-to-Severe Atopic Dermatitis.

This document is a concise, current, and practical guide for dermatologists and other health care providers managing adult patients with moderate-to-severe atopic dermatitis (AD). The recommendations made here are based on a consensus of specialists with extensive experience managing patients with AD. Topics reviewed in this publication include AD pathophysiology, assessment, comorbidities, and treatment options.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section IV: Treatment Options for the Management of Atopic Dermatitis.

The objectives of therapy for atopic dermatitis (AD) are to reduce skin inflammation and pruritus, restore skin barrier function, and improve quality of life (QoL). Treatments can be classified as moisturizing and basic care, topical therapy, phototherapy, and systemic therapy. In this review, we summarize the treatments for AD and recommendations for their use.

Canadian Clinical Practice Guidelines for Rosacea.

Rosacea is a chronic facial inflammatory dermatosis characterized by background facial erythema and flushing and may be accompanied by inflammatory papules and pustules, cutaneous fibrosis and hyperplasia known as phyma, and ocular involvement. These features can have adverse impact on quality of life, and ocular involvement can lead to visual dysfunction. The past decade has witnessed increased research into pathogenic pathways involved in rosacea and the introduction of novel treatment innovations. The objective of these guidelines is to offer evidence-based recommendations to assist Canadian health care providers in the diagnosis and management of rosacea. These guidelines were developed by an expert panel of Canadian dermatologists taking into consideration the balance of desirable and undesirable outcomes, the quality of supporting evidence, the values and preferences of patients, and the costs of treatment. The 2015 Cochrane review "Interventions in Rosacea" was used as a source of clinical trial evidence on which to base the recommendations.

Risk of Serious Infection With Biologic and Systemic Treatment of Psoriasis: Results From the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

IMPORTANCE: The efficacy of treatment for psoriasis must be balanced against potential adverse events. OBJECTIVE: To determine the effect of treatment on the risk of serious infections in patients with psoriasis. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, longitudinal, disease-based registry (Psoriasis Longitudinal Assessment and Registry [PSOLAR]) at dermatology centers. Participants were adult patients with psoriasis who were receiving or were eligible to receive conventional systemic or biologic agents. The registry opened on June 20, 2007, and data included herein were collected through August 23, 2013. EXPOSURES: Patients were prescribed psoriasis therapies as in standard clinical practice. Patients will be followed for up to 8 years. Data were collected and serious adverse events (including serious infections) were assessed at regular intervals. MAIN OUTCOMES AND MEASURES: Cohort characteristics are described based on evaluation at entry into the registry. The cumulative incidence rates of serious infections are reported across treatment cohorts, including ustekinumab, infliximab, adalimumab, etanercept, and nonbiologics (with or without methotrexate). A multivariate analysis using a Cox proportional hazards regression model was used to identify predictors of the time to the first serious infection using the nonmethotrexate/nonbiologics cohort as the reference. RESULTS: Data were analyzed from 11,466 patients with psoriasis (22,311 patient-years). Differences in patient characteristics were found between the biologics and nonmethotrexate/nonbiologics cohorts (eg, age, sex, body mass index, and disease characteristics), as well as among the individual biologic groups (eg, a higher prevalence of psoriatic arthritis in the infliximab cohort). The cumulative incidence rate of serious infections was 1.45 per 100 patient-years (n = 323) across treatment cohorts, and the rates were 0.83, 1.47, 1.97, and 2.49 per 100 patient-years in the ustekinumab, etanercept, adalimumab, and infliximab cohorts, respectively, and 1.05 and 1.28 per 100 patient-years in the nonmethotrexate/nonbiologics and methotrexate/nonbiologics cohorts, respectively. The most commonly reported types of serious infections across the registry were pneumonia and cellulitis. Increasing age, diabetes mellitus, smoking, significant infection history, infliximab exposure, and adalimumab exposure were each associated with an increased risk of serious infection. CONCLUSIONS AND RELEVANCE: Results from PSOLAR suggest a higher risk of serious infections with adalimumab and infliximab compared with nonmethotrexate and nonbiologic therapies. No increased risk was observed with ustekinumab or etanercept. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00508547.

Psychometric properties of the French Female Sexual Function Index (FSFI).

INTRODUCTION: Few validated questionnaires are available in French to assess sexual function. The aim of this study was thus to validate a French version of the Female Sexual Function Index (FSFI) in a sample of French women. METHODS: In this prospective monocentric and cross-sectional study, an already existing French version of the FSFI, was back-translated and compared to the original version. It was then randomly distributed to 800 women attending Gynecology consultation at Nantes University Hospital in April 2012. Various statistical analyzes were used to test the psychometric properties of the French FSFI. RESULTS: 512 questionnaires were completed. Mean FSFI summary score was 25.2. Intraclass correlation coefficients were superior to 0.75 and Cronbach's coefficients superior to 0.8 similarly to the original version. Variance analysis revealed significant differences in summary score between premenopausal and postmenopausal women and according to the marital status. Convergent validity was excellent (100%) and discriminant validity was satisfactory (89.5%). The factorial structure corresponded to the original version with six retrieved dimensions. CONCLUSIONS: Our study demonstrated similar or adequate psychometric properties of the French version of the FSFI compared to the original English version.

Assessment of the long-term safety and effectiveness of etanercept for the treatment of psoriasis in an adult population.

BACKGROUND: Etanercept is well tolerated and effective in moderate to severe plaque psoriasis. However, effectiveness and safety data beyond 2.5 years have not been reported. OBJECTIVE: We sought to assess the effectiveness and safety profile of up to 4 years of etanercept therapy in psoriasis. METHODS: We analyzed prospective data from previous trials and open-label extensions, including 506 patients who initiated etanercept therapy in either of two phase III trials. Patients received etanercept, 25 mg twice weekly, 50 mg weekly, or 50 mg twice weekly, depending on which trial therapy was started. Dosage adjustments were allowed in open-label extensions, but no patients exceeded 50 mg twice weekly. Outcomes included change from baseline for the static Physician Global Assessment and Dermatology Life Quality Index scores. Exposure-adjusted adverse event (AE) rates were calculated. RESULTS: In all, 75.9% (95% confidence interval 67.9-84.0) and 27.8% (95% confidence interval 19.3-36.2) maintained Dermatology Life Quality Index response (≥ 5-point improvement from baseline) and static Physician Global Assessment response (clear or almost clear) at 48 months, respectively. AE and serious AE rates were 243.5 and 7.8 events per 100 patient-years, respectively. No serious AE rates exceeded 1.0 event per 100 patient-years. Overall infection and serious infection rates were 96.9 and 0.9 events per 100 patient-years, respectively. No cases of tuberculosis or lymphoma were reported. LIMITATIONS: Effectiveness data were limited to static Physician Global Assessment and Dermatology Life Quality Index scores. Analysis of AE rates was limited to available comparator databases. CONCLUSION: Etanercept demonstrated sustained effectiveness and a favorable safety profile with no cumulative toxicity for up to 4 years, representing, to our knowledge, the longest published study on etanercept use in psoriasis to date.

Canadian hand dermatitis management guidelines.

BACKGROUND: Hand dermatitis (HD) is one of the most common skin conditions; however, it is not a homogeneous disease entity. The severity of HD may range from very mild cases to severe chronic forms, which may result in prolonged disability and, occasionally, refractory HD. Chronic hand dermatitis (CHD) is associated with a high health- economic burden and significant loss of quality of life. OBJECTIVE: Although numerous treatment options are available, the management of CHD is often difficult and unsatisfactory. There is a paucity of well-designed, randomized, controlled clinical trials in support of the efficacy of established treatment modalities. CONCLUSION: These guidelines cover the epidemiology, burden, quality of life, etiology, diagnosis, classification, and prevention of HD and provide guidance on management using an approach that is as evidence based as possible.

Epidemiology of moderate-to-severe plaque psoriasis in a Canadian surveyed population.

BACKGROUND: limited data are available on the epidemiologic features of psoriasis in Canada. OBJECTIVE: to investigate the epidemiologic features and burden of moderate-to-severe psoriasis in a Canadian population. METHODS: an online survey was conducted using a consumer panel. Eligible respondents indicated a diagnosis of psoriasis and plaque-type psoriasis of at least moderate severity. Eligibility was validated according to self-reported body surface area (BSA) involvement, sensitive areas affected, and/or current treatment. RESULTS: of the 514 respondents who completed the survey, 62% estimated a BSA involvement of >/= 3% within the past 5 years. Onset of psoriasis occurred earlier in females than in males. Nail involvement was more commonly reported in individuals with psoriatic arthritis compared to those without. Several symptoms were more likely described as "constantly" or "near constantly" experienced by females than by males. Comorbidities commonly reported were hypertension, dyslipidemia, and overweight or obesity. CONCLUSIONS: the findings are consistent with a substantial burden attributed to moderate-to-severe plaque psoriasis in a Canadian population.

Biologics in the treatment of psoriasis: clinical and economic overview.

BACKGROUND: The use of biologic medications for psoriasis is a recent therapeutic advance. OBJECTIVE: To review clinical and economic data for biologic therapies in the treatment of chronic plaque psoriasis. METHODS: Published meta-analyses and additional literature review identified randomized controlled trials. Analyses included the number needed to treat (NNT), the cost in Canadian dollars for the first year of treatment per the Canadian product monograph, and the estimated cost per responder achieving a 75% reduction in Psoriasis Area and Severity Index score (PASI 75). RESULTS: Pooled NNTs were 1.3 (infliximab), 1.5 (ustekinumab 90 mg), 1.6 (adalimumab and ustekinumab 45 mg), 2.3 (etanercept), 4.1 (efalizumab), and 5.6 (alefacept). The annual treatment cost per patient was $19,825 to $37,600. The cost per patient achieving a PASI 75 response at 12 weeks ranged from $8,330 (adalimumab) to $71,371 (alefacept). CONCLUSION: This analysis suggests favorable cost and benefits of biologic psoriasis therapies, particularly adalimumab, infliximab, and ustekinumab.

Practical aspects of prescribing a biologic.

As the use of biologic agents for treatment of psoriasis becomes more common, practitioners need to be aware of the unique concerns and procedures required when prescribing biologics. This article describes the clinical and laboratory assessments that should occur before starting a biologic treatment, as well as the contraindications to consider for patients who might be candidates for biologic treatment. Important-treatment monitoring issues for safe and effective use of biologics in patients with psoriasis are also discussed.

Work-related lost productivity and its economic impact on Canadian patients with moderate to severe psoriasis.

BACKGROUND: Psoriasis impacts many different areas of a patient's life, including work productivity. There is no information regarding lost productivity owing to psoriasis in a Canadian population. OBJECTIVE: The objective of this study was to determine the lost productivity of Canadian patients with moderate to severe psoriasis. METHODS: Seventy-nine consecutive Canadian dermatology patients were interviewed and completed the Work Productivity and Activity Impairment Questionnaire (WPAIQ). RESULTS: On average, 2.2 hours (+/- 5.6 hours) were lost from work per week owing to psoriasis-related events. Absence from work may result in lost mean patient wages of C$2,270.84 per person per year. Total lost wages owing to moderate to severe psoriasis may cost up to approximately $749 million for all moderate to severe psoriasis patients in Canada. CONCLUSION: The results from our study indicate that moderate to severe psoriasis may have a substantial impact on the work productivity of patients with this disease.

A multicenter, double-blind, randomized comparison study of the efficacy and tolerability of once-daily tazarotene 0.1% gel and adapalene 0.1% gel for the treatment of facial acne vulgaris.

The efficacy and tolerability of tazarotene 0.1% gel and adapalene 0.1% gel were compared in a multicenter, double-blind, randomized, parallel-group study in 145 patients with mild-to-moderate facial acne vulgaris. Both treatments were applied once daily in the evenings for up to 12 weeks. Compared with adapalene, treatment with tazarotene was associated with a significantly greater incidence of treatment success (> or = 50% global improvement) (78% vs 52%; P=.002) and significantly greater reductions in overall disease severity (P<.0001), noninflammatory lesion count (P<.0001), and inflammatory lesion count (P=.0002). In the early weeks of treatment, tazarotene was associated with transiently greater levels of burning, pruritus, erythema, and peeling compared with adapalene (P<.01). However, mean levels of these parameters were consistently less than mild in both treatment groups and, at the end of treatment, patients considered both treatments to be comparably well tolerated (the proportion of patients in each group who rated the comfort of their treated skin as comfortable or very comfortable was 76% with tazarotene and 69% with adapalene). Mean usage of study medication was 0.32 g per application of tazarotene and 0.42 g per application of adapalene, which resulted in cost-effectiveness ratios of $79.95 per treatment success for tazarotene and $107.88 per treatment success for adapalene. Sensitivity analyses suggest that these cost-effectiveness results are robust across a range of cost and efficacy assumptions. In conclusion, tazarotene 0.1% gel was more effective than adapalene 0.1% gel and was also a more cost-effective treatment option.