Long-term safety and effectiveness of roflumilast cream 0.3% in adults with chronic plaque psoriasis: A 52-week, phase 2, open-label trial.

BACKGROUND: Efficacy and/or safety profiles limit topical psoriasis treatments. OBJECTIVE: Evaluate long-term effects of once-daily roflumilast cream 0.3% in patients with psoriasis. METHODS: In this open-label phase 2 trial, adult patients (N = 332) with psoriasis who completed the phase 2b parent trial or were newly enrolled applied roflumilast once-daily for 52 weeks. Safety and effectiveness were assessed. RESULTS: Overall, 244 patients (73.5%) completed the trial; 13 patients (3.9%) discontinued due to adverse events (AEs) and 3 (0.9%) due to lack of efficacy. Twelve patients (3.6%) reported treatment-related AEs; none were serious. ≥97% of patients had no irritation. No tachyphylaxis was observed with 44.8% of the patients achieving Investigator Global Assessment (IGA) Clear or Almost Clear at Week 52. LIMITATIONS: Intertriginous-IGA and Psoriasis Area and Severity Index (PASI) were not evaluated in all patients. CONCLUSIONS: In this long-term trial, once-daily roflumilast cream was well-tolerated and efficacious up to 64 weeks in patients in the earlier trial, suggesting it is suitable for chronic treatment, including the face and intertriginous areas.

Efficacy and safety of apremilast in patients with mild-to-moderate plaque psoriasis: Results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Patients with mild-to-moderate psoriasis may have substantial quality-of-life impairment. OBJECTIVE: To evaluate apremilast 30 mg twice daily for mild-to-moderate psoriasis. METHODS: Phase 3, double-blind, placebo-controlled study in adults with mild-to-moderate psoriasis inadequately controlled or intolerant to ≥ 1 topical psoriasis therapy (NCT03721172). The primary endpoint was the achievement of static Physician Global Assessment score of 0 (clear) or 1 (almost clear) and ≥ 2-point reduction at week 16. RESULTS: Five hundred ninety-five patients were randomized (apremilast: 297; placebo: 298). The primary endpoint was met, with a significantly greater static Physician Global Assessment response rate observed at week 16 in the apremilast group compared with the placebo group (21.6% vs 4.1%; P < .0001). All secondary endpoints were met with the achievement of body surface area-75 (33.0% vs 7.4%), body surface area ≤ 3% (61.0% vs 22.9%), ≥ 4-point reduction in Whole Body Itch Numeric Rating Scale (43.2% vs 18.6%), Scalp Physician Global Assessment 0 or 1 and ≥ 2-point reduction (44.0% vs 16.6 %), and changes from baseline in body surface area, Psoriasis Area and Severity Index, and Dermatology Life Quality Index (all P < .0001). The most commonly reported adverse events (≥ 5%) with apremilast were diarrhea, headache, nausea, nasopharyngitis, and upper respiratory tract infection, consistent with prior studies. LIMITATIONS: The study lacked an active-comparator arm. CONCLUSION: Apremilast demonstrated efficacy in mild-to-moderate psoriasis and safety consistent with the established safety profile of apremilast.

Effect of Roflumilast Cream vs Vehicle Cream on Chronic Plaque Psoriasis: The DERMIS-1 and DERMIS-2 Randomized Clinical Trials.

Importance: Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis. Objective: To evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis. Design, Setting, and Participants: Two phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n = 439] and DERMIS-2 [trial 2; n = 442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between December 9, 2019, and November 23, 2020, respectively. Patients aged 2 years or older with plaque psoriasis involving 2% to 20% of body surface area were enrolled. The dates of final follow-up were November 20, 2020, and November 23, 2020, for trial 1 and trial 2, respectively. Interventions: Patients were randomized 2:1 to receive roflumilast cream, 0.3% (trial 1: n = 286; trial 2: n = 290), or vehicle cream (trial 1: n = 153; trial 2: n = 152) once daily for 8 weeks. Main Outcomes and Measures: The primary efficacy end point was Investigator Global Assessment (IGA) success (clear or almost clear status plus ≥2-grade improvement from baseline [score range, 0-4]) at week 8, analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA score, and intertriginous involvement. There were 9 secondary outcomes, including intertriginous IGA success, 75% reduction in Psoriasis Area and Severity Index (PASI) score, and Worst Itch Numeric Rating Scale score of 4 or higher at baseline achieving 4-point reduction (WI-NRS success) at week 8 (scale: 0 [no itch] to 10 [worst imaginable itch]; minimum clinically important difference, 4 points). Results: Among 881 participants (mean age, 47.5 years; 320 [36.3%] female), mean IGA scores in trial 1 were 2.9 [SD, 0.52] for roflumilast and 2.9 [SD, 0.45] for vehicle and in trial 2 were 2.9 [SD, 0.48] for roflumilast and 2.9 [SD, 0.47]) for vehicle. Statistically significantly greater percentages of roflumilast-treated patients than vehicle-treated patients had IGA success at week 8 (trial 1: 42.4% vs 6.1%; difference, 39.6% [95% CI, 32.3%-46.9%]; trial 2: 37.5% vs 6.9%; difference, 28.9% [95% CI, 20.8%-36.9%]; P < .001 for both). Of 9 secondary end points, statistically significant differences favoring roflumilast vs vehicle were observed for 8 in trial 1 and 9 in trial 2, including intertriginous IGA success (71.2% vs 13.8%; difference, 66.5% [95% CI, 47.1%-85.8%] and 68.1% vs 18.5%; difference, 51.6% [95% CI, 29.3%-73.8%]; P < .001 for both), 75% reduction in PASI score (41.6% vs 7.6%; difference, 36.1% [95% CI, 28.5%-43.8%] and 39.0% vs 5.3%; difference, 32.4% [95% CI, 24.9%-39.8%]; P < .001 for both), WI-NRS success (67.5% vs 26.8%; difference, 42.6% [95% CI, 31.3%-53.8%] and 69.4% vs 35.6%; difference, 30.2% [95% CI, 18.2%-42.2%]; P < .001 for both). The incidence of treatment-emergent adverse events was 25.2% with roflumilast vs 23.5% with vehicle in trial 1 and 25.9% with roflumilast vs 18.4% with vehicle in trial 2. The incidence of serious adverse events was 0.7% with roflumilast vs 0.7% with vehicle in trial 1 and 0% with roflumilast vs 0.7% with vehicle in trial 2. Conclusions and Relevance: Among patients with chronic plaque psoriasis, treatment with roflumilast cream, 0.3%, compared with vehicle cream resulted in better clinical status at 8 weeks. Further research is needed to assess efficacy compared with other active treatments and to assess longer-term efficacy and safety. Trial Registration: ClinicalTrials.gov Identifiers: NCT04211363, NCT04211389.

Dermatologists' Perspectives on Defining Moderate Psoriasis: The Canadian Moderate Psoriasis Survey.

BACKGROUND: Psoriasis is commonly classified as either mild or moderate to severe, without specific parameters to differentiate moderate versus severe disease. This may lead to patients with moderate psoriasis being underrecognized and undertreated. OBJECTIVE: An online survey was conducted to assess Canadian dermatologists’ perspectives on the definition and treatment of psoriasis. METHOD: Dermatologists included in the survey were regional and national leaders with expertise in psoriasis. Questions were developed based on feedback from a steering committee of Canadian dermatologists. RESULTS: Of 88 dermatologists contacted, 69 responded; 42.0% were in practice for >20 years. Most dermatologists reported using the percentage of psoriasis-affected body surface area (BSA) to describe disease severity (90.8% for moderate and 87.5% for severe psoriasis). The lower and upper median cutoffs for moderate psoriasis were reported as 5.0% and 10.0% for BSA and 7.0 and 11.5 for the Dermatology Life Quality Index. Most dermatologists also consider psoriasis location (eg, palms, scalp, genital area, face) as an important indicator of disease severity. The majority of Canadian dermatologists (87.5%) identified access to treatment as one of the biggest challenges for patients with moderate psoriasis. Most dermatologists estimated that ≤40% of their patients with moderate plaque psoriasis were being treated with traditional oral systemics, targeted oral systemics, or biologics. CONCLUSIONS: This is the first survey of Canadian dermatologists on moderate psoriasis. Efforts are needed to implement a clinically useful definition of moderate plaque psoriasis to improve patient care and to raise awareness of the definition among regulatory agencies and reimbursement authorities. J Drugs Dermatol. 2021;20(2):126-132. doi:10.36849/JDD.5531.

Efficacy and safety of ingenol mebutate gel in field treatment of actinic keratosis on full face, balding scalp, or approximately 250 cm2 on the chest: A phase 3 randomized controlled trial.

BACKGROUND: Ingenol mebutate (IngMeb) 0.015% or 0.05% is approved for actinic keratosis (AK) areas of 25 cm2 or less; some patients require treatment of larger fields. OBJECTIVE: To determine efficacy and safety of IngMeb 0.027% in areas of AK of up to 250 cm2 during an 8-week initial assessment period and extended 12-month follow-up. METHODS: This phase 3, randomized, double-blind, vehicle-controlled trial (NCT02361216) enrolled adult patients with 5 to 20 AK lesions on the face/scalp (25-250 cm2) or chest (approximately 250 cm2). Patients received once-daily IngMeb or vehicle for 3 consecutive days on the full face, full balding scalp, or approximately 250 cm2 on the chest. The primary endpoint was complete AK clearance (AKCLEAR 100; week 8). Additional endpoints included partial AK clearance (AKCLEAR 75), recurrence, patient satisfaction, cosmetic outcome, and safety. RESULTS: IngMeb was superior to vehicle for complete AK clearance (21.4% vs 3.4%, P < .001) and AK clearance of 75% or greater (59.4% vs 8.9%, P < .001) at week 8. Probability of sustained clearance during the 12-month follow-up was 22.9% for patients treated with IngMeb. Increased treatment satisfaction and cosmetic outcomes were observed with IngMeb versus vehicle. No unexpected safety signals were identified. LIMITATIONS: Localized skin responses hindered maintenance of double-blinding. CONCLUSIONS: IngMeb 0.027% was superior to vehicle for treatment of AK areas of up to 250 cm2. The safety profile of IngMeb was as expected.

Rationale, objectives and design of PURE, a prospective registry of patients with moderate to severe chronic plaque psoriasis in Canada and Latin America.

BACKGROUND: Treatment options for the management of moderate to severe plaque psoriasis include phototherapy, oral systemic agents, and biologic therapy. Secukinumab, a fully human monoclonal antibody that selectively targets IL-17A, is the first IL-17 antagonist approved for this patient population. Long-term observational data are required for establishing the true population-based benefit-risk ratio of approved treatments. PURE is a multinational registry that will assess the real-world safety and effectiveness of secukinumab and other approved therapies in the management of patients with moderate to severe psoriasis. METHODS: This is a multinational (Canadian and Latin American), prospective, observational study of adult patients with moderate to severe psoriasis that initiate treatment with secukinumab or other approved therapies as per local standard of care. A total of 2500 patients (1250 per cohort) will be recruited in the practices of hospital and community dermatologists. Decision regarding treatment must have been reached prior to and independent of patient enrollment in the study. The study includes a 5-year follow-up with recommended assessments at Baseline, 3 and 6 months post-Baseline, and every 6 months thereafter. The primary objective of the study is safety. Secondary outcome measures relate to effectiveness (Investigator's Global Assessment -IGA mod 2011-, Psoriasis Areas and Severity Index, Body Surface Area), patient reported outcomes (Dermatology Life Quality Index, Work Productivity and Activity Impairment Questionnaire, Hospital Anxiety and Depression Scale, Psoriasis Epidemiology Screening Tool, Psoriasis Symptom Diary, and Treatment Satisfaction Questionnaire), and healthcare resource utilization. DISCUSSION: This is the first observational study in Canada and Latin America assessing the real-world safety and effectiveness of secukinumab in the management of moderate to severe psoriasis. The extensive clinical, patient-reported and health economic outcomes collected will allow the comprehensive evaluation of this new treatment in comparison to other approved therapies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02786186 ; date of registration: May 30, 2016.

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.

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.

Canadian Expert Consensus on the Use of Halobetasol Propionate/Tazarotene Lotion for Plaque Psoriasis.

INTRODUCTION: An expert panel of Canadian dermatologists was assembled to develop consensus statements regarding the current landscape of topical therapies for plaque psoriasis and the place in therapy of the recently approved fixed-dose combination halobetasol propionate (HP)/tazarotene (TAZ) lotion (HP/TAZ) in the treatment algorithm for plaque psoriasis. METHOD: A modified nominal group technique, which combined both independent and group input from the expert panel, was used to develop the consensus statements. The expert panel completed surveys to elicit their independent views on the current landscape of topical therapies for plaque psoriasis in Canada. The first expert panel session was held to discuss the existing body of literature and develop draft consensus statements about topical therapies and the place in therapy of HP/TAZ. Independent feedback on the draft consensus statements was solicited from expert panel members prior to another expert panel session where the amended consensus statements were further discussed, edited and, finally, voted on. RESULTS: The expert panel reached consensus on 20 statements. CONCLUSION: Expert panel members agreed, based on the existing body of literature, that there is a place in therapy for HP/TAZ to address several current unmet treatment needs of patients with plaque psoriasis. Studies have shown that HP/TAZ is an effective and safe first-line treatment for moderate-to-severe plaque psoriasis. Due to its cosmetically pleasing vehicle and once-daily administration, HP/TAZ may improve patient acceptance and treatment adherence.

Effectiveness and safety of secukinumab updosing in patients with moderate to severe plaque psoriasis: data from the PURE registry.

Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin-17A. Secukinumab is an effective and well-tolerated treatment for plaque psoriasis. There is a limited real-word evidence for dose optimisation of secukinumab based on clinical response. PURE is a multi-national, prospective, observational study in patients with moderate to severe chronic plaque psoriasis in Canada and Latin America, assessing the real-world safety and effectiveness of secukinumab and other indicated therapies. The aim of the current snapshot analysis was to evaluate the effectiveness and safety of on-label dose and updosed secukinumab in patients with plaque psoriasis enrolled in the PURE study. At the time of analysis, 676 patients received secukinumab, of which 84.6% (n = 572) remained on the on-label dose, while 15.4% (n = 104) were updosed. With on-label secukinumab, the absolute Psoriasis Area and Severity Index (PASI) score was reduced from 13.6 at baseline to 1.2 over 36 months, with treatment persistence of 73% at 40 months. At Month 36, 73.2% of the patients receiving on-label secukinumab achieved Investigator's Global Assessment (IGA) 0/1. With updosed secukinumab (300 mg every 2 weeks, 300 mg every 3 weeks, 450 mg every 4 weeks, or 450 mg every 3 weeks), 57.9% of the patients showed improvement in the absolute PASI score at the first visit after updosing, with treatment persistence of 50% at 12 months after updosing. At Month 15, 40% of patients receiving updosed secukinumab achieved IGA 0/1. Patients with previous biologic exposure (odds ratio [OR]: 3.25; 95% confidence interval [CI]: 2.03, 5.18, p < 0.0001) were more likely to be updosed while those with a body weight < 90 kg (OR: 0.49; 95% CI [0.31, 0.77], p = 0.0019) were less likely to be updosed. Previous biologic exposure (HR [hazard ratio]: 1.47; 95% CI [1.24, 1.75], p < 0.0001) and current biologic exposure (secukinumab vs. other indicated therapies: HR 0.57; 95% CI [0.43, 0.75], p = 0.0001) were significantly associated with time to secukinumab updosing. No new or unexpected safety signals were observed with updosed secukinumab. Secukinumab updosing was efficacious and well-tolerated in patients with psoriasis who failed to respond to the approved on-label regimen, suggesting that updosing may be a useful therapeutic option for approved dose non-responders.

Sustained Effectiveness of Secukinumab Across Different Body Regions in Patients with Moderate-to-Severe Plaque Psoriasis from the PURE Registry.

INTRODUCTION: The association between physician-reported and patient-reported outcomes in patients with psoriasis is not adequately explored. Trends in PASI scores across body regions and the descriptive correspondence between physician-reported PASI components and patient-reported Psoriasis Symptom Diary are reported here. METHODS: PURE is a prospective observational study in adult patients from Canada and Latin America with moderate-to-severe chronic plaque psoriasis. The study enrolled 2362 adult patients treated with secukinumab versus other approved therapies (1:1 ratio). The PASI total score, PASI sub-scores for erythema, thickening, and scaling, and PASI scores for each body region were evaluated and further correlated with disease impact using the Psoriasis Symptom Diary. RESULTS: Secukinumab treatment showed early reduction in the PASI total score (mean ± SD) from 13.3 ± 9.02 at baseline to 2.3 ± 3.99 at 3 months; a similar trend was observed for PASI sub-scores for erythema (4.8 ± 3.21 to 0.9 ± 1.44), thickening (4.3 ± 3.00 to 0.7 ± 1.33) and scaling (4.2 ± 3.04 to 0.7 ± 1.30). The reduction in PASI total and sub-scores were sustained up to 36 months. Psoriasis Symptom Diary component scores related to redness, cracking, and scaling showed a similar reduction from baseline at 3 months that was also sustained up to 36 months. PASI regional scores for each body region showed reduction at 3 months with disease in the lower limbs being more treatment resistant. Safety profile of secukinumab was consistent with its established safety profile without any new or unexpected signals. CONCLUSIONS: Overall, an early and sustained resolution of erythema, thickening, and scaling was observed. Improvements were evident across all body regions, with the most persistent disease seen in the lower limbs. Trends in disease severity, as assessed by physicians using PASI, broadly reflected the trend in the comparable questions of the Psoriasis Symptom Diary assessed by patients.

Economic burden of moderate to severe plaque psoriasis in Canada.

BACKGROUND: Psoriasis is a chronic debilitating disease affecting approximately one million Canadians. The objective of this study is to estimate the economic burden in $CDN (2008) of moderate to severe plaque psoriasis among Canadian adults. METHODS: Using a cross-sectional design, direct resource use, costs, lost productivity, and quality of life were obtained for 90 subjects diagnosed with psoriasis in three dermatology clinics in British Columbia, Ontario, and Québec. An Excel-based economic model was developed to project the annual cost of psoriasis, from the societal perspective. RESULTS: The estimated mean annual cost of psoriasis was $7999/subject (95% CI: $3563-$12,434) with direct costs accounting for 57%. Mean lost productivity costs, which accounted for 43% of the mean annual costs of psoriasis, were $3442/subject (95% CI: $1293-$5590). CONCLUSION: Projecting the mean costs per patient to the afflicted population yields an estimated total annual cost of $1.7 billion (95% CI: $0.8-$2.6 billion) attributable to moderate to severe psoriasis in Canada. Understanding the interplay between direct costs, lost productivity, and quality of life is critical for accurately identifying and evaluating effective treatments for this disease.

Topical psoriasis therapy in the age of biologics: evidence-based treatment recommendations.

BACKGROUND: Although the range of therapeutic options has expanded dramatically in recent years, topical agents remain ubiquitous and indispensable tools for treating psoriasis at all levels of severity. The 2009 Canadian psoriasis guidelines considered evidence supporting various monotherapies and combination regimens. OBJECTIVE: Here we review all approved topical agents, including corticosteroids, calcineurin inhibitors, vitamin D analogues, and retinoids, used in psoriasis and develop additional treatment recommendations, using the Scottish Intercollegiate Guidelines Network (SIGN) system to evaluate strength of evidence, as in the original guidelines. CONCLUSION: We propose that topical treatments have a place in the long-term management of patients with moderate to severe plaque psoriasis, including those receiving concomitant photo- or systemic therapy. Topical agents are effective and appropriate treatments for psoriasis as long as the physician is attentive to signs of local adverse events and seeks opportunities to reduce the dose or treatment frequency during chronic use.