Efficacy and safety of apremilast in patients with moderate-to-severe genital psoriasis: Results from DISCREET, a phase 3 randomized, double-blind, placebo-controlled trial.

BACKGROUND: Genital psoriasis can be stigmatizing, is highly prevalent among patients with psoriasis, and has limited treatment options. Apremilast is a unique oral immunomodulating phosphodiesterase 4 inhibitor approved for psoriasis treatment. OBJECTIVE: To assess the efficacy and safety of apremilast 30 mg twice daily in patients with genital psoriasis. METHODS: DISCREET, a phase 3, placebo-controlled trial (NCT03777436), randomized patients with moderate-to-severe genital psoriasis (stratified by affected body surface area <10% or ≥10%) to apremilast or placebo for a 16-week period, followed by an apremilast extension period. Week 16 results are presented. RESULTS: Patients were randomized to apremilast (n = 143) or placebo (n = 146). At Week 16, 39.6% and 19.5% of apremilast and placebo patients, respectively, achieved a modified static Physician Global Assessment of Genitalia response (primary endpoint; score of 0/1, ≥2-point reduction); treatment difference was significant (20.1%, P = .0003). Improvements in genital signs and symptoms, skin involvement, and quality of life were observed. Common treatment-emergent adverse events were diarrhea, headache, nausea, and nasopharyngitis. LIMITATIONS: Lack of active-comparator. CONCLUSIONS: Apremilast demonstrated statistically and clinically meaningful genital Physician Global Assessment responses and improvement of signs, symptoms, severity, and quality of life in this first randomized, controlled study of an oral systemic treatment in patients with genital psoriasis.

The burden of alopecia areata: A scoping review focusing on quality of life, mental health and work productivity.

Alopecia areata (AA) is a common inflammatory autoimmune disease of the hair which can have a significant negative impact on quality of life (QoL), mental health and productivity. The aim of this scoping review is to elucidate the burden of AA focusing on these three realms. Inclusion criteria included all original manuscripts with no restriction on study type or statistical method written in English (or having an English abstract). For QoL 40 articles were included, 85 for psychiatric comorbidities, and 9 for work/school absenteeism/presenteeism mostly consisting of cross-sectional and observational cohort studies. QoL impairment was detected in over 75% of patients and up to one-third reported extremely severe QoL impairments. Specific QoL dimensions with the greatest impact were embarrassment, social functioning, as well as shopping and/or housework. Cross-sectional studies assessing the psychological burden of adult patients with AA found that the presence of signs of anxiety and/or depression ranged from 30% to 68% and affected all age groups. Rates of work absenteeism and unemployment were significantly higher in AA patients compared to healthy controls. Up to 62% reported making major life decisions including relationships, education and career based on their AA. Additionally, the extensive camouflage techniques and time lost from work led to a strong financial burden for patients and the numerous physician visits added to the healthcare costs. The overall impact of AA stretches much further than simply being an aesthetic concern and can negatively impact every part of an individual's life. An individualized approach and effective treatments will help reduce the psychosocial consequences and distress and return patients to their normal state of health.

Baseline Characteristics of Canadian Patients in the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: The Psoriasis Longitudinal Assessment and Registry (PSOLAR) is a global, prospective, longitudinal, disease-based registry. It serves as a post-marketing safety commitment with a focus on patients with moderate to severe plaque psoriasis who are candidates for systemic therapy. OBJECTIVES: To describe the baseline disease demographics and clinical characteristics of a Canadian subgroup of participants enrolled in PSOLAR. METHODS: Baseline demographic/disease characteristics, medical histories, and previous psoriasis treatments for Canadian patients in PSOLAR were summarized using descriptive statistics. RESULTS: There were 1896 patients analyzed in the Canadian subgroup at 37 clinical sites, accounting for 15.7% of the global PSOLAR population. Baseline disease and clinical characteristics were as expected for a moderate to severe psoriasis population and were generally similar to the global PSOLAR population. Two distinctions were noted in the Canadian subgroup versus those enrolled globally: a higher proportion of patients were overweight/obese (84.7% vs. 80.4%) and male (61.4% vs. 54.7%). In addition, the Canadian subgroup had numerically higher historical peak disease activity (PGA score 3.35 vs. 3.1) and longer disease duration (22.3 years vs. 17.5 years). Canadian PSOLAR patients reported a variety of comorbidities, including psoriatic arthritis (31.5%), hypertension (34.6%), hyperlipidemia (24.3%), mental illness (24.1%), and inflammatory bowel disease (1.6%). CONCLUSION: The Canadian subgroup of PSOLAR patients was generally similar to those enrolled globally with respect to baseline disease demographics and clinical characteristics. Multiple comorbidities are noted in the Canadian subgroup, underscoring the need for a holistic approach to the treatment of psoriatic patients.

Prevention of Shingles in Dermatology Patients on Systemic Medications.

The lifetime risk for herpes zoster (HZ) of approximately 1 in 3 is increased with advancing age, a family history of HZ, diseases with altered immune function, immunosuppression, physical trauma and psychological stress. In dermatology, monotherapy with current biologics does not increase risk, however systemic steroids, Janus kinase inhibitors and combination biologic/conventional disease-modifying antirheumatics do. The recombinant zoster vaccine (RZV, Shingrix®), an adjuvanted non-live subunit vaccine against the glycoprotein E subunit of varicella zoster virus, is approved for prevention of HZ in adults ≥50 years of age, and adults ≥18 years of age who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression due to disease or treatment. It is administered as two 0.5 ml intramuscular injections 2-6 months apart. In immunocompromised individuals, the spacing between injections may be reduced to 1-2 months. Where possible, the first dose should be administered at least 14 days before onset of immunosuppressive treatment. Studies in immunocompetent individuals have shown high efficacy including prevention of HZ, postherpetic neuralgia and other complications, with persistence of effect 10 years after vaccination. The acceptable safety profile and efficacy in five different immunocompromised populations support its use in at-risk adult dermatologic patients.

Emerging paradigm shift toward proactive topical treatment of psoriasis: A narrative review.

Psoriasis (PsO) requires safe and effective long-term management to reduce the risk of recurrence and decrease the frequency of relapse. Topical PsO therapies are a cornerstone in the management of PsO though safety concerns limit the chronic, continuous use of topical corticosteroids and/or vitamin D3 analogs. Evidence-based guidelines on optimal treatment targets and maintenance therapy regimens are currently lacking. This review explores the evidence supporting approaches to maintenance topical therapy for PsO including continuous long-term therapy, chronic intermittent use, step-down therapy, sequential or pulse therapy regimens, and proactive maintenance therapy. Several unaddressed questions are discussed including how and when to transition from acute to maintenance therapy, strategies for monitoring long-term treatment, the role of topical maintenance therapy in the context of systemic and biologic therapies, risks of maintenance therapy, prescribing a topical preparation suitable for patients' preferences and skin type, and key concepts for patient education to maximize long-term outcomes. Overall, emerging evidence supports a paradigm shift toward proactive treatment once skin is completely clear as a strategy to enhance disease control without compromising safety.

Fixed Combination Halobetasol Propionate and Tazarotene Lotion for Plaque Psoriasis.

A novel fixed combination lotion containing the super-potent corticosteroid halobetasol propionate 0.01% and retinoid tazarotene 0.045% (Duobrii™) has recently been introduced and indicated for the treatment of moderate to severe plaque psoriasis in adults. Studies have shown that there is synergy between the ingredients and that the product can be safely used intermittently for up to 1 year. Treatment success (i.e., Investigator Global Assessment [IGA] of clear/almost clear [IGA 0/1] and at least a 2-grade improvement from baseline) occurred in 58.8% of participants at some point in a 1-year clinical trial. Persistence of treatment success is common after treatment discontinuation. Most treatment-emergent adverse events are application site reactions, mild to moderate in intensity, and occur primarily during the first 12 weeks. Counselling should be considered to optimize treatment outcomes.

Ixekizumab Results in Persistent Clinical Improvement in Moderate-to-Severe Genital Psoriasis During a 52 Week, Randomized, Placebo-Controlled, Phase 3 Clinical Trial.

Ixekizumab was efficacious in treating moderate-to-severe genital psoriasis over 12 weeks. We evaluated the long-term efficacy and safety of ixekizumab for up to 52 weeks. Patients were randomized to 80 mg ixekizumab every 2 weeks or to placebo through Week 12, then received 80 mg open-label ixekizumab every 4 weeks through Week 52. In patients initially randomized to ixekizumab, clear or almost clear genital skin was achieved for 73% of patients at Week 12 and 75% at Week 52. Persistent improvements were also observed for overall psoriasis, genital itch, and the impact of genital psoriasis on the frequency of sexual activity. The safety profile was consistent with studies of ixekizumab in patients with moderate-to-severe plaque psoriasis. Ixekizumab provided rapid and persistent improvements in the signs and symptoms of genital psoriasis for up to 52 weeks of treatment.

Multidisciplinary Real-World Experience With Bilastine, a Second Generation Antihistamine

Introduction: Allergic conditions frequently require treatment with antihistamines. First-generation antihistamines can potentially interfere with restful sleep, cause "morning after" effects, impair learning and memory, and reduce work efficiency. Second-generation antihistamines, such as bilastine, have been demonstrated to decrease allergy symptoms effectively without causing night-time sleep disturbances and related adverse events. Method: A real-world case project was developed to help optimize patient care by recognizing the role bilastine can play for allergic conditions where antihistamine treatment is needed. The presented real-world patient cases conducted by the panel members are supported with evidence from the literature, where available. Any discussion concerning off-label use should be considered an expert opinion only. Results: The real-world cases presented here used bilastine in conditions such as perennial and seasonal allergic rhinitis, chronic urticaria, as well as urticarial vasculitis and pruritus associated with inflammatory skin conditions. The treated patients were between 9 and 76-years old providing information on a full spectrum of patients that require treatment with antihistamines. Conclusions: The presented real-world cases using the second-generation antihistamine, bilastine, demonstrated favorable outcomes for the treated patients. While effectively relieving symptoms, the antihistamine was reported to be safe and well-tolerated. J Drugs Dermatol. 2020;19(2)145-154. doi:10.36849/JDD.2020.4835

Off-Label Use of Topical Calcineurin Inhibitors in Dermatologic Disorders.

Off-label prescribing is a common practice in dermatology, particularly when uncommon dermatologic diseases have limited or no approved treatment options. Topical calcineurin inhibitors are approved for the treatment of eczema, and their anti-inflammatory, immunomodulatory, and steroid-sparing effects make them an attractive therapeutic option for a wide variety of other dermatologic diseases. This review summarizes and qualifies the available evidence supporting the clinical effectiveness of tacrolimus ointment and pimecrolimus cream in non-eczema indications. There is high-quality evidence supporting the effectiveness of topical calcineurin inhibitors in multiple dermatological disorders including vitiligo; psoriasis of the face, folds, and genitals; seborrheic dermatitis; chronic hand dermatitis; contact dermatitis; oral lichen planus; lichen sclerosus; morphea; and cutaneous lupus erythematosus. Lower-quality evidence suggests they may be considered as an option in many other cutaneous disorders.

Clinical Insights About Topical Treatment of Mild-to-Moderate Pediatric and Adult Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin condition, also referred to as atopic eczema, that is identified by itching and recurrent eczematous lesions. It often starts in infancy where it affects up to 20% of children but is also highly prevalent in adults. AD inflicts a significant psychosocial burden on patients and their families and increases the risk of other immune-mediated inflammatory conditions, such as asthma and allergic rhinitis, food allergy, and mental health disorders. It is a lifelong condition associated with epidermal barrier dysfunction and altered immune function. Through the use of emollients and anti-inflammatory agents, current prevention and treatment therapies attempt to restore epidermal barrier function. Acute flares are treated with topical corticosteroids. Topical calcineurin inhibitors (TCIs) and topical corticosteroids (TCSs) are used for proactive treatment to prevent remission. There remains a need and opportunity to improve AD care through future research directed toward an improved understanding of the heterogeneity of the disease and its subtypes, the role of autoimmunity in its pathogenesis, the mechanisms behind disease-associated itch and response to specific allergens, and the comparative effectiveness and safety of therapies.

Treating to Target(s) With Interleukin-17 Inhibitors.

BACKGROUND:: The treat-to-target (T2T) strategy has become established in several medical specialties as a key guidance to optimal therapeutic decision making. T2T may be effective in the assessment of the biologic class of agents called interleukin (IL)-17 inhibitors, which are emerging as a safe and effective treatment option for autoimmune inflammatory conditions such as plaque psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS). OBJECTIVE:: The objective of this article is to use a T2T approach for the evaluation of the effectiveness and safety of IL-17 inhibitors in the management of patients with plaque psoriasis, PsA, and AS. METHODS:: Following a comprehensive literature search, a full-day meeting was convened to discuss and identify the T2T targets for psoriasis, PsA, and AS. Clinical trial evidence was presented for the approved IL-17 inhibitors-secukinumab, ixekizumab, and brodalumab-to assess whether these data meet T2T safety and efficacy targets. RESULTS:: All 3 approved agents were significantly superior to placebo and active controls in the achievement of T2T targets for psoriasis. Secukinumab and ixekizumab were likewise associated with significantly better outcomes than controls in the PsA targets, and secukinumab resulted in significant AS target improvements vs placebo. The IL-17 inhibitors were also associated with low rates of serious adverse events and exacerbations of common comorbid conditions. CONCLUSION:: Phase III trial results support the T2T benefit and safety of IL-17 inhibitors according to their specific indications for the management of patients with plaque psoriasis, PsA, and AS.

Checklist for the Systemic Treatment of Psoriasis Using Biologics: A Delphi Study.

BACKGROUND: Despite the complexity of psoriasis treatment using biologic therapy, there does not exist a standardized synoptic reporting form for the initiation of this population. The purpose of this study was to use a modified Delphi approach to develop a standard checklist for the standardized documentation of patients receiving systemic biologic therapy for psoriasis. METHODS: A modified Delphi survey was conducted over 3 rounds (February 2017 through January 2018). An expert panel generated a 51-item checklist that was proposed to participants. Items were rated on an anchored 1-7 Likert scale. Consensus was defined apriori as ≥ 70% agreement by respondents. RESULTS: A total of 58, 17, and 18 dermatologists participated in 3 consecutive Delphi rounds, respectively. Only half of the dermatologists surveyed reported using a checklist for the management of psoriasis. The final checklist comprised 19, 5, 6, and 9 items pertaining to patient history; physical exam and history of systemic therapy; vaccinations; and lab investigations and bloodwork, respectively. CONCLUSIONS: Given the increasing availability and complexity of biologic agents for psoriasis treatment, there is a need to promote standardized documentation for this population. The Checklist for the Systemic Treatment of Psoriasis presents 38 items that should be considered when initiating patients with psoriasis on biologic therapy.

Canadian Patients' Preferences in Topical Psoriasis Care: Insights From the PROPEL Surveys.

BACKGROUND: Patients with psoriasis of all severities employ topical treatment, either alone or in combination. Promoting Patient Engagement at the Leading Edge of Topical Psoriasis Treatment (PROPEL) surveyed Canadian dermatologists and their patients about their attitudes toward topical care. OBJECTIVES: To identify gaps between patients and dermatologists regarding the burden of psoriasis, the burden of treatment, and priorities for topical care to Canadian patients with psoriasis. METHODS: Two parallel surveys explored patient attitudes toward psoriasis and their experience with topical care, as expressed by patients or as perceived by their dermatologists. A third survey, addressed to patients, included additional questions regarding treatment adherence to current topical treatment regimens. RESULTS: PROPEL dermatologists underestimated the burden associated with psoriatic itch. Otherwise, they were well aligned with patients' views, including their preference for maintaining topical care of their psoriasis over other treatment modalities, the nature of good psoriasis control, and desirable features of topical medications. Despite holding generally positive views of topical therapy, many patients self-identified as poorly adherent. CONCLUSIONS: Long-term adherence to psoriasis topical care remains a challenge. Formulations with improved acceptability might help patients maintain good adherence.

A Treatment Algorithm for Moderate to Severe Atopic Dermatitis in Adults.

BACKGROUND: Atopic dermatitis (AD) is a common and chronic inflammatory skin disease. Approximately 10% of adults with AD do not respond adequately to topical therapies and require phototherapy and/or systemic therapy. OBJECTIVE: To provide a patient-focused approach to the identification and management of adults with AD who require systemic treatment. METHODS: A working group of clinicians experienced in managing AD was convened to review and discuss current evidence on the identification and clinical management of adults with moderate to severe AD. RESULTS: We propose a set of simple and practical clinical criteria for selecting candidates for systemic treatment of AD based on their response to first-line topical therapy and 4 clinical measures that are easily incorporated into routine practice. We also suggest a framework for evaluating systemic treatments according to attributes that are important from both a clinician's and a patient's perspective. An algorithm was developed proposing a pathway for treatment of moderate to severe AD in adults. CONCLUSION: Adults with moderate to severe AD that does not respond adequately to topical therapies currently have few safe and effective treatment options. A clinical algorithm could help guide treatment decisions.

The Static Physician's Global Assessment of Genitalia: A Clinical Outcome Measure for the Severity of Genital Psoriasis.

Introduction: Genital psoriasis is a common but frequently overlooked manifestation of psoriasis with a considerable impact on patients' quality of life. Currently no validated clinical trial outcome measures exist to assess genital psoriasis severity that meet regulatory agency requirements. Methods: This study describes the development of the static Physician's Global Assessment of Genitalia (sPGA-G) scale, a clinical outcome measure for the assessment of genital psoriasis severity that accounts for the erythematous clinical presentation of genital psoriasis. The reliability of the sPGA-G was evaluated using scores collected from clinician assessments of photographs of genital psoriasis cases. Scores were collected from 10 academic and clinical experts in genital psoriasis and 95 clinician assessors who participated in either in-person (n=28) or online (n=67) sPGA-G training modules. Results: The sPGA-G had a high inter-rater reliability (IRR, measured by Kendall's W) for expert raters (W=0.856, P less than 0.0001), in-person assessors (W=0.822, P less than 0.0001), and online assessors (W=0.678, P less than 0.0001). IRR was also high for all clinical assessors combined, (W=0.714, P less than 0.0001). Discussion: This study demonstrates that the sPGA-G is an intuitive and reliable clinical outcome measure that specifically measures the severity of genital psoriasis. J Drugs Dermatol. 2017;16(8):793-799.

How Mohs Surgery Transformed Into a First-Line Treatment of Skin Cancer.

Mohs surgery is considered ideal treatment for many types of skin cancers. Developed by Dr Frederic Edward Mohs (1910-2002), Mohs surgery allows all surgical margins to be viewed microscopically, ensuring no cancer cells go unremoved, yet it failed to achieve immediate acceptance when first introduced in the 1940s. A catalyst to the widespread acceptance of Mohs surgery occurred with the work of dermatologic colleagues who reported excellent results without using the paste. It suggested the real innovation of Mohs surgery lay in its microscopic control and not the paste, the discontinuation of which removed all the problems associated with its use.

Acitretin Use in Dermatology.

BACKGROUND: Acitretin has been used for the treatment of severe psoriasis for over 20 years. OBJECTIVE: The current project was conceived to optimise patient care by recognising the role acitretin can play in the treatment of patients with psoriasis and those with other disorders of keratinisation. METHODS: A literature review was conducted to explore the role of acitretin and to assess its value for dermatologic disorders other than severe psoriasis. A panel of Canadian dermatologists developed a clinical pathway using a case-based approach, focusing on specific patient features. RESULTS: The clinical pathway covers plaque psoriasis with hyperkeratotic plantar disease, palmoplantar pustulosis, hyperkeratotic hand dermatitis, lichen planus, lamellar ichthyosis, and hidradenitis suppurativa. CONCLUSION: The recommendations in our clinical pathway reflect the current use of acitretin in Canada for severe psoriasis and other disorders of keratinisation.

Review of Systemic Treatment Options for Adult Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease resulting from defects in skin barrier and aberrant immune responses. AD significantly affects the quality of life. Not all patients respond to topical therapies, and often systemic therapy is required to control the disease. OBJECTIVE: To review the treatment options for adult AD patients including those options for patients who do not respond adequately or have contraindications to oral systemic therapy. METHODS: A working group of clinicians with experience managing AD was convened to review the current literature on treatment options for adult AD patients. This review is based on the best available evidence from a published systematic review and an additional literature search. RESULTS: Current treatments for AD are reviewed, including options for adult AD patients who do not respond or have contraindications to current systemic therapies. A new approach with targeted therapies is reviewed based on best available evidence. CONCLUSION: Many AD patients respond satisfactorily to topical or systemic treatments, but for those patients who do not respond or have contraindications, new biologic agents appear to be promising therapies.

Development of a Clinical Pathway for Atopic Dermatitis Patients: A Case-Based Approach.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin condition, associated with significant patient morbidity. There are a myriad of excellent evidenced based guidelines to guide clinicians by an extensive review of all the available treatments. However, while well written and complete these papers may not always allow easy transition to clinical application. OBJECTIVE: The purpose of this paper was to develop a practical case-based approach for the treatment and maintenance of AD, enabling translation of guidelines into clinical care. METHODS: After literature searches, selected AD trials and recent existing guidelines were reviewed. Using a nominal group process for consensus, an expert panel of Canadian dermatologists determined the case features and corresponding treatments. RESULTS: A patient focused clinical pathway with 7 cases was developed. For each case scenario, treatment for mild, moderate, and severe disease was recommended. CONCLUSION: A practical case-based clinical pathway was developed for easy clinical application and optimal patient care. J Drugs Dermatol. 2016;15(12):1485-1494.

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.