Comparative effectiveness of biologics for patients with moderate-to-severe psoriasis and special area involvement: week 12 results from the observational Psoriasis Study of Health Outcomes (PSoHO).

Introduction: Psoriasis localized at the scalp, face, nails, genitalia, palms, and soles can exacerbate the disease burden. Real-world studies comparing the effectiveness of treatments for these special areas are limited. Methods: Psoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non-interventional, study comparing the effectiveness of anti-interleukin (IL)-17A biologics (ixekizumab and secukinumab) compared to other approved biologics and the pairwise comparative effectiveness of ixekizumab relative to five other individual biologics for patients with moderate-to-severe psoriasis. To determine special area involvement, physicians answered binary questions at baseline and week 12. The proportion of patients who achieved special area clearance at week 12 was assessed. Missing outcome data were imputed as non-response. Comparative treatment analyses were conducted using frequentist model averaging. Results: Of the 1,978 patients included, 83.4% had at least one special area involved at baseline with the scalp (66.7%) as the most frequently affected part, followed by nails (37.9%), face/neck (36.9%), genitalia (25.6%), and palms and/or soles (22.2%). Patients with scalp, nail, or genital, but not palmoplantar or face/neck psoriasis, had significantly higher odds of achieving clearance at week 12 in the anti-IL-17A cohort compared to the other biologics cohort. Patients with scalp psoriasis had a 10-20% higher response rate and significantly greater odds (1.8-2.3) of achieving clearance at week 12 with ixekizumab compared to included biologics. Conclusion: Biologics demonstrate a high level of clearance of special areas at week 12 in a real-world setting. Patients with scalp, nail, or genital involvement have significantly higher odds of clearance at week 12 with anti-IL-17A biologics compared to other biologics.

Use of Systemic Therapies for Treatment of Psoriasis in Patients with a History of Treated Solid Tumours: Inference-Based Guidance from a Multidisciplinary Expert Panel.

BACKGROUND: Patients with treated solid tumours (TSTs) are a highly heterogeneous population at an increased risk for malignancy compared with the general population. When treating psoriasis in patients with a history of TSTs, clinicians are concerned about the immunosuppressive nature of psoriasis therapies, the possibility of augmenting cancer recurrence/progression, and infectious complications. No direct, high-level evidence exists to address these concerns. OBJECTIVES: We aim to provide a structured framework supporting healthcare professional and patient discussions on the risks and benefits of systemic psoriasis therapy in patients with previously TSTs. Our goal was to address the clinically important question, "In patients with TSTs, does therapy with systemic agents used for psoriasis increase the risk of malignancy or malignancy recurrence?" METHODS: We implemented an inference-based approach relying on indirect evidence when direct clinical trial and real-world data were absent. We reviewed indirect evidence supporting inferences on the status of immune function in patients with TSTs. Recommendations on systemic psoriasis therapies in patients with TSTs were derived using an inferential heuristic. RESULTS: We identified five indirect indicators of iatrogenic immunosuppression informed by largely independent bodies of evidence: (1) overall survival, (2) rate of malignancies with psoriasis and systemic psoriasis therapies, (3) rate of infections with psoriasis and systemic psoriasis therapies, (4) common disease biochemical pathways for solid tumours and systemic psoriasis therapies, and (5) solid organ transplant outcomes. On the basis of review of the totality of this data, we provided inference-based conclusions and ascribed level of support for each statement. CONCLUSIONS: Prior to considering new therapies for psoriasis, an understanding of cancer prognosis should be addressed. Patients with TSTs and a good cancer prognosis will have similar outcomes to non-TST patients when treated with systemic psoriasis therapies. For patients with TSTs and a poor cancer prognosis, the quality-of-life benefits of treating psoriasis may outweigh the theoretical risks.

Patients with previously treated cancer have a higher chance of cancer recurrence compared with the general population. With cancer incidence rising worldwide, doctors across medical specialities will need to treat other medical conditions, including inflammatory diseases such as psoriasis, in these patients. Effective systemic therapies for psoriasis reduce immune cell activity. Accordingly, there are concerns that treatments for psoriasis could worsen cancer recurrence/progression and infectious complications. There is not enough quality evidence to make broad recommendations for treating other inflammatory conditions in patients with a history of cancer. To guide patient and doctor discussions, we asked: what are effective and safe treatments when patients with treated solid tumours need systemic therapy (pills or injections) for their psoriasis? We focused on patients with solid tumours and excluded blood and skin cancers. Our panel of experts, including 12 dermatologists and 3 medical oncologists, reviewed direct and indirect evidence to answer this question. Considering the totality of evidence reviewed, the expert panel drafted and rated their level of support for opinion statements on important considerations in treating patients with psoriasis who have a history of solid tumours. By making inferences on systemic psoriasis therapies in this heterogeneous population, we take the onus off individual physicians to review the indirect data. This process may help answer questions in other disease populations where direct evidence is scarce or absent. To support treatment decisions, doctors should have a guided conversation with the patient and their family on a case-by-case basis about the risks and benefits of treatment.

Clinical Implications of Targeting the JAK-STAT Pathway in Psoriatic Disease: Emphasis on the TYK2 Pathway.

Cytokines in the interleukin (IL)-23/IL-17 axis are central to psoriasis pathogenesis. Janus kinase (JAK) signal transducer and activator of transcription (STAT) regulates intracellular signalling of several cytokines (including IL-12, 23, 22, 6, 17, and interferon (IFN)-γ) in the IL-23/IL-17 axis, and, as a result, has become a therapeutic target for psoriasis treatment. Although several JAK1-3 inhibitors, with varying degrees of selectivity, have been developed for immune-mediated inflammatory diseases, use in psoriasis is limited by a low therapeutic index as anticipated by signals from other disease indications. More selective inhibition of the JAK family is an area of interest. Specifically, selective tyrosine kinase (TYK)2 inhibition suppresses IL-23/IL-17 axis signalling, and at therapeutic doses, has a favorable safety profile compared to therapeutic doses of JAK1-3 inhibitors. Phase III efficacy and safety data for the selective allosteric TYK2-inhibitor, deucravacitinib, in adult patients with moderate-to-severe plaque psoriasis is promising. Furthermore, phase II clinical trials for ropsacitinib (PF-06826647), a selective TYK2 inhibitor, and brepocitinib (PF-06700841), a JAK1/TYK2 inhibitor, have also demonstrated efficacy and an acceptable safety profile in adult patients with moderate-to-severe plaque psoriasis. Other novel TYK2 allosteric inhibitors, NDI-034858 and ESK-001, are currently being investigated in adult patients with plaque psoriasis. This article reviews the details of the JAK-STAT pathway in psoriasis pathophysiology, the rationale for selective targeting of JAKs in the treatment of psoriasis, and provides clinical perspective on clinical trial data for JAK and TYK2 inhibitors.

Review and Practical Guidance on Managing Fungal Infections in Patients With Psoriasis Receiving Anti-IL-17 Therapies.

The IL-17 signalling pathway is a major target in treatment of plaque psoriasis. IL-17 signalling contributes to chronic inflammation and epidermal hyperplasia seen in psoriatic lesions. Blocking the IL-17 signalling cascade is an effective method in treating this disease. However, IL-17 also plays a role in the immunological protection against fungal infections and therefore, patients on IL-17 biologics experience an increased rate of fungal infections, specifically Candida albicans. It is prudent that patients and physicians are aware of this risk and understand how to recognize and manage Candida infections. In this review, we examine the Candida infection rates associated with IL-17 biologics, both in clinical trials and real-world practice. We discuss common presentations associated with various types of candidiasis and propose a recommended management approach to treating these infections.

Use of Systemic Therapies for Treatment of Psoriasis in People Living with Controlled HIV: Inference-Based Guidance from a Multidisciplinary Expert Panel.

BACKGROUND: People living with human immunodeficiency virus (PLHIV) have a similar prevalence of psoriasis as the general population, though incidence and severity correlate with HIV viral load. Adequately treating HIV early renders the infection a chronic medical condition and allows PLHIV with a suppressed viral load (PLHIV-s) to live normal lives. Despite this, safety concerns and a lack of high-level data have hindered the use of systemic psoriasis therapies in PLHIV-s. OBJECTIVES: We aim to provide a structured framework that supports healthcare professionals and patients discussing the risks and benefits of systemic psoriasis therapy in PLHIV-s. Our goal was to address the primary question, are responses to systemic therapies for the treatment of psoriasis in PLHIV-s similar to those in the non-HIV population? METHODS: We implemented an inference-based approach relying on indirect evidence when direct clinical trial data were absent. In this instance, we reviewed indirect evidence supporting inferences on the status of immune function in PLHIV. Recommendations on systemic treatment for psoriasis in PLHIV were derived using an inferential heuristic. RESULTS: We identified seven indirect indicators of immune function informed by largely independent bodies of evidence: (1) functional assays, (2) vaccine response, (3) life expectancy, (4) psoriasis manifestations, (5) rate of infections, (6) rate of malignancies, and (7) organ transplant outcomes. CONCLUSIONS: Drug-related benefits and risks when treating a patient with systemic psoriasis therapies are similar for non-HIV patients and PLHIV with a suppressed viral load and normalized CD4 counts. Prior to initiating psoriasis treatment in PLHIV, HIV replication should be addressed by an HIV specialist. Exercise additional caution for patients with a suppressed viral load and discordant CD4 responses on antiretroviral therapy.

People living with human immunodeficiency virus (PLHIV) develop psoriasis as often as everyone else. We asked: what are effective and safe treatments when PLHIV need systemic therapy (pills or injections) for their psoriasis?HIV infection attacks the immune system. When HIV is not treated, the immune system declines. A less effective immune system makes it harder for the body to fight infections and certain cancers. Psoriasis is a skin condition caused by overactive immune cells. Effective psoriasis treatments reduce immune-cell activity. There are some concerns that treatments for psoriasis may not work and could worsen infections or cancers.To answer the question, we gathered 11 dermatologists and 4 HIV specialists. We reviewed the international scientific literature on PLHIV and psoriasis. The absence of direct evidence and volume of information to review made the process challenging. The end results were worthwhile.We concluded that people who are diagnosed early and take antiretroviral therapy to control their HIV infection (PLHIV-c) can live long, healthy lives. Accordingly, we determined that PLHIV-c can likely expect the same safety and efficacy for systemic psoriasis treatments as the general population. Treatment decisions should be made on a case-by-case basis through consultation with the patient and treating physician(s).Pillars of modern medicine are evidence-based care and collaborative decision-making. Too often, neither care provider nor patient are adequately informed. We have tried to fill one information gap for PLHIV and psoriasis. This process may help answer questions in other disease populations where direct evidence is scarce or absent.

Enhanced Effectiveness of Adalimumab Compared to Topical/Traditional Systemic Agents in the Treatment of Moderate to Severe Plaque Psoriasis: Results from a Canadian Observational Epidemiologic Study (COMPLETE-PS).

INTRODUCTION: Real-world evidence is important for post-marketing evaluation. Data comparing adalimumab's effectiveness and safety with traditional therapies in clinical settings are currently lacking. The aim of this study was to compare real-world effectiveness of adalimumab versus topical/traditional systemic agents for management of moderate to severe plaque psoriasis METHODS: Patients requiring change in treatment were enrolled between 2011 and 2016 and followed per routine care for up to 24 months. Achievement of Physician Global Assessment (PGA) ≤ 1.0 at 6 months was assessed with logistic regression; time to achievement was assessed using Cox regression. Additional outcomes were assessed using repeated measures mixed models. RESULTS: Patients receiving adalimumab (n = 293) versus topical/traditional systemic agents (n = 302) were more likely to achieve PGA ≤ 1.0 at 6 months (odds ratio 2.37, 95% confidence interval [CI] 1.31-4.30) in a shorter time (hazard ratio 2.14, 95% CI 1.53-3.00), reporting both lower body surface area and improved quality of life and work productivity. CONCLUSION: In this real-world study, adalimumab was more effective than topical/traditional systemic agents at reducing disease activity and improving quality of life outcomes among Canadians with moderate to severe plaque psoriasis. (NCT00799877).

Certolizumab Pegol Use in the Treatment of Moderate-to-Severe Psoriasis: Real-World Data From Two Canadian Centers.

BACKGROUND: Certolizumab pegol (CZP) is a TNF-ɑ inhibitor used to treat moderate-to-severe plaque psoriasis (PsO) in adult patients, including women of childbearing potential (WOCBP) and patients with psoriatic arthritis (PsA). There are currently limited real-world data on CZP for treatment of PsO. OBJECTIVES: To examine the use of CZP for treatment of PsO in clinical practice at two dermatology clinics in Canada. METHODS: We conducted a retrospective chart analysis of 59 patients with moderate-to-severe psoriasis receiving CZP. Clinical efficacy was measured using the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Physician Global Assessment (PGA). Drug survival was analyzed using Kaplan-Meier plots. RESULTS: Of the 59 patients, 36 (61%) were female, of whom 23 (63.9%) were WOCBP. Twenty-three (39.0%) patients received CZP as their first biologic treatment. The main reasons for choosing CZP were its efficacy in both PsO and PsA, and for WOCBP due to little or no cross-placental transfer. Improvement of symptoms was observed after 3 months of treatment and was maintained for the 12-month analysis period. After 12 months of treatment, the patients' mean PASI score decreased from 13.0 (±5.8) at baseline to 2.3 (±4.3), mean BSA score from 13.1% (±6.7%) to 1.7% (±2.6%), and mean PGA score from 3.0 (±0.6) to 0.8 (±0.6). Overall CZP drug survival rate was 76.3% at 12 months, with no difference between biologic-naive and biologic-experienced patients. CONCLUSIONS: CZP was effective and well tolerated in this cohort of patients with moderate-to-severe PsO in a real-world setting.

Practical and Relevant Guidelines for the Management of Psoriasis: An Inference-Based Methodology.

INTRODUCTION: Psoriasis (Pso) is a common, immune-mediated, chronic-relapsing, inflammatory skin disease. While a great deal is known about Pso and its treatment, there remain several treatment scenarios unaddressed by clinical studies. To be effective, treatment for Pso must alter the activity of one or more immunological pathways important in the pathogenesis of the disease. While the benefit of blocking these pathways may be apparent, there remain uncertainties regarding safety, such as infections, malignancies, and the potential for off-target effects. Existing guidelines and treatment recommendations rely primarily on clinical trial or observational data, none of which adequately address specific clinical challenges. This document describes a methodological framework for generating practical and clinically relevant guidance for situations where direct evidence is rare or absent. Guidelines implementing this framework are currently ongoing. METHODS: We develop a knowledge synthesis approach to guideline development, utilizing clinical trial data where available, and a formalized inferential decision-making process that considers indirect data coupled with structured expert opinion and analysis. This approach is best suited for situations where direct, high-level evidence is lacking. Support for each resultant recommendation is expressed as a quantified assessment of confidence. RESULTS: The topics to be addressed by this set of guidelines are ranked by clinicians and patients as areas of concern, with an emphasis on topics where high-level evidence may have limited availability. CONCLUSION: Through this novel approach, we will derive practical, informative recommendations using the best evidence available in combination with structured expert opinion to guide best practices in complex, real-world settings. Supplementary file2 (MP4 98653 kb).

Clinical guidelines aim to assist doctors in managing their patients' medical conditions. A limitation of current guidelines is that they are frequently based on randomized clinical research trials­often considered the gold standard in medical research. Clinical trials are designed to estimate the safety and effectiveness of treatment. Outside of clinical trials, doctors encounter a range of patient cases excluded from clinical trials. Our group aims to create guidelines for those clinical scenarios not adequately addressed by clinical trials. Examples include patients excluded from clinical trials, the elderly, patients with human immunodeficiency virus (HIV), and pregnant or breastfeeding women. When clinical trial data is limited, doctors must make decisions nonetheless. In certain clinical situations they are left to their own resources to consult with experts, review the data, and make inferences based on the limited data available. Instead of concluding that there is no data, the topic of interest can be broken down into components that are answerable by different types of research studies. This inference-based approach uses expert opinion and indirect evidence to support an inference-based position on topics where direct clinical data is sparse or insufficient to answer the question. This approach can be used as a complement to clinical trial data informing disease management guidelines.

A Psoriatic Patient-Based Survey on the Understanding of the Use of Vaccines While on Biologics During the COVID-19 Pandemic [Formula: see text].

BACKGROUND: Psoriatic patients who are actively receiving biologic treatment have protocols in place to achieve optimal immunity. Inactivated vaccines are safe to use during biological treatment, without interruption. Conversely, live vaccines are used with caution and likely interruption of treatment. Given the novel coronavirus (SARS-CoV-2), nation-wide administration of vaccinations is underway. OBJECTIVE: This survey gathered information on the level of education psoriatic patients have concerning vaccinations. METHODS: An electronic survey was sent to 661 patients suffering from psoriasis. Patients originated from a single solo-practitioner community-based dermatology practice. RESULTS: The average percentage of patients who understand the difference between live and inactivated vaccines between the control and study group was 36.6%. The average response to not knowing the difference between the vaccines was 36.6% and 26.6% were "unsure." When asked if it was possible to receive inactivated vaccines while on a biologic, the mass response amidst the control and study group was "unsure" (66.9%). CONCLUSION: This questionnaire demonstrates that there is a need for supplementary education about vaccines for psoriatic patients on a biologic. Physicians will need to counsel their patients on the use of potential vaccines for SARS-Cov2 while on biologics.

Cohort Using a Ceramides Containing Cleanser and Cream With Salicylic Acid for Dry, Flaking, and Scaling Skin Conditions

Introduction: The skin of subjects with dry, flaking, and/or scaling conditions is characterized by decreased water and skin lipids content among other findings. It is well understood that daily use of gentle cleansers and moisturizers may help to restore and maintain an optimal skin barrier function. A cohort study of patients with dry skin was developed to evaluate efficacy of daily use of a ceramide containing cleanser and cream that also has salicylic acid. Methods: Thirty-five adults with mild-to-moderate dry skin conditions were recruited from four dermatology centers in Canada. With consent, the subjects received twice daily treatment with the ceramides containing cleanser and cream that also has salicylic acid. Physician and subject assessed skin condition comparing baseline versus (day 0) versus day 28 (end) was scored using the Dry skin classification scale and the Global Aesthetic Improvement Scale (GAIS). Subjects also rated satisfaction, product features, quality of life aspects, safety, and tolerability. Results: Thirty-four subjects completed the treatment and study period; one was lost to follow up. Daily use of the evaluated cleanser and moisturizer significantly improved skin condition when comparing day 0 versus day 28 (+/- 5 days (end)) results. Both the physicians and subjects using the dry skin classification scale and GAIS scored a significant improvement of the dry skin condition. After treatment subjects reported a significant improvement in the quality of their professional life, self-image, and social life. The products were shown to be safe, comfortable, and well tolerated. Conclusion: The results indicated the cleanser and moisturizer to offer an effective, easy and comfortable option for dry skin conditions. J Drugs Dermatol. 2019;18(1):80-85.

Treating Psoriasis and Psoriatic Arthritis: Position Paper on Applying the Treat-to-target Concept to Canadian Daily Practice.

OBJECTIVE: To develop preliminary treat-to-target (T2T) recommendations for psoriasis and psoriatic arthritis (PsA) for Canadian daily practice. METHODS: A task force composed of expert Canadian dermatologists and rheumatologists performed a needs assessment among Canadian clinicians treating these diseases as well as an extensive literature search on the outcome measures used in clinical trials and practice. RESULTS: Based on results from the needs assessment and literature search, the task force established 5 overarching principles and developed 8 preliminary T2T recommendations. CONCLUSION: The proposed recommendations should improve management of psoriasis and PsA in Canadian daily practice. However, these recommendations must be further validated in a real-world observational study to ensure that their use leads to better longterm outcomes.

Transitioning Between Brodalumab and Secukinumab in Moderate to Severe Psoriasis: An Early Look.

BACKGROUND: Biologics have changed the way we treat moderate to severe psoriasis. Clinical trials for these patients offer the chance for those suffering from psoriasis to volunteer their time for the advancement of science while possibly gaining benefit from the efficacy of these medications.
OBJECTIVE: All clinical trials have an ending by study design. In the past, trials ended abruptly but it is more common now for transitioning to the approved or another biologic to be offered. Sometimes, study subjects leave clinical trials suddenly for reasons of lack of efficacy, safety, withdrawing consent, being lost to follow-up, or personal reasons. Presenting early experience in transitioning is important for clinicians.
METHODS: A retrospective case series of 11 patients who were exposed to brodalumab from clinical trials that ended abruptly and transitioned to secukinumab is presented.
RESULTS: This is an early descriptive experience of transitioning between two IL-17 antagonists.
LIMITATIONS: A small number of patients were available and a short follow up limited the data presented.
CONCLUSION: Transitioning between two IL-17 antagonists is an option for those patients requiring such a change.

J Drugs Dermatol. 2016;15(8):941-943.

Public Engagement with Dermatology Contents on Facebook.

BACKGROUND: The gtring presence of dermatology platforms on Facebook has been acknowledged; however, little is known about the extent to which different types of content influence the level of engagement with online users. OBJECTIVE: To assess the level of public engagement with different types of content posted on Facebook pages devoted to dermatology. METHODS: A search on Facebook identified existing pages for dermatology academic journals, professional societies, and patient-centered groups. Then the engagement rate was calculated for each content type published on the selected pages. RESULTS: The median engagement rates were 63.8% for educational posts, 41.3% for interactive posts, 27.4% for news articles, 11.8% for academic articles, and 9.3% for others. CONCLUSION: Educational posts engaged with online users the most effectively. The level of engagement is a key determinant of knowledge dissemination via online tools, and the type of content may influence the level of engagement.

Think beyond the Skin: 2014 Canadian Expert Opinion Paper on Treating to Target in Plaque Psoriasis.

OBJECTIVE: Explore the feasibility of Treat to Target in the area of psoriasis as seen in other therapeutic areas such as hypertension, hyperlipidemia, diabetes and rheumatoid arthritis. METHODS: Review validated, measurable targets for psoriasis, including physician global assessment (PGA), psoriasis area and severity index (PASI) and dermatology life quality index (DLQI). Examine principles brought forth in the published European consensus on psoriasis and develop a Canadian consensus on Treat to Target in psoriasis. RESULTS: As PASI and DLQI are not routinely used in the community setting, we are recommending target at a PGA of zero (clear). CONCLUSION: Recommend that the target is a PGA of zero (clear) as it provides a simple and measurable result that the patient and physician can clearly understand.

Newer approaches in topical combination therapy for acne.

Acne vulgaris is a common chronic inflammatory cutaneous disease involving the pilosebaceous unit. Its pathophysiology is multifactorial and complex, including obstruction of the pilosebaceous unit due to increased sebum production, abnormal keratinization, proliferation of Propionibacterium acnes (P. acnes), and inflammation. Topical agents are the most commonly used therapy for acne. First generation topicals mainly consist of single agent retinoids, benzoyl peroxide (BPO) and antibacterials that target comedones, P. acnes, and inflammation. Novel topical therapies include combination products with advanced vehicle formulations that target multiple acne pathophysiologies and offer simplified treatment regimes. For example, the combination of clindamycin and tretinoin in a unique vehicle formulation allows for progressive follicle penetration and decreased irritation, resulting in increased efficacy. Furthermore, adapalene or clindamycin with BPO combinations target comedones, inflammation, and P. acnes synergistically. These newer combination products have the potential to increase both efficacy and patient adherence when compared with single agent treatment.

Psoriasis of the nail: anatomy, pathology, clinical presentation, and a review of the literature on therapy.

Psoriasis is a chronic skin disease that affects millions of people throughout the world. Even though cutaneous signs and symptoms are the most common clinical manifestations, the nails can be involved in up to 50% of cases, and their involvement remains an important yet often overlooked aspect of the disease. There is a broad spectrum of nail dystrophies associated with psoriasis, ranging from the common pitting and loosening of the nail plate to the less frequent discoloration and splinter hemorrhages seen in the nail bed. This article discusses the normal anatomy and embryology of the nail unit as well as the current understanding of the pathogenesis of the disease. It also provides an extensive review of the existing literature with respect to psoriatic nail therapy. Although there have been many recent advances in the treatment of the cutaneous form of the disease-most notably in the field of immunotherapies-the options for nail psoriasis are far more limited. While a number of treatment alternatives currently exist for nail disease, the general paucity of clear evidence regarding these choices often makes it difficult to select the most efficient, safe, and optimal treatment for the patient. Even though the current literature has shown some support for the use of topical, intralesional, radiation, systemic, and combination therapies for nail psoriasis, the available studies lack sufficient power to extrapolate a standardized therapeutic regimen. Therefore, until better-documented evidence validating the treatment options emerges within the literature, clinicians and patients are left with a vague and relatively unproven approach to psoriatic nail disease.