INDIVIDUAL ARTICLE: NECOM 3: A Practical Algorithm for the Management of Radiation Therapy-Related Acute Radiation Dermatitis.

BACKGROUND: In the Nordic European countries in 2020, cancer diagnoses accounted for 175,925 patients. About 50% of cancer patients receive radiation therapy (RT), which may lead to radiation dermatitis (RD). Notably, patients with breast, head, neck, and anal cancers may be prone to developing RD. However, few algorithms exist for the prevention and treatment of RD. METHODS: The Nordic European Cutaneous Oncodermatology Management (NECOM) project aims to improve cancer patient outcomes by offering tools to prevent and treat cancer therapy-related cutaneous adverse events (cAEs). The first 2 NECOM papers presented various cAEs and skincare regimens involving hygiene, moisturization, sun protection, and camouflage products for preventing and managing cAEs. The NECOM 3 practical algorithm for preventing and managing acute RD (ARD) is intended to promote healthy skin and reduce RT-related ARD, improving cancer patient outcomes.  Results: The NECOM advisors discussed the results of a systematic literature review and obtained consensus on the evidence and opinion-based practical algorithm for ARD to support all stakeholders in the Nordic European healthcare setting. The algorithm starts with skin-preserving therapy, followed by skin condition assessment and patient-specific interventions based on the grade of RD present.  Conclusion: ARD may lead to symptoms of pruritus and pain, decreased QoL and morbidity, and treatment interruptions. Patient education on the prevention of RD and treatment recommendations given in the NECOM 3 algorithm may help prevent and manage RD and improve the overall care of patients receiving RT. J Drugs Dermatol. 2023;22:11(Suppl 2):s3-s10.

Psoriasis and Skin Barrier Dysfunction: The Role of Gentle Cleansers and Moisturizers in Treating Psoriasis.

BACKGROUND: Psoriasis is a chronic immune-mediated dermatologic disorder with multisystemic comorbidities, which is effectively treated with a range of prescription therapies. Studies have reported epidermal barrier abnormalities in the lesional skin of psoriasis patients; however, there is currently insufficient information about skin barrier function in psoriasis patients. This review discusses the potential role of gentle cleansers and moisturizers in the management of psoriasis and in promoting a healthy skin barrier. METHODS: A literature review was followed by the authors' discussions and agreement on 5 statements to provide expert guidance for gentle cleansers and moisturizer use in psoriasis patients. RESULTS: In a workshop, the authors provided feedback on 15 draft statements created prior to the meeting, and agreed upon 5 statements. The authors agreed that guidelines rarely mention skincare for psoriasis patients, demonstrating a potential knowledge gap. Skincare may play a role in managing psoriasis as an adjuvant treatment of acute psoriasis and for maintenance treatment of healing skin during asymptomatic periods. Studies of patients with psoriasis applying topical moisturizers (such as those containing salicylic acid or ceramides) showed softened plaques, enhancing the absorption of topical treatments such as corticosteroids. Studies applying ceramide-containing skincare showed an overall improvement in the appearance of the skin and provided relief for psoriasis. CONCLUSION: The authors agreed that skincare and barrier restoration in treating psoriasis is a relatively new concept for most dermatologists. There is a need to develop a more robust body of evidence on skincare for psoriasis to influence clinical practice in a meaningful way. Kircik L, Alexis AF, Andriessen A, et al. Psoriasis and skin barrier dysfunction: the role of gentle cleansers and moisturizers in treating psoriasis. J Drugs Dermatol. 2023;22(8):773-778. doi:10.36849/JDD.7411.

Efficacy of Roflumilast Foam, 0.3%, in Patients With Seborrheic Dermatitis: A Double-blind, Vehicle-Controlled Phase 2a Randomized Clinical Trial.

Importance: Current topical treatment options for seborrheic dermatitis are limited by efficacy and/or safety. Objective: To assess safety and efficacy of roflumilast foam, 0.3%, in adult patients with seborrheic dermatitis affecting the scalp, face, and/or trunk. Design, Setting, and Participants: This multicenter (24 sites in the US and Canada) phase 2a, parallel group, double-blind, vehicle-controlled clinical trial was conducted between November 12, 2019, and August 21, 2020. Participants were adult (aged ≥18 years) patients with a clinical diagnosis of seborrheic dermatitis for a 3-month or longer duration and Investigator Global Assessment (IGA) score of 3 or greater (at least moderate), affecting 20% or less body surface area, including scalp, face, trunk, and/or intertriginous areas. Data analysis was performed from September to October 2020. Interventions: Once-daily roflumilast foam, 0.3% (n = 154), or vehicle foam (n = 72) for 8 weeks. Main Outcomes and Measures: The main outcome was IGA success, defined as achievement of IGA score of clear or almost clear plus 2-grade improvement from baseline, at week 8. Secondary outcomes included IGA success at weeks 2 and 4; achievement of erythema score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8; achievement of scaling score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8; change in Worst Itch Numeric Rating Scale (WI-NRS) score from baseline; and WI-NRS success, defined as achievement of 4-point or greater WI-NRS score improvement in patients with baseline WI-NRS score of 4 or greater. Safety and tolerability were also assessed. Results: A total of 226 patients (mean [SD] age, 44.9 [16.8] years; 116 men, 110 women) were randomized to roflumilast foam (n = 154) or vehicle foam (n = 72). At week 8, 104 (73.8%) roflumilast-treated patients achieved IGA success compared with 27 (40.9%) in the vehicle group (P < .001). Roflumilast-treated patients had statistically significantly higher rates of IGA success vs vehicle at week 2, the first time point assessed. Mean (SD) reductions (improvements) on the WI-NRS at week 8 were 59.3% (52.5%) vs 36.6% (42.2%) in the roflumilast and vehicle groups, respectively (P < .001). Roflumilast was well tolerated, with the rate of adverse events similar to that of the vehicle foam. Conclusions and Relevance: The results from this phase 2a randomized clinical trial of once-daily roflumilast foam, 0.3%, demonstrated favorable efficacy, safety, and local tolerability in the treatment of erythema, scaling, and itch caused by seborrheic dermatitis, supporting further investigation as a nonsteroidal topical treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04091646.

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.

Efficacy and Safety of Dupilumab Maintained in Adults ≥ 60 Years of Age with Moderate-to-Severe Atopic Dermatitis: Analysis of Pooled Data from Four Randomized Clinical Trials.

BACKGROUND: Adults aged ≥ 60 years are often underrepresented in atopic dermatitis (AD) clinical trials; age-related comorbidities may impact treatment efficacy and safety. OBJECTIVE: The aim was to report dupilumab efficacy and safety in patients aged ≥ 60 years with moderate-to-severe AD. METHODS: Data were pooled from four randomized, placebo-controlled dupilumab trials of patients with moderate-to-severe AD (LIBERTY AD SOLO 1 and 2, LIBERTY AD CAFÉ, and LIBERTY AD CHRONOS) and stratified by age (< 60 [N = 2261] and ≥ 60 [N = 183] years). Patients received dupilumab 300 mg every week (qw) or every 2 weeks (q2w), or placebo with/without topical corticosteroids. Post hoc efficacy at week 16 was examined using broad categorical and continuous assessments of skin lesions, symptoms, biomarkers, and quality of life. Safety was also assessed. RESULTS: In the ≥ 60-year-old group at week 16, a greater proportion of dupilumab-treated patients achieved an Investigator's Global Assessment score of 0/1 (q2w: 44.4%; qw: 39.7%) and 75% improvement in Eczema Area and Severity Index (63.0%; 61.6%) versus placebo (7.1% and 14.3%, respectively; P < 0.0001). Type 2 inflammation biomarkers (immunoglobulin E and thymus and activation-regulated chemokine) were also significantly reduced in dupilumab- versus placebo-treated patients (P < 0.01). Results were similar in the < 60-year-old group. The exposure-adjusted incidences of adverse events in dupilumab-treated patients were generally similar to those receiving placebo, with numerically fewer treatment-emergent adverse events in the dupilumab-treated ≥ 60-year-old group versus placebo. LIMITATIONS: There were fewer patients in the ≥ 60-year-old group; post hoc analyses. CONCLUSION: Dupilumab improved AD signs and symptoms in patients aged ≥ 60 years; results were comparable to those in patients aged < 60 years. Safety was consistent with the known dupilumab safety profile. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02277743, NCT02277769, NCT02755649, NCT02260986. Does dupilumab benefit adults aged 60 years and older with moderate-to-severe atopic dermatitis?(MP4 20,787 KB).

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.

Treatments for Primary Delusional Infestation: Systematic Review.

BACKGROUND: Delusional infestation, also known as Ekbom syndrome, is a rare delusional disorder characterized by the fixed belief that one is infested with parasites, worms, insects, or other organisms. Although delusional infestation is a psychiatric condition, patients often consult dermatologists with skin findings, and it is currently unclear what treatments are recommended for this disorder. OBJECTIVE: We aimed to systematically review and describe the treatment and management of patients presenting with primary delusional infestation. METHODS: A systematic search was conducted using Ovid on MEDLINE, Embase, PsycINFO, and the Cochrane Register of Clinical Trials. Relevant data, including treatment, dosage, response, adherence, and side effects, were extracted and analyzed. RESULTS: A total of 15 case series were included, comprising 280 patients (mean age 53.3 years, 65.4% female) with delusional infestation. Overall, aripiprazole had the highest complete remission rate at 79% (11/14), although this was limited to 14 patients. Among drug classes, selective serotonin reuptake inhibitors were the most effective with a 79% (11/14) complete remission rate and 43% (9/21) partial remission rate in patients with comorbid depression, anxiety, or trichotillomania. First-generation antipsychotics and second-generation antipsychotics had similar complete remission rates (56/103, 54.4% vs 56/117, 47.9%, respectively) and partial remission rates (36/103, 35% vs 41/117, 35%, respectively). CONCLUSIONS: Due to the rarity of delusional infestation, we only found 15 case series. However, we found that first-generation antipsychotics appear to be similar in effectiveness to second-generation antipsychotics for the treatment of primary delusional infestation. Larger studies and randomized controlled trials are needed to evaluate the efficacy of pharmacological therapy for delusional infestation. TRIAL REGISTRATION: PROSPERO CRD42020198161; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198161.

The Impact of Acne Treatment on Skin Bacterial Microbiota: A Systematic Review.

BACKGROUND: Microbial strains such as Cutibacterium acnes have been examined as contributors to the pathogenesis of acne. Given the prevalence of the disease among adolescents and adults, the overutilization of antimicrobial agents may breed resistance and alter commensal microflora. OBJECTIVES: To characterize the impact of acne treatment on the diversity and relative abundance of the cutaneous microbial community, particularly of the bacterial flora. METHODS: An electronic search was conducted of Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) on June 5, 2020. Interventional and observational studies examining patients receiving acne treatment with culture-independent, community-level analysis of the cutaneous microbiome were included. RESULTS: Nine studies with 170 treated acne patients were included. Five studies reported a significant change in alpha diversity following treatment, 3 of which examining systemic antibiotics reported significant increases in diversity. Two of 3 studies examining effects of benzoyl peroxide reported a decrease in diversity. However, trends in diversity were heterogeneous among studies. CONCLUSIONS: While individual variability in microbiome composition, and study-level heterogeneity in study sampling techniques may limit quantitative synthesis, our results support findings that acne treatment, including those not considered to have antimicrobial properties, alters the composition of the cutaneous microbiome.PROSPERO registration: CRD42020190629.

Risk of Vulvar Squamous Cell Carcinoma in Lichen Sclerosus and Lichen Planus: A Systematic Review.

OBJECTIVES: The objectives of this study were to determine: 1) the prevalence of lichen sclerosus (LS) and lichen planus (LP) present in association with vulvar squamous cell carcinoma (VSCC), and 2) the incidence and absolute risk of developing VSCC in LS and LP. METHODS: A search was performed of MEDLINE, EMBASE and CINAHL databases. Three independent reviewers screened articles published before September 1, 2020, first on title/abstract and then on the full text. Women with a history of VSCC, human papillomavirus, smoking, or autoimmune disease were excluded. Newcastle-Ottawa observational study scales were used to assess the risk of bias and methodological quality of the included studies. Of the 3132 studies assessed, 31 were selected for analysis. Due to study heterogeneity, a qualitative synthesis was conducted. RESULTS: The prevalence of LS and LP in association with VSCC ranged from 0% (95% CI 0-5) to 83% (95% CI 36-100) and 1% (95% CI 0-7) to 33% (95% CI 4-78), respectively. The incidence of VSCC ranged from 1.16 (95% CI 0.03-6.44) to 13.67 (95% CI 5.50-28.17) per 1000 person-years for LS. The absolute risk of developing VSCC in patients ranged from 0.0% (95% CI 0.0-5.52) to 21.88% (95% CI 9.28-39.97) with LS and was 1.16% (95% CI 0.1-4.1) with LP. Incidence was not calculable for LP owing to study characteristics. CONCLUSIONS: This review provides evidence that there is an increased risk of developing VSCC in women with LS, while associations with LP are less clear. Early identification, treatment, and long-term follow-up are essential to prevent potential malignant progression of these vulvar dermatoses.

Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial.

BACKGROUND: The heterogeneous course of moderate-to-severe atopic dermatitis necessitates treatment flexibility. OBJECTIVE: We evaluated the maintenance of abrocitinib-induced response with continuous abrocitinib treatment, dose reduction or withdrawal, and response to treatment reintroduction following flare (JAK1 Atopic Dermatitis Efficacy and Safety [JADE] REGIMEN: National Clinical Trial 03627767). METHODS: Patients with moderate-to-severe atopic dermatitis responding to open-label abrocitinib 200 mg monotherapy for 12 weeks were randomly assigned in a 1:1:1 ratio to blinded abrocitinib (200 or 100 mg) or placebo for 40 weeks. Patients experiencing flare received rescue treatment (abrocitinib 200 mg plus topical therapy). RESULTS: Of 1233 patients, 798 responders to induction (64.7%) were randomly assigned. The flare probability during maintenance was 18.9%, 42.6%, and 80.9% with abrocitinib 200 mg, abrocitinib 100 mg, and placebo, respectively. Among patients with flare in the abrocitinib 200 mg, abrocitinib 100 mg, and placebo groups, 36.6%, 58.8%, and 81.6% regained investigator global assessment 0/1 response, respectively, and 55.0%, 74.5%, and 91.8% regained eczema area and severity index response, respectively, with rescue treatment. During maintenance, 63.2% and 54.0% of patients receiving abrocitinib 200 and 100 mg, respectively, experienced adverse events. LIMITATIONS: The definition of protocol-defined flare was not established, limiting the generalizability of findings. CONCLUSION: Induction treatment with abrocitinib was effective; most responders continuing abrocitinib did not flare. Rescue treatment with abrocitinib plus topical therapy effectively recaptured response.

Therapeutic Options for the Treatment of Darier's Disease: A Comprehensive Review of the Literature.

Darier's disease (also known as keratosis follicularis or dyskeratosis follicularis) is an autosomal dominant inherited disorder which manifests as hyperkeratotic greasy papules in the first or second decade of life. Aside from symptom management and behavioral modifications to avoid triggers, there are currently no validated treatments for Darier's disease (DD). However, a variety of treatments have been proposed in the literature including retinoids, steroids, vitamin D analogs, photodynamic therapy, and surgical excision. The purpose of this review article is to identify therapeutic options for treating DD and to outline the evidence underlying these interventions. A search was conducted in Medline for English language articles from inception to July 4, 2020. Our search identified a total of 474 nonduplicate studies, which were screened by title and abstract. Of these, 155 full text articles were screened against inclusion/exclusion criteria, and 113 studies were included in our review. We identified Grade B evidence for the following treatments of DD: oral acitretin, oral isotretinoin, systemic Vitamin A, topical tretinoin, topical isotretinoin, topical adapalene gel, topical 5-flououracil, topical calciptriol and tacalcitol (with sunscreen), grenz ray radiation, and x-ray radiation. All other evidence for treatments of DD consisted of case reports or case series, which is considered grade C evidence. Considering the quality and quantity of evidence, clinicians may consider initiating a trial of select topical or oral retinoids first in patients with localized or generalized DD, respectively.

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.

Practical Management of Patients with Atopic Dermatitis on Dupilumab.

INTRODUCTION: Dupilumab is approved to treat moderate-to-severe atopic dermatitis (AD) in several countries in patients as young as 6 years of age. Since its approval, practical issues related to the use of dupilumab for AD have arisen, with particular interest in transitioning from current therapies and managing medication overlap, considerations for special populations of patients with AD, and management of potential adverse events. METHODS: This article aims to review the literature addressing several practical management issues related to dupilumab use for AD and to provide a framework for clinical decision-making in these circumstances and sub-populations. Each statement was reviewed, revised and voted on by authors to provide their level of agreement and degree of uncertainty for each statement. RESULTS: An agreement level > 80% was achieved for all of the statements. CONCLUSION: The expert panel provides statements considering the practical management of patients with AD taking dupilumab to inform clinical decision-making in specific but frequently encountered clinical situations.