Tapinarof cream 1% once daily: Significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials.

BACKGROUND: Tapinarof cream 1% once daily (QD), a topical aryl hydrocarbon receptor agonist, downregulates pro-inflammatory Th2 cytokines, upregulates skin-barrier components, and reduces oxidative stress. OBJECTIVE: To assess tapinarof efficacy and safety in adults and children down to 2 years of age with atopic dermatitis (AD). METHODS: Eight hundred and thirteen patients were randomized to tapinarof or vehicle QD in two 8-week phase 3 trials. RESULTS: The primary efficacy endpoint, Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and ≥2-grade improvement from baseline at Week 8, was met with statistical significance in both trials: 45.4% versus 13.9% and 46.4% versus 18.0% (tapinarof vs vehicle; both P < .0001). Significantly superior Eczema Area and Severity Index 75 (EASI75) responses were also observed with tapinarof versus vehicle at Week 8: 55.8% versus 22.9% and 59.1% versus 21.2% (both P < .0001). Rapid improvements in patient-reported pruritus were also significant with tapinarof versus vehicle. Common adverse events (≥5%) of folliculitis, headache, and nasopharyngitis were mostly mild or moderate, with lower discontinuations due to adverse events in the tapinarof groups than with vehicle. LIMITATIONS: Long-term efficacy was not assessed. CONCLUSION: Tapinarof demonstrated highly significant efficacy and favorable safety and tolerability in a diverse population of patients with AD down to 2 years of age.

Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults.

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients.

Psoriasis is a chronic, multisystem, inflammatory disease that affects approximately 1% of children, with onset most common during adolescence. This guideline addresses important clinical questions that arise in psoriasis management and provides evidence-based recommendations. Attention will be given to pediatric patients with psoriasis, recognizing the unique physiology, pharmacokinetics, and patient-parent-provider interactions of patients younger than 18 years old. The topics reviewed here mirror those discussed in the adult guideline sections, excluding those topics that are irrelevant to, or lack sufficient information for, pediatric patients.

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus).

Diagnosis and management of pemphigus: Recommendations of an international panel of experts.

BACKGROUND: Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management. OBJECTIVE: We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations. METHODS: A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus. RESULTS: The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion. LIMITATIONS: Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. CONCLUSIONS: We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.

Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa is a painful, chronic inflammatory skin disease with few options for effective treatment. In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor α, showed efficacy against hidradenitis suppurativa. METHODS: PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods. In period 1, patients were randomly assigned in a 1:1 ratio to 40 mg of adalimumab weekly or matching placebo for 12 weeks. In period 2, patients were reassigned to adalimumab at a weekly or every-other-week dose or to placebo for 24 weeks. The primary end point was a clinical response, defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts, at week 12. RESULTS: We enrolled 307 patients in PIONEER I and 326 in PIONEER II. Clinical response rates at week 12 were significantly higher for the groups receiving adalimumab weekly than for the placebo groups: 41.8% versus 26.0% in PIONEER I (P=0.003) and 58.9% versus 27.6% in PIONEER II (P<0.001). Patients receiving adalimumab had significantly greater improvement than the placebo groups in rank-ordered secondary outcomes (lesions, pain, and the modified Sartorius score for disease severity) at week 12 in PIONEER II only. Serious adverse events in period 1 (excluding worsening of underlying disease) occurred in 1.3% of patients receiving adalimumab and 1.3% of those receiving placebo in PIONEER I and in 1.8% and 3.7% of patients, respectively, in PIONEER II. In period 2, the rates of serious adverse events were 4.6% or less in all the groups in both studies, with no significant between-group differences. CONCLUSIONS: Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups. (Funded by AbbVie; ClinicalTrials.gov numbers, NCT01468207 and NCT01468233 for PIONEER I and PIONEER II, respectively.).

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis with phototherapy.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world's population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light-based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments.

Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations on the basis of available evidence.

Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics.

Psoriasis is a chronic, inflammatory multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations based on the available evidence. The treatment of psoriasis with biologic agents will be reviewed, emphasizing treatment recommendations and the role of the dermatologist in monitoring and educating patients regarding benefits as well as associated risks.

Effect of secukinumab on quality of life and psoriasis-related symptoms: A comparative analysis versus ustekinumab from the CLEAR 52-week study.

BACKGROUND: Secukinumab has demonstrated greater sustained skin clearance than ustekinumab through week 52, greater improvement in symptoms and health-related quality of life, and comparable safety profile. OBJECTIVE: To assess the impact of secukinumab versus that of ustekinumab on complete relief from psoriasis-related symptoms, time to response in terms of health-related quality of life, and cumulative benefit among patients with moderate-to-severe plaque psoriasis. METHODS: Psoriasis-related pain, itching, and scaling and the Dermatology Life Quality Index (DLQI) score were compared between treatments on the basis of time to complete relief of symptoms and time to DLQI response in the CLEAR trial. Cumulative benefit over 52 weeks based on Psoriasis Area and Severity Index score, symptom relief, and DLQI response were evaluated by area under the curve analysis. RESULTS: Significantly more patients treated with secukinumab achieved complete relief of pain at weeks 16 and 52 (all P < .05). Complete relief of itching and scaling occurred significantly faster with secukinumab (median, 4 weeks faster for itching and 8 weeks faster for scaling [P < .001]). Response as measured by the DLQI was 4 weeks faster with secukinumab (P < .0001). Cumulative benefits were greater with secukinumab (all P < .05). LIMITATIONS: Analyses were post hoc. CONCLUSION: This patient-reported outcome analysis confirms greater and sustained benefits of secukinumab versus those of ustekinumab treatment on patients' lives.

From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis.

BACKGROUND: An urgent need exists in the United States to establish treatment goals in psoriasis. OBJECTIVE: We aim to establish defined treatment targets toward which clinicians and patients with psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice. METHODS: The National Psoriasis Foundation conducted a consensus-building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre-Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds. RESULTS: A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less. LIMITATIONS: Although BSA is feasible in practice, it does not encompass health-related quality of life, costs, and risks of side effects. CONCLUSION: With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit-risk assessments of therapeutic options individualized to the patient.

Translating psoriasis guidelines into practice: Important gaps revealed.

BACKGROUND: There is a well-established lack of adherence to evidence-based clinical guidelines. The American Academy of Dermatology (AAD) developed educational sessions entitled Translating Evidence into Practice based on the published guidelines for psoriasis and psoriatic arthritis. OBJECTIVE: We sought to determine the effectiveness of Translating Evidence into Practice sessions in improving patient care. METHODS: Pre- and post-session surveys were administered at Translating Evidence into Practice sessions. A follow-up was administered 6 months after completion of the most recent session, which was 2.5 years after the first session. RESULTS: At both post-session and follow-up, more than 92% of participants believed the sessions had improved their knowledge. The proportion of participants that self-reported assessing disease severity, comorbidities, and quality of life increased at follow-up. Participants' self-reported counseling of patients and confidence in treating psoriasis and psoriatic arthritis also increased at post-session and follow-up. Greater than 97% of participants thought the sessions would have a positive impact on their practice whereas 50% reported making a change in practice. LIMITATIONS: Lack of a control group, the self-reported nature of the data, and potential participant bias are limitations. CONCLUSION: The AAD's Translating Evidence into Practice sessions are effective and well received for improving knowledge and practice and can be useful to determine self-reported practice gaps.

Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1).

BACKGROUND: Apremilast works intracellularly to regulate inflammatory mediators. OBJECTIVE: ESTEEM 1 evaluated efficacy/safety of apremilast at 30 mg twice a day for moderate to severe plaque psoriasis. METHODS: This phase III, multicenter, double-blind, placebo-controlled study randomized adults (2:1) to apremilast or placebo. At week 16, the placebo group switched to apremilast through week 32, followed by a randomized treatment withdrawal phase to week 52. Binary end points were analyzed using χ(2) test; continuous end points used analysis of covariance. RESULTS: In all, 844 patients were randomized (n = 282, placebo; n = 562, apremilast). At week 16, significantly more patients taking apremilast achieved 75% or greater reduction from baseline Psoriasis Area and Severity Index score (PASI-75) (33.1%) versus placebo (5.3%, P < .0001; primary end point). Most (61.0%) patients rerandomized to apremilast at week 32 achieved PASI-75 at week 52 versus 11.7% rerandomized to placebo. Of patients rerandomized to apremilast at week 32, mean percentage change from baseline PASI score was -88% to -81% (weeks 32-52). During the placebo-controlled period, 55.7% and 69.3% of patients randomized to placebo and apremilast, respectively, had 1 or more adverse events. Most adverse events were mild/moderate in severity. No new significant adverse events emerged with continued apremilast exposure versus the placebo-controlled period. LIMITATIONS: Data were limited to 52 weeks and may not generalize to nonplaque psoriasis. CONCLUSIONS: Apremilast was effective in moderate to severe plaque psoriasis.

Definitions and outcome measures for mucous membrane pemphigoid: recommendations of an international panel of experts.

Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index.

Psoriasis disease severity affects patient satisfaction with treatment.

BACKGROUND: Patients with psoriasis are often dissatisfied with available treatments, but contributing factors are not well defined. OBJECTIVE: Examine relationships between psoriasis severity, patient characteristics, and treatment satisfaction. METHODS: Patients with psoriasis were classified into mild and moderate-to-severe groups based on self-reported data. Demographics, comorbidities, symptoms, and multiple treatment satisfaction outcomes were compared between groups. Predictors of patient satisfaction with treatment were examined using linear regression models. RESULTS: The analyses included 773 patients (407 mild; 366 moderate-to-severe). The percentage of patients reporting satisfaction with treatment was low overall, ranging from 8.6% to 61.7% for the mild and 13.9% to 49.5% for the moderate-to-severe group. Satisfaction among biologics users was also low (≤53%; 50% of satisfaction rates <40%). Regression results consistently showed greater dissatisfaction with current treatment among moderately to severely affected patients. CONCLUSION: Many psoriasis patients were dissatisfied with their treatment; moderate-to-severe patients expressed significantly less satisfaction than mild patients.

Research gaps in psoriasis: opportunities for future studies.

Over the past 2 decades, considerable progress has been made to further elucidate the complex pathogenesis of psoriasis, facilitating the development of a new armamentarium of more effective, targeted therapies. Despite these important advances, substantial deficits remain in our understanding of psoriasis and its treatment, necessitating further research in many areas. In the sixth section of the American Academy of Dermatology Psoriasis Guidelines of Care, gaps in research and care were identified. We discuss the most important gaps in research that currently exist and make suggestions for studies that should be performed to address these deficits. These encompass both basic science and clinical research studies, including large, prospective epidemiologic studies to determine the true prevalence and natural history of psoriasis; further molecular studies in patients with psoriatic and psoriatic arthritis to understand the function of psoriasis susceptibility genes and to identify novel therapeutic targets; studies to examine the role of environmental factors in the development of psoriasis; further investigation of the relationship between psoriasis and cardiometabolic disease; studies that examine the role of adjunctive therapies such as psychological interventions in appropriate patient groups; and finally, studies to identify biomarkers of disease severity and treatment response to optimize patient therapy.

Deucravacitinib onset of action and maintenance of response in phase 3 plaque psoriasis trials.

AIM: In the global phase 3 POETYK PSO-1 and PSO-2 trials, significantly greater proportions of deucravacitinib-treated patients met the coprimary endpoints (PASI 75, sPGA 0/1) at Week 16 versus placebo or apremilast-treated patients. This analysis evaluated onset of action and maintenance of response in patients randomized to deucravacitinib and placebo only. METHODS: Adults with moderate to severe plaque psoriasis at baseline were randomized 1:2:1 to oral placebo, deucravacitinib, or apremilast. Onset of action was determined through changes from baseline in mean PASI, BSA, BSA × sPGA, and DLQI. Maintenance of response was assessed using PASI 75, PASI 90, PASI 100, sPGA 0/1, and sPGA 0 response rates through Week 52 in patients who were treated continuously with deucravacitinib, crossed over from placebo to deucravacitinib at Week 16, or received deucravacitinib and achieved PASI 75 by Week 24. RESULTS: Deucravacitinib showed significantly higher increases in mean percent change from baseline in PASI versus placebo by Week 1. Significant improvement versus placebo was observed in all other efficacy measures by Week 8. Efficacy with deucravacitinib was maintained through Week 52. CONCLUSION: Deucravacitinib displayed efficacy as early as 1 week and clinical responses were maintained over 52 weeks in patients with moderate to severe plaque psoriasis.

The Efficacy and Safety of Bimekizumab for Plaque Psoriasis: An Expert Consensus Panel.

INTRODUCTION: Psoriasis is a chronic inflammatory condition affecting the skin, joints, and several other organ systems with significant disease burden. Bimekizumab is the first monoclonal antibody targeting both interleukin (IL)-17A and interleukin-17F and has demonstrated efficacy for treating moderate to severe psoriasis. Limited guidelines exist for incorporating this drug into clinical practice. The purpose of this study was for a panel of experts in psoriasis management to synthesize current literature and provide consensus statements with guidance on use of bimekizumab. METHODS: A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the use of bimekizumab for moderate to severe psoriasis and psoriatic arthritis. A panel of nine dermatologists with significant expertise in treatment of psoriasis gathered to review the articles and create consensus statements on this new medication. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using Strength of Recommendation Taxonomy criteria. RESULTS: The literature search produced 102 articles that met criteria. A thorough screening of the studies for relevance to the research question resulted in 19 articles. These were distributed to all panelists for review prior to a roundtable discussion. The panel unanimously voted to adopt 14 consensus statements and recommendations, 12 of which were given a strength of "A", one of which was given a strength of "B", and one of which was given a strength of "C". CONCLUSION: Bimekizumab results in rapid and long-lasting clinical improvement for patients with moderate to severe plaque psoriasis and psoriatic arthritis. It has demonstrated superior efficacy when compared to several other biologics. The safety profile is consistent with other biologics, except for an increased incidence of oropharyngeal candidiasis.

Circulating Monocytes Are Predictive and Responsive in Moderate-to-Severe Plaque Psoriasis Subjects Treated with Apremilast.

Monocytes play a critical role in the inflammation associated with psoriasis, and their abnormalities have been reported as biomarkers of cardiovascular event risk, a psoriasis comorbidity. Monocytic cells in chronic inflammatory disorders express elevated levels of cAMP phosphodiesterase. Restoring cAMP levels using the oral cAMP phosphodiesterase-4 inhibitor, apremilast, improves clinical outcomes for a subset of patients with psoriasis. We asked whether aberrant monocyte subsets or transcriptomic pathways can function as biomarkers of psoriasis endotypes that can predict enhanced clinical responses to cAMP phosphodiesterase inhibition. A 16-week open-label study of 22 patients with monocyte flow cytometric and transcriptomic analysis was performed. Subjects with elevated hyperadhesive monocyte doublets at baseline were more likely to be responders to apremilast (P < .0001); 82% of subjects with elevated hyperadhesive monocyte doublets achieved 50% reduction in PASI compared with 46% in those without elevated doublets. We observed a significant reduction in hyperadhesive monocyte-containing doublets and monocyte-platelet aggregates, suggesting an effect of apremilast on the adhesiveness of blood monocytes during chronic inflammation. Monocyte differentially expressed gene transcripts predictive of clinical response uncovered pharmacoendotypes with distinct patterns of nucleotide metabolism, energetics, and differentiation. Further study to understand the basis of drug responsiveness and to develop an apremilast psoriasis treatment algorithm using monocyte-refined gene expression is required to validate and become practical in clinical use, offering patients a test that personalizes their likelihood of clinical response.