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Background: Atopic dermatitis (AD), a relapsing, inflammatory skin disease, is associated with pruritus that can negatively affect patients' quality of life. Understanding the burden of AD is critical for informing and tailoring treatment and disease management to improve patient outcomes. This study characterized global treatment patterns and the clinical, psychosocial and economic burden of moderate‐to‐severe AD. Methods: MEASURE‐AD was a cross‐sectional 28‐country study in patients with physician‐confirmed moderate‐to‐severe AD who were either receiving or eligible for systemic therapy for AD. Patients ≥12 years were enrolled between December 2019 and December 2020 while attending routine office or clinic visit. Primary outcomes included Worst Pruritus Numeric Rating Scale (WP‐NRS; range: 0–10) and Dermatology Life Quality Index (DLQI; range: 0–30) and Children's DLQI (CDLQI; range: 0–30). Secondary outcomes included physician‐ and patient‐reported clinical, psychosocial and economic burden. Results: Of the 1591 patients enrolled, 1558 (1434 adults and 124 adolescents) fulfilled all patient selection criteria and were included in this analysis. Almost all patients (98.4%) in the total population were using AD medications and more than half (56%) were receiving systemic medication (15% systemic monotherapy). The most used systemic therapies were dupilumab (56.3%), systemic glucocorticoids (18.1%) and methotrexate (16.2%). Mean WP‐NRS was 5.3 in the total population, and most patients (≥55%) reported moderate‐to‐severe pruritus (WP‐NRS ≥4). Mean DLQI was 10.8 and mean CDLQI was 9.6. Secondary endpoints demonstrated substantial clinical, psychosocial, and economic burden of disease. Subgroup analysis demonstrated that patients receiving systemic therapy had lower disease burden than those not taking systemic medications. Conclusions: While systemic therapy lowers overall disease burden, patients with moderate‐to‐severe AD continue to have substantial multidimensional disease burden and uncontrolled disease. Overall, there is a need for effective disease management, including effective treatments that improve patients' psychosocial outcomes and reduce the economic burden of AD. [ABSTRACT FROM AUTHOR]

Psoriasis is a common chronic immune-mediated disease with many comorbidities and impacts on quality of life. Among the treatments for psoriasis, phosphodiesterase-4 (PDE4) inhibitors are emerging with expanding options. PDE4 inhibitors play a pivotal role in the inflammatory cascade by degrading cyclic adenosine monophosphate (cAMP), contributing to pro-inflammatory mediator production. Apremilast, an oral PDE4 inhibitor, is approved for psoriasis. While effective, its adverse effects can limit its utility. Roflumilast, a topical PDE4 inhibitor, was also recently approved for psoriasis and shows promise in clinical trials. Crisaborole, a PDE4 inhibitor approved for atopic dermatitis, has also been studied in psoriasis. This review summarizes evidence from randomized clinical trials regarding the efficacy and safety of PDE4 inhibitors in psoriasis treatment. By highlighting their potential benefits and limitations, this review provides valuable insights for clinicians and researchers aiming to optimize psoriasis management. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib efficacy by comorbidity status in patients with moderate‐to‐severe atopic dermatitis (AD) has not been previously assessed. This post hoc analysis evaluated the efficacy and safety of abrocitinib in patients with AD and allergic comorbidities. Methods: Data were pooled from patients who received abrocitinib 200 mg, 100 mg, or placebo in phase 2b (NCT02780167) and phase 3 (NCT03349060, NCT03575871) monotherapy trials. Patients with and without allergic comorbidities (allergic asthma, rhinitis, conjunctivitis, or food allergy) were evaluated for Investigator's Global Assessment (IGA) response (clear [0] or almost clear [1]), ≥75% improvement in the Eczema Area and Severity Index (EASI‐75), ≥4‐point improvement in Peak Pruritus Numerical Rating Scale (PP‐NRS4), and Dermatology Life Quality Index (DLQI) response (<2 with baseline score ≥2). Other outcomes were Patient‐Oriented Eczema Measure (POEM), SCORing Atopic Dermatitis (SCORAD), Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD), and treatment‐emergent adverse events (TEAEs). Results: Of 942 patients, 498 (53%) reported at least one allergic comorbidity (asthma only, 33%; conjunctivitis only or rhinitis only or both, 17%; food allergies only, 15%; >1 allergic comorbidity, 34%). Regardless of comorbidity status, from Week 2 to Week 12, higher percentages of patients treated with either abrocitinib dose achieved IGA 0/1, EASI‐75, PP‐NRS4, or DLQI 0/1 versus placebo‐treated patients. Changes from baseline in POEM, SCORAD, and PSAAD were greater with abrocitinib than with placebo in patients with and without allergic comorbidities. Most TEAEs were mild or moderate. Conclusions: Efficacy and safety data support abrocitinib use to manage AD in patients with or without allergic comorbidities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction/Background Vitiligo is a chronic autoimmune disease characterized by melanocyte destruction, leading to skin depigmentation. Limited data are available regarding the efficacy of long-term topical vitiligo treatment. In 2 randomized, double-blinded, vehicle-controlled phase 3 studies in adults and adolescents (aged ≥12 y) with nonsegmental vitiligo (TRuE-V1 [NCT04052425]; TRuE-V2 [NCT04057573]), ruxolitinib cream application resulted in statistically superior improvements in repigmentation versus vehicle in the primary and all key secondary endpoints at Week 24 and was well tolerated. In the open-label period of TRuE-V1/TRuE-V2 (Weeks 24-52) and the TRuE-V long-term extension (LTE; Weeks 52-104) study (NCT04530344), further improvements in facial and body repigmentation (as assessed by Vitiligo Area Scoring Index [VASI] responses) were observed through Week 104 among patients who continued to apply ruxolitinib cream. Objectives: In this pooled analysis, we evaluated shifts in facial and total body VASI (F-VASI/T-VASI) responses among patients with vitiligo who had limited or no repigmentation at Week 24 and who continued to apply ruxolitinib cream for an additional 80 weeks. Methods: In TRuE-V1/TRuE-V2, patients were randomized 2:1 to apply twice-daily 1.5% ruxolitinib cream or vehicle for 24 weeks, after which all patients could apply 1.5% ruxolitinib cream through Week 52. Patients who completed TRuE-V1/TRuE-V2 were eligible to enroll in the TRuE-V LTE. Patients who did not achieve ≥90% improvement in F-VASI at Week 52 continued to apply open-label 1.5% ruxolitinib cream until Week 104. Patients initially randomized to apply ruxolitinib cream who had <25% improvement from baseline in F-VASI or T-VASI at Week 24 and had non-missing VASI assessments at the evaluated time points were included in this analysis. Shifts in F-VASI and T-VASI were assessed among patients with no facial/body repigmentation or worsening depigmentation (≤0% improvement in F-VASI/T-VASI) and patients with limited facial/body repigmentation (>0%- <25% improvement in F-VASI/T-VASI) at Week 24. Results: Among patients with no facial repigmentation at Week 24, improvements in F-VASI at Weeks 52 and 104 were observed in 77.8% (49/63) and 97.1% (34/35) of patients, respectively. Among patients with limited facial repigmentation at Week 24, F-VASI improvements at Weeks 52 and 104 were observed in 64.0% (32/50) and 83.3% (30/36) of patients, respectively. Across both groups, 54.9% (39/71) of patients achieved =75% improvement from baseline in F-VASI (F-VASI75) at Week 104. Among those with no body repigmentation at Week 24, T-VASI improvements at Weeks 52 and 104 were observed in 79.6% (39/49) and 93.3% (28/30) of patients, respectively. For those with limited body repigmentation at Week 24, T-VASI improvements at Weeks 52 and 104 were observed in 64.5% (80/124) and 81.6% (62/76) of patients, respectively. Across both groups who had <25% improvement in total body repigmentation at Week 24, 50.0% (53/106) of patients achieved ≥50% improvement in T-VASI (T-VASI50) at Week 104. Conclusions: In the TRuE-V studies, ruxolitinib cream application for an additional 80 weeks resulted in improved repigmentation among patients with nonsegmental vitiligo who had limited or no repigmentation at Week 24. These 2-year TRuE-V results highlight the importance of prolonged treatment in patients with vitiligo, even when minimal or no repigmentation is achieved after 6 months of treatment. [ABSTRACT FROM AUTHOR]

Background Scalp psoriasis affects most patients with psoriasis, but it can be difficult to treat. Objectives To evaluate the efficacy and safety of once-daily roflumilast foam 0.3% on scalp and body psoriasis. Methods In a phase IIb randomized controlled trial, adults and adolescents aged ≥ 12 years with scalp and body psoriasis were randomized (2 : 1) to roflumilast foam 0.3% or vehicle for 8 weeks. The primary efficacy endpoint was scalp Investigator Global Assessment (S-IGA) success (score of 'clear' or 'almost clear' plus ≥ 2-grade improvement from baseline) at week 8. Safety and tolerability were also evaluated. Results Significantly more roflumilast-treated patients (59.1%) than vehicle-treated patients (11.4%) achieved S-IGA success at week 8 (P < 0.001); differences favoured roflumilast as early as the first postbaseline visit at week 2 (P < 0.001). Significant improvements were also seen for secondary endpoints, including body IGA success, Scalp Itch Numeric Rating Scale and the Psoriasis Scalp Severity Index. The safety of roflumilast was generally similar to vehicle. Patients treated with roflumilast experienced low rates of treatment-emergent adverse events (AEs), with few discontinuations due to an AE. Few patients with skin of colour (11%) and few adolescents (0.7%) were included. Conclusions The results support the further development of roflumilast foam for treating scalp and body psoriasis. [ABSTRACT FROM AUTHOR]

Abrocitinib is a Janus kinase (JAK) 1-selective inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD). Although specific dose recommendations for abrocitinib vary across regional product labels, abrocitinib 100 mg once daily is recommended as a starting and maintenance dose. This review summarizes the efficacy and safety of abrocitinib 100 mg once daily for patients with moderate-to-severe AD based on data from the pivotal phase 3 studies of the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) clinical program, JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE COMPARE (NCT03720470), JADE TEEN (NCT03796676), and JADE REGIMEN (NCT03627767). Preliminary long-term efficacy and safety data are also summarized from the long-term extension study JADE EXTEND (NCT03422822). Expert opinion on use of abrocitinib 100 mg once daily in clinical practice is provided. In addition to efficacy, the decision to use abrocitinib for the treatment of AD should allow for individual patient factors such as age, comorbidities, previous therapy, quality of life, and treatment tolerability, and involve shared decision-making between the patient and clinician. [ABSTRACT FROM AUTHOR]

Background/Objectives: Topical clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel (IDP-126) is the first fixed-dose triple-combination formulation in development for acne. This post hoc analysis investigated efficacy and safety of IDP-126 in children and adolescents with moderate-to-severe acne. Methods: In a randomized, double-blind phase 2 study (NCT03170388), participants ≥9 years of age with moderate-to-severe acne were eligible for randomization (1:1:1:1:1) to once-daily IDP-126, one of three dyad combination gels, or vehicle gel for 12 weeks. This post hoc analysis of pediatric participants (n = 394) included children and adolescents up to 17 years of age. Assessments included treatment success, inflammatory/ noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. Results: At Week 12, treatment success rates were significantly greater with IDP126 (55.8%) than with vehicle (5.7%; p < .001) or any of the dyad combinations (range: 30.8%–33.9%; p < .01, all). Lesion reductions with IDP-126 were also significantly greater than with vehicle (inflammatory: 78.3% vs. 45.1%; noninflammatory: 70.0% vs. 37.6%; p < .001, both) and 9.2%–16.6% greater than with any of the dyad combinations. Increases (improvements) from baseline in Acne-QoL domain scores were generally greater with IDP-126 than in any other treatment group. The most common treatment-related TEAEs across treatment groups were application site pain and dryness. Most treatment-related TEAEs were of mild-to-moderate severity. Conclusion: IDP-126 gel—a novel fixed-dose, triple-combination topical formulation for acne—demonstrated superior efficacy to vehicle and three dyad component gels and was well tolerated in children and adolescents with moderate-to-severe acne. [ABSTRACT FROM AUTHOR]

There is a need for clear criteria to guide treatment decisions and disease management in patients with atopic dermatitis (AD). The recently developed minimal disease activity (MDA) concept aims to optimize AD management through shared decision-making between patients and clinicians in a treat-to-target approach, and is based on consensus recommendations from 87 physicians and insights from 88 patients globally.This study aims to evaluate how achieving MDA affects outcomes in patients with AD. Observed-case data from three phase 3 clinical trials involving adolescents and adults with moderate-to-severe AD were integrated and analysed (NCT03568318, NCT03569293 and NCT03607422). The MDA criteria were applied to clinician-reported measures [Eczema Area and Severity Index (EASI), SCORing of Atopic Dermatitis, validated Investigator Global Assessment, and body surface area] and patient-reported measures [Worst Pruritus Numerical Rating Scale (WP-NRS), Patient-Oriented Eczema Measure, Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain score, Atopic Dermatitis Impact Scale (ADerm-IS) Sleep disturbance score, Hospital Anxiety and Depression Scale and Dermatology Life Quality Index]. Patients were stratified into three mutually exclusive groups by achievement of treatment targets per measurement at week 16: (i) achieving the optimal target (i.e. MDA) criteria [e.g. EASI improvement ≥90% (EASI 90); WP-NRS ≤1], (ii) achieving the moderate but not optimal target criteria [e.g. EASI improvement ≥75% and <90%; WP-NRS improvement (reduction) ≥4 and WP-NRS >1] and (iii) not achieving either target criteria. Among the stratified target groups (optimal, moderate and neither), patients' symptoms, quality of life, work productivity and treatment satisfaction were assessed based on achieving meaningful clinically important differences in ADerm-SS 7-item total symptom score (ADerm-SS TSS-7; improvement ≥28), ADerm-IS Daily Activities score (improvement ≥14), ADerm-IS Emotional State score (improvement ≥11), percentage-point improvement in Work Productivity and Activity Impairment (WPAI) Overall Work Productivity score and proportion reporting Patient Global Impressions of Treatment of 'Extremely/Very Satisfied'. Stratified target groups were compared with a chi-squared or t -test for categorical or continuous variables, respectively, based on observed data. This analysis included 2392 patients. Patients in the optimal target (MDA) group based on EASI (EASI 90) vs. those in the moderate or neither target group had a higher proportion reporting meaningful improvements in ADerm-SS TSS-7 (optimal = 82.6% vs. moderate = 56.8% or neither = 27.4%; P < 0.001 for both comparisons), ADerm-IS Daily Activities (87.2% vs. 66.2% or 39.9%; both P < 0.001) and ADerm-IS Emotional State (86.1% vs. 67.1% or 36.8%; both P < 0.001); a greater percentage-point improvement in WPAI Overall Work Productivity (36.8% vs. 29.2% or 16.6%; both P < 0.01); and a higher proportion reporting being very/extremely satisfied with treatment (73.5% vs. 54.0% or 23.5%; both P < 0.001). Patients in the optimal target (MDA) group based on itch (WP-NRS ≤1) vs. those in the moderate or neither target group had a higher proportion reporting meaningful improvements in ADerm-SS TSS-7 (94.3% vs. 79.7% or 19.1%; both P < 0.001), ADerm-IS Daily Activities (97.3% vs. 84.7% or 33.6%; both P < 0.001) and ADerm-IS Emotional State (94.5% vs. 84.5% or 31.7%; both P < 0.001); a greater percentage-point improvement in WPAI Overall Work Productivity [39.7% vs. 35.2% (not significant) or 14.6% (P < 0.001)]; and a higher proportion reporting being very/extremely satisfied with treatment (79.7% vs. 60.5% or 26.8%; both P < 0.001). Trends were similar in other clinician- and patient-reported measures, with patients who achieved MDA generally reporting better outcomes. Achieving MDA from both a clinician and patient perspective was generally associated with greater improvements in AD symptoms, daily activities, emotional state, work productivity and higher satisfaction. These results demonstrate the value of achieving MDA and support implementing MDA in clinical practice to help improve the current standard of AD care. [ABSTRACT FROM AUTHOR]

Treat‐to‐target (T2T) recommendations for the use of systemic therapies (including biologics) in patients with moderate‐to‐severe plaque psoriasis have been published by a few groups of experts worldwide. However, there remains considerable variability in the choice of target severity measure and timing of milestones. To develop consensus recommendations for implementing T2T strategies for the management of moderate‐to‐severe plaque psoriasis using biologics. An expert group of Canadian dermatologists (the Committee) convened to develop a T2T consensus statement. They held a virtual meeting during which a preliminary set of criteria was created. These criteria were then reviewed, modified, and recirculated until unanimous agreement was achieved. The Committee agreed that defining treatment target is multidimensional and should reflect objective severity measures, as well as clinician and patient‐reported outcomes. The Committee unanimously proposes a criterion‐based system for determining the achievement of treatment target. The proposed T2T approach presented here provides a clinical framework for defining treatment success, measuring progress toward treatment success, recognizing when treatment modifications are warranted, and recommending treatment optimization strategies. [ABSTRACT FROM AUTHOR]

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

Background Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, and dupilumab, an anti-interleukin 4 receptor a monoclonal antibody, have been approved for the treatment of patients with moderate-to-severe atopic dermatitis (AD). The efficacy of abrocitinib and dupilumab as monotherapy or in combination with medicated topical therapy has been demonstrated in multiple phase 3 clinical trials. As is the case with many therapies, some patients with AD may need to discontinue treatment with dupilumab (due to inadequate efficacy, intolerable side-effects, patient choice, or other reasons) and switch to other systemic therapies. Objective To evaluate the long-term treatment response in patients with moderate-to-severe AD who switched from dupilumab to abrocitinib, as it is valuable information for prescribers and patients to consider when making treatment decisions. Methods: The phase 3 JADE COMPARE trial (NCT03720470) evaluated the efficacy of abrocitinib (100 mg or 200 mg once daily) and dupilumab (300 mg every 2 weeks) versus placebo in combination with topical medicated therapy in patients with moderate-to-severe AD through week 16. After a wash-out period, dupilumab-treated patients from JADE COMPARE who enrolled in the ongoing long-term extension trial JADE EXTEND (NCT03422822; clinical data cutoff: Sept 25, 2021) were randomised to receive double-blinded treatment with abrocitinib 100 mg or 200 mg. This post hoc analysis evaluated the response to dupilumab through week 16 in JADE COMPARE and thereafter in JADE EXTEND following a switch to abrocitinib through week 104 of total treatment duration/week 84 of abrocitinib treatment. Assessments included Investigator's Global Assessment score of 0 (clear) or 1 (almost clear) with a =2-point improvement from baseline (IGA 0/1), =75% or =90% improvement from baseline in Eczema Area and Severity Index (EASI-75 or EASI-90), =4-point improvement from baseline in Peak Pruritus Numerical Rating Scale score (PP-NRS4; PP-NRS used with permission from Regeneron Pharmaceuticals, Inc., and Sanofi), and a PP-NRS score of 0 or 1 (PP-NRS 0/1). JADE EXTEND data are presented as observed; patients with missing data at a visit were excluded. Analyses included both dupilumab responders and non-responders. Results: Overall, 242 patients were treated with dupilumab in JADE COMPARE (mean age: 37 years; IGA score 4: 33%). Of those, 203 enrolled in JADE EXTEND and received abrocitinib 200 mg (n=73) or abrocitinib 100 mg (n=130). After 16 weeks of treatment with dupilumab in JADE COMPARE, the proportion of responders was 39% for IGA 0/1, 66% for EASI-75, 39% for EASI-90, 57% for PP-NRS4, and 24% for PP-NRS 0/1. As early as 2 weeks after switching to abrocitinib (200 mg/100 mg) in JADE EXTEND, the proportion of responders was observed to increase in a dose-dependent manner, respectively, for IGA 0/1 (61%; 51%), EASI-75 (90%; 85%), EASI-90 (60%; 54%), PP-NRS4 (81%; 72%), and PP-NRS 0/1 (47%; 37%). Long-term efficacy was observed out to week 84 (Figure). Conclusions: In patients with moderate-to-severe AD who received prior treatment with dupilumab, switching to abrocitinib resulted in dose-dependent increases in the proportion of responders as early as week 2 after treatment with abrocitinib. This efficacy continued to be observed long-term through week 84 of abrocitinib treatment. [ABSTRACT FROM AUTHOR]

Background Skin pain is a common and burdensome symptom of atopic dermatitis (AD), and its severity increases with disease progression. The Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) is a validated 11-item patient-reported instrument developed in accordance with regulatory agency guidance for assessment of the daily symptoms of patients with AD, including skin pain. Objective To establish content validity and evaluate the psychometric properties of the skin pain numerical rating scale (NRS) item of the PSAAD. Methods: The skin pain NRS is a single-item measure from the PSAAD and is used to assess skin pain severity over the past 24 hours with the question "How painful was your skin over the past 24 hours?" on a 10-point scale from 0 (not painful) to 10 (extremely painful). A qualitative validation analysis consisting of concept elicitation (CE) interviews; electronic completion of the PSAAD measure, including the skin pain NRS; and cognitive debriefing (CD) interviews was conducted for adults and adolescents with mild-to-severe AD. Evaluation of psychometric properties of the skin pain NRS--including test-retest reliability, estimation of meaningful within-patient change (MWPC), known-group validity, ability to detect change, construct validity, quality of completion, and ceiling and floor effects--was conducted based on a post hoc qualitative and quantitative analysis of pooled data, with skin pain NRS as part of the PSAAD in the abrocitinib monotherapy phase 3 trials JADE MONO-1 (NCT03349060) and JADE MONO-2 (NCT03575871). Data from patients (≥12 years of age) with moderate-to-severe AD were pooled across all treatment arms. Results: Among 30 CE interviews (adolescents [12-17 years], n=15; adults [≥18 years], n=15) conducted over 2 rounds of testing, 20 of 30 (67%) patients reported skin pain. During CD interviews (n=30), 100% of patients interpreted the skin pain NRS item as intended, and 73% reported it as relevant. The psychometric validation analysis included 736 patients (JADE MONO-1, N=347; JADE MONO-2, N=389). The test-retest reliability of the skin pain NRS was evidenced by large intraclass correlation coefficients (ICC; 0.76 and 0.72 in JADE MONO-1 and MONO-2, respectively) for a single daily skin pain score, which increased to 0.93 and 0.91 for a measurement averaging at least 4 scores per week. Convergent validity was demonstrated by correlations between skin pain and other clinician- and patient-reported AD measures (median correlation >0.4 starting at week 4). The skin pain NRS distinguished between "clear" and "severe" disease severity groups, assessed using the Patient Global Assessment (PtGA) and Investigator's Global Assessment (IGA) as continuous and categorical anchors (P<0.0001); differences were also significant among other disease severity groups using the PtGA and IGA as continuous anchors (P<0.0001). Based on the PtGA and IGA anchor analysis, the estimated MWPC was 1.9 and ranged from 2.7 to 3.9 points using the empirical cumulative distribution function analysis. Ability to detect change was demonstrated by linear relationships between disease severity measures and skin pain scores (correlation of ≥0.5 between the skin pain NRS and the PtGA). More than 90% of patients provided at least 4 daily skin pain scores each week. No floor or ceiling effects were observed. Conclusions: The qualitative and quantitative data from initial PSAAD development and psychometric evaluation of the skin pain NRS from the PSAAD support its content validity, reliability, construct validity, and ability to detect change. These findings corroborate the 4-point improvement in skin pain as the adequate and meaningful cut-off to define a skin pain responder in JADE MONO-1 and MONO-2. [ABSTRACT FROM AUTHOR]

Introduction & Objectives: Upadacitinib (UPA) 15 and 30 mg once daily is approved for moderate to severe atopic dermatitis (AD) in several jurisdictions, including the European Union, Japan, Canada, and the United States, with indication/posology differences. Clinical studies have documented the safety and efficacy of UPA; however, real-world data on UPA are limited. The AD-VISE study objective is to characterize the real-world utilization patterns and effectiveness of UPA 15 and 30 mg in adults and adolescents with AD in clinical practice. Materials & Methods: AD-VISE is an ongoing observational, prospective, multicountry study to assess the use of UPA in routine clinical practice for 2 years. Adult and adolescent patients (pts) receiving UPA for AD are being enrolled. Primary effectiveness outcome measures included validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) 0/1 at month 4. Other outcome measures included Eczema Area and Severity Index (EASI), Worst Pruritus Numeric Rating Scale (WP-NRS), and Dermatology Life Quality Index (DLQI). This interim analysis (data cutoff February 27, 2023) reports baseline data and 2- and 4-month effectiveness data. Effectiveness analyses included pts that were enrolled at least 4 months by the data cutoff date or discontinued from the study; non-responder imputation with multiple imputation (NRI-MI) was used. Results: Baseline analyses included 267 pts, of whom 21 (7.9%) were adolescents; effectiveness analyses included 209 patients (NRI-MI). Overall, 155 (58.1%) pts started on UPA 15 mg and 112 (41.9%) started on UPA 30 mg. Most pts in this analysis were from Canada (56.2%), followed by Russia (10.9%) and Australia (8.6%). Mean (SD) UPA exposure was 218.8 (±117.6) days; 5.6% of pts discontinued UPA and 3.7% discontinued the study. The most common reason for starting on UPA 15 mg was attempting lowest possible effective dose (42.9%) and on 30 mg, high disease burden/severity of skin symptoms (35.2%). More pts starting UPA 30 mg vs 15 mg were between 18 to <65 years old (96.4% vs 76.1%), male (61.6% vs 51.0%), had severe AD (vIGA-AD score 4: 53.6% vs 46.3%), had prurigo nodules (30.6% vs 18.4%), asthma (45.5% vs 24.5%), and prior biologic systemic therapy use (16.1% vs 10.3%). More than half of the pts (51.2%) achieved vIGA-AD 0/1 at month 2, and this proportion increased to 61.3% at month 4. Similarly, rate of achieving EASI 90 (month 2: 46.9%; month 4: 57.2%) and DLQI 0/1 (month 2: 35.1%; month 4: 41.3%) increased, whereas rates were maintained for =4-point WP-NRS improvement (month 2: 68.1%; month 4: 69.3%). Similar results were observed with other endpoints. Conclusion: Initial findings from the AD-VISE study, the largest study to report multicountry real-world data on UPA treatment patterns and effectiveness in AD, suggest that most pts achieved clear/almost clear skin and clinically meaningful itch improvement by month 4. Because this is a real-world observational study, it was expected that physicians start with UPA dose per local label. The main reason for starting UPA 30 mg was high disease burden/severity of skin symptoms, whereas 15 mg was started to attempt the lowest possible effective dose. More pts starting UPA 30 mg vs 15 mg were adults, male, and had prior biologic systemic therapy use. [ABSTRACT FROM AUTHOR]

Background: Real-world knowledge of the burden of hidradenitis suppurativa (HS) on patients remains limited. Objectives: To measure the impact of adalimumab on moderate-to-severe HS patients' health-related quality of life (HRQoL) and work productivity. Methods: In 23 Canadian centres, 138 adults with moderate-to-severe HS requiring a change in ongoing therapy were treated with adalimumab for up to 52 weeks as per the physician's practice. Patient-reported outcome measures (PROMs) were obtained at baseline, weeks 24 and 52 to measure overall HRQoL, HS severity, levels of anxiety and depression, impact and symptoms of HS, work productivity and activity impairment. A post-hoc analysis further explored the PROMs by abscess and inflammatory nodule (AN) count at baseline (≤5, low; 6–10, medium; ≥11, high). Results: From baseline to weeks 24 and 52, all PRO overall scores improved significantly (P ≤.0023). The number of patients reporting "good disease control" and "complete disease control" increased from 9.7% to 66.4% over 52 weeks. The score in Health Utility Index Mark 3 (HUI3) pain attribute meaningfully decreased over 52 weeks (mean difference ≥.05). The HS symptoms skin "tenderness" and "itchiness" improved the most. Work productivity loss and activity impairment improved by approximately 20% over 52 weeks. Disease burden improved more in 24 week responders with low and medium AN counts at baseline than in those with high AN count or in 24 week nonresponders. Conclusion: At week 24 and maintained at week 52 in a real-world setting, adalimumab meaningfully improved HRQoL, work productivity, and activity impairment in moderate-to-severe HS patients. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic heterogeneous condition characterized by erythematous, pruritic, and inflamed skin. Janus kinase (JAK) inhibitors are a new class of drugs that target proteins in the Janus kinase‐signal transducer and activator of transcription (JAK‐STAT) pathway. These drugs can be administered orally or topically to inhibit signaling of the JAK‐STAT pathway and minimize the production of proinflammatory cytokines. The efficacy and safety of JAK inhibitors have been investigated in phase 2 and 3 clinical trials for AD. The safety of new medications, which are immunosuppressive by nature, is of utmost concern for the prescriber and patient alike. Herein we summarize the safety results of clinical trials using oral abrocitinib, upadacitinib, and baricitinib, as well as topical ruxolitinib and delgocitinib for the treatment of AD. The most prevalent (2–5% occurrence rate) treatment‐emergent adverse events from oral JAK inhibitor use in AD were nausea, upper respiratory tract infection, headache, herpes zoster, herpes simplex, acne, increased blood creatine phosphokinase levels, and decreased platelet counts. Topical JAK inhibitors were not associated with systemic effects. All studies reported that JAK inhibitors were well tolerated in patients with AD in comparison with the control group. While the use of JAK inhibitors in patients suffering from AD is very promising, trials reported to date are of short duration (maximum 16 weeks), and more information on the long‐term safety of these novel agents is required. [ABSTRACT FROM AUTHOR]

Celiac disease is a multifactorial, inflammatory disorder initiated and sustained by the ingestion of gluten. Occurring across a broad population, the intestinal and extraintestinal manifestations of celiac disease are variable in severity and may be nonspecific in presentation. Given that environmental, genetic, and immune factors involved in the pathogenesis of celiac disease that the digestive tract and skin share many characteristics, and with a prevalence of 0.5–1% in most populations, it is reasonable to consider varying presentations of skin conditions that are linked with celiac disease. The association between celiac disease and skin conditions has been discussed earlier, but new studies have emerged suggesting cutaneous involvement in addition to dermatitis herpetiformis. We review the current literature identifying the relationship and potential mechanisms between celiac disease and various skin conditions. [ABSTRACT FROM AUTHOR]

Real‐world and long‐term data on biologic treatment changes – including switching, discontinuation, dose escalation, and interval change (both increasing and decreasing) – are required to understand treatment patterns for psoriasis (PsO) in Canada. The study objectives were to evaluate the time to first biologic treatment change and to document these changes in Canadian patients with moderate‐to‐severe chronic plaque PsO. Charts from 13 Canadian sites were queried retrospectively (2005–2019); a period covering all biologic classes commonly used for PsO in Canada. Included were patients diagnosed with, and currently using biologics for, moderate‐to‐severe chronic plaque PsO. Time to first treatment change, nature of treatment change, number of lines of treatment, proportion of patients on each drug, and drug survival were collected. Based on 1149 medical charts, adalimumab had the longest time to first treatment change (49.3 months; 95% confidence interval, 37.4–67.4). Approximately half of the patients had a treatment change, and nearly 75% of these changes were either an interval change or a biologic switch. Lack of efficacy was the most prevalent primary reason for biologic switch (67.3%), whereas 6.7% of patients switched due to adverse events. Drug survival for etanercept and infliximab was approximately twice as long for patients who had dose optimization (i.e., dose escalation or interval change) than patients without dose optimization. The survival curve of adalimumab was similar to the one of ustekinumab after 48 months of treatment, showing approximately 60% of patients remaining on treatment after 132 months, with or without dose optimization. Assessing treatment patterns of all commonly used biologics for moderate‐to‐severe chronic plaque PsO in Canada between 2005 and 2019 showed that approximately half of the patients required a treatment change (mainly interval change or biologic switch) while the other half remained on treatment. [ABSTRACT FROM AUTHOR]

The effects of consuming a soy protein isolate beverage powder (60 g/d for 28 d) vs. a casein supplement was evaluated in 20 male subjects who were randomly allocated into the two groups. A dramatic rise in plasma isoflavone concentrations was observed after supplementation in the soy protein group, the levels reaching 907 [+ or -] 245 nmol/L for genistein (a 110-fold increase) and 498 [+ or -] 102 nmol/L for daidzein (a 150-fold increase) as measured by isotope dilution gas chromatography - mass spectrometry. These concentrations are higher than previously reported for the plasma of Japanese subjects consuming a traditional diet (276 nmol/L and 107 nmol/L, respectively). No significant differences in collagen- or 9, 11-dideoxy-11[Alpha], 9[Alpha]-epoxymethanoprostaglandin [F.sub.2[Alpha]] (U46619)-induced platelet aggregation were observed in platelet-rich plasma from the two groups; the increase in plasma isoflavonoids from soy protein supplementation is not sufficient to significantly inhibit platelet aggregation ex vivo. Similarly, plasma total and HDL-cholesterol were not affected by protein supplementation, possibly because the men were normocholesterolemic at entry. Analysis of plasma phospholipid polyunsaturated fatty acid composition showed no differences between soy protein and casein supplementation. Previous investigations reported a significant alteration in fatty acid status in animals fed soy protein relative to those fed casein. The present studies indicate that although soy protein supplementation to a typical Western diet can increase plasma concentrations of isoflavones, this may not necessarily be sufficient to counter heart disease risk factors such as high plasma cholesterol and platelet aggregation. J. Nutr. 126: 2000-2006, 1996. INDEXING KEY WORDS: humans; soy protein; isoflavones; platelet; plasma cholesterol

Dear Editor, Despite recent advances, the effects of immune-modulating biologic therapies on the clinical course of COVID-19 remains unclear ([1]). Our findings also corroborate similar studies on SARS-CoV-2 infections in patients with atopic diseases undergoing dupilumab treatment. From the Italian-based DA-COVID-19 registry, Chiricozzi et al. noted that 15 of 1576 patients (0.9%) with AD on dupilumab, either monotherapy or combined therapy, had SARS-CoV-2 infection. [Extracted from the article]

In VOYAGE 1 (NCT02207231) and VOYAGE 2 (NCT02207244), guselkumab, an interleukin-23 blocker, was safe and effective in patients with moderate-to-severe plaque psoriasis. Patients who self-identified as Hispanic (n = 117) or non-Hispanic (n = 1686) were randomized to guselkumab, placebo, or adalimumab. Efficacy assessments included Psoriasis Area and Severity Index (PASI), Investigator's Global Assessment (IGA), and Dermatology Life Quality Index (DLQI). At week 16, treatment differences for guselkumab versus placebo in the Hispanic and non-Hispanic populations were 67.4 (95% confidence interval 50.4, 84.4) and 77.2 (73.5, 80.8) percentage points for IGA 0/1 and 59.2 (41.9, 76.4) and 69.2 (65.7, 72.7) percentage points for PASI 90, respectively. Treatment differences for guselkumab versus adalimumab were 25.9 (6.5, 45.3) and 17.5 (12.8, 22.3) percentage points for IGA 0/1 and 21.4 (–0.1, 42.9) and 23.5 (18.2, 28.9) percentage points for PASI 90, respectively. Week 24 results were similar. Adverse event frequency was greater in adalimumab- versus guselkumab-treated patients in the Hispanic population only through weeks 16 and 28. In both populations, DLQI 0/1 responses were greater in guselkumab-treated versus placebo- and adalimumab-treated patients at week 16 and versus adalimumab-treated patients at week 24. Guselkumab safety and efficacy were consistent between Hispanic and non-Hispanic populations. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare, chronic skin disease, characterized by widespread pustules and erythema, often accompanied with systemic signs and symptoms. GPP flares occur episodically but may be protracted. Left untreated, GPP can be life‐threatening. Despite being first reported over 100 years ago, definitions and diagnostic criteria for GPP have been inconsistent and varied due, in part, to its rarity and a limited understanding of its pathogenesis. As such, many patients with GPP face delays in diagnosis and subsequent treatment. This manuscript aims to increase the recognition of GPP and provide foundational considerations to aid in the definition and diagnosis of this disease. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic immune-mediated inflammatory disorder. Phosphodiesterase-4 (PDE-4) is an enzyme that mediates inflammatory responses and plays a role in psoriasis pathogenesis. PDE-4 degrades its substrate cyclic adenosine monophosphate (cAMP) to adenosine monophosphate (AMP), which subsequently leads to the production of pro-inflammatory mediators. Inhibitors of PDE-4 work by blocking the degradation of cAMP, which leads to a reduction in inflammation. Apremilast is the only approved oral PDE-4 inhibitor for the treatment of psoriasis. While it is effective for some patients, it may be limited by adverse effects in others. A topical PDE-4 inhibitor, roflumilast, is being investigated in psoriasis and showing promising results. Crisaborole, a topical PDE-4 inhibitor approved for use in atopic dermatitis, has also been investigated in psoriasis. This is an updated comprehensive review to summarize the currently available evidence for the PDE-4 inhibitors apremilast, roflumilast and crisaborole in the treatment of psoriasis, with a focus on data from randomized clinical trials. [ABSTRACT FROM AUTHOR]