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Background: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis. Objective: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis. Methods: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16. Results: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes. Conclusions: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52. Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018). Plain Language Summary: Atopic dermatitis, or eczema, is a condition that causes painful itchy dry skin, which is burdensome for patients and has a negative impact on quality of life. These symptoms frequently lead to disruption of daily activities such as school and work, decreased self-confidence, social isolation, anxiety, depression, and sleep disturbance. Symptoms of atopic dermatitis, such as itch and sleep disturbance, can only be assessed by patients. Therefore, it is important to consider patients' perceptions of their symptoms and the related impact on their quality of life, especially when evaluating treatment benefits. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. In two clinical trials (Measure Up 1 and Measure Up 2), we investigated how treatment with upadacitinib (15-mg or 30-mg dose) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis would impact their symptoms and quality of life over a 1-year period. We measured changes over time in patients' assessments of itch, pain, other skin-related symptoms, sleep, daily activities, emotional state, mental health, and overall quality of life. Patients treated with upadacitinib experienced improvements in symptoms of atopic dermatitis and quality of life within the first 1–2 weeks of treatment. These improvements continued to steadily increase in the following weeks and lasted through 1 year of treatment. In conclusion, once-daily treatment with upadacitinib 15 or 30 mg led to early and lasting improvements in the well-being of patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Itch is the most bothersome symptom reported by patients with psoriasis. Safe and effective treatments for psoriasis that also address itch are needed. Objectives: To report effects of roflumilast cream on itch-related outcomes from a Phase 2b trial. Methods: Adults with chronic plaque psoriasis were randomized to roflumilast 0.3%, roflumilast 0.15%, or vehicle once-daily for 12 weeks. Psoriasis severity was assessed via the Investigator Global Assessment (IGA; a 5-point scale assessing plaque thickening, scaling, and erythema ranging from 0 [clear] to 4 [severe]) and ≥ 2 on a modified Psoriasis Area and Severity Index (PASI-HD, which combines severity of lesions and area affected, ranging from 0 [no disease] to 72 [maximal disease], with the actual percentage of the anatomical area involved in those patients with < 10% of anatomical area involved [e.g., 0.1 for 1% to 0.9 for 9%]). Itch was evaluated via Worst Itch Numeric Rating Scale (WI-NRS), Psoriasis Symptom Diary (PSD) Items 1 (severity of itch) and 2 (bother of itch), and itch-related sleep loss NRS scores. Post hoc correlation analyses between WI-NRS and PASI, WI-NRS and itch-related sleep loss, and WI-NRS and DLQI were also performed. Results: Roflumilast-treated patients had significantly greater improvements than vehicle-treated patients in WI-NRS and PSD Items 1 and 2 beginning at Week 2 and in itch-related sleep loss Weeks 6 through 12. Among patients with baseline WI-NRS ≥ 6, significantly more patients achieved ≥ 4-point improvement with roflumilast than with vehicle as early as Week 2. Itch severity had low correlation with PASI while WI-NRS and IGA were not always aligned. Limitations: The first assessment was at 2 weeks, limiting the ability to assess early onset of itch response. Conclusion: Roflumilast cream improved itch and itch-related sleep loss associated with chronic plaque psoriasis. ClinicalTrials.gov identifier: NCT03638258. [ABSTRACT FROM AUTHOR]

Introduction: Patients with psoriasis (PsO) should adhere to and be persistent with treatment to maintain disease control. Patient support programs (PSPs) are useful to support patients with disease management. We aimed to understand the real-world patient profile and persistence of ixekizumab-initiating Canadian patients with moderate-to-severe PsO using PSP data. Methods: This retrospective observational study was conducted utilizing a Canadian PSP database (May 2016 to March 2020). Inclusion criteria were: age ≥ 18 years with moderate-to-severe PsO, initiated ixekizumab, enrolled in the PSP for ≥ 6 months, and provided informed consent. Psoriasis Area Severity Index (PASI), body surface area (BSA) involvement, and Dermatology Life Quality Index (DLQI) were collected at PSP entry. Adherence [using the proportion of days covered (PDC)] and persistence (using Kaplan–Meier curves) were assessed after 1-year and 2-year follow-ups. Differences in persistence between biologic-naïve and biologic-experienced patients were compared using Cox proportional hazards model after adjusting baseline parameters. Results: In total, 1891 ixekizumab-treated moderate-to-severe patients with PsO were included. The mean [standard deviation (SD)] age was 52.3 (13.3) years; 51.1% of patients were 45–65 years old and 61.4% were male. At baseline, the mean (SD) PASI score was 14.3 (8.1), the DLQI score was 16.5 (7.7), and BSA % was 17.4 (15.1). PsO lesions were commonly located on the hands (33.4%), face (28.6%), and feet (23.8%). Ixekizumab-treated patients were highly adherent [PDC ≥ 80%: 1-year (92.0%), 2-year (87.7%)] and persistent [1-year (90.4%), 2-year (85.6%)]. Biologic-naïve patients were more adherent (1-year, 94.6% versus 87.3%; 2-year, 90.3% versus 83.5%) than biologic-experienced patients. Significantly higher persistence in biologic-naïve versus biologic-experienced patients for 1-year (p < 0.01) and 2-year (p = 0.010) follow-up periods was observed after adjusting for baseline parameters. Conclusion: Patients with moderate-to-severe PsO overwhelmingly remained on ixekizumab treatment for more than 2 years while participating in a PSP. [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]

Introduction: An estimated 2–4% of Western populations are thought to have psoriasis, with a regional incidence ranging from 0.09% to 11.43%. Variance in estimates is a result of differences in study populations, methodology, regional differences, and definitions of disease. Reliable prevalence estimates of plaque psoriasis are challenging to establish. Further, the distribution of psoriasis severity in the population is unknown. This study aims to establish the utility of expert elicitation (EE) as a method for estimating unknown parameters in dermatology by (1) estimating the prevalence of psoriasis in the adult population, and (2) estimating previously unknown disease severity distribution. Methods: An expert panel of 11 Canadian dermatologists with demonstrated expertise in psoriasis was formed. A proof-of-concept EE exercise estimated psoriasis prevalence in the general population in Canada, followed by estimation of psoriasis disease severity distribution by body surface area (BSA). Expert estimates were consolidated using Bayesian methods to statistically model the data and represent uncertainty. Results: The median prevalence of psoriasis in the adult population using the Bayesian estimate was 3.0% (95% credibility interval, 2.7–3.3%), compared with the estimated mean prevalence of 3.4% (95% confidence interval, 2.2–4.9%). By EE, the estimated cumulative distribution of disease severity assessed by BSA suggests that approximately 50% of patients have a BSA of < 3% and 78% of patients have a BSA of < 10%, with only 2% having a BSA of > 50%. Conclusion: The EE approach resulted in prevalence estimates that had a narrow distribution and were consistent with published literature, supporting its value in dermatology as a complementary method to help guide decision-making in areas where evidence is scarce or uncertain. Plain Language Summary: Psoriasis is a common skin disease that affects 2–4% of the population. Prevalence estimates vary depending on factors such as study type and population studied. The distribution of disease severity (what proportion of patients have mild, moderate, or severe psoriasis) is not known. In this study, 11 dermatologists with expertise in psoriasis used an approach called expert elicitation to make educated guesses about prevalence and disease severity distribution in the real world. Using a statistical approach called Bayesian estimation, experts can represent the level of certainty in what they know and do not know and make inferences or assumptions about a population. Bayesian estimates are not based on the amount of data; rather, each datum contributes to a statistically meaningful result. The median prevalence of psoriasis in the adult population using the Bayesian estimate was 3.0%, which is in the expected range based on prior literature and supports the use of this expert elicitation method. This study provides the first expert estimate of disease severity distribution in the population assessed by body surface area affected by psoriasis. Approximately 50% of psoriasis patients have mild disease (< 3% body surface area involved) and 78% of patients have mild or moderate disease (< 10% body surface area involved). Only 2% of patients have more than 50% body surface area involved. This expert elicitation approach can be used to help guide decision-making in areas of dermatology where evidence is lacking or uncertain. [ABSTRACT FROM AUTHOR]

Oral abrocitinib 200 and 100 mg once daily provided short-term efficacy in a dose-dependent manner over 12 or 16 weeks in various age groups of patients with moderate-to-severe atopic dermatitis (AD). This study aims to evaluate the long-term efficacy of abrocitinib treatment for up to 96 weeks in adult patients with moderate-to-severe AD who enrolled in JADE EXTEND (NCT03422822). This planned interim analysis included adult patients from the JADE clinical trials MONO-1 (NCT03349060), MONO-2 (NCT03575871), COMPARE (NCT03720470) and DARE (NCT04345367) who subsequently enrolled into the ongoing phase 3 extension trial JADE EXTEND (data cutoff: September 25, 2021). Patients who were randomly assigned to abrocitinib 200 or 100 mg once daily in the qualifying trials continued to receive the same dose in JADE EXTEND with blinding maintained; those who received placebo were randomly assigned to abrocitinib 200 or 100 mg. All patients from JADE DARE received a known dose of abrocitinib 200 mg in JADE EXTEND. Patients previously randomly assigned to dupilumab in JADE DARE or JADE COMPARE were excluded from this analysis. Patients were grouped for analysis by age (18–50 years; >50 years) recorded at the screening visit of the respective qualifying trial. Assessments included the proportion of patients who achieved Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement from baseline, ≥75% and ≥90% improvement from baseline on the Eczema Area and Severity Index (EASI-75 and EASI-90), a score of <2 or a ≥4-point improvement from baseline in Peak Pruritus Numerical Rating Scale score (PP-NRS 0/1 or PP-NRS4), and a score of <2 on the Dermatology Life Quality Index (DLQI 0/1). Data (as observed values) were evaluated up to 96 weeks of abrocitinib treatment. A total of 1309 patients [18–50 years (n = 1046); >50 years (n = 263)] were analysed. At Week 16 of abrocitinib treatment, patients achieved improvements with abrocitinib 200 or 100 mg in a dose-dependent manner in both age groups for IGA 0/1 [18–50 years, 55% (abrocitinib 200 mg)/34% (abrocitinib 100 mg); >50 years, 56%/38%], EASI-75 (79%/61%; 76%/69%) and PP-NRS4 (70%/51%; 76%/61%). Similar dose-dependent responses in both age groups were observed for the high-threshold clinical, patient-reported and health-related quality of life (HRQoL) endpoints of EASI-90 [18–50 years, 54% (abrocitinib 200 mg)/33% (abrocitinib 100 mg); >50 years, 59%/40%], PP-NRS 0/1 (35%/25%; 54%/30%) and DLQI 0/1 (38%/23%; 47%/24%). Regardless of age and dose, substantial proportions of patients were observed with responses at Weeks 24, 48 and 96 of abrocitinib treatment. At Week 96, dose-dependent responses remained for the younger subgroup of patients (including for high-threshold responses). For the older subgroup, responses were less clearly dose-dependent from Week 48. At Week 96, responder proportions were as follows: for IGA 0/1: 18–50 years, 55% (abrocitinib 200 mg)/44% (abrocitinib 100 mg); >50 years, 58%/51%; for EASI-75: 85%/73%, 89%/86%; for PP-NRS4: 66%/54%; 80%/79%; and for the high-threshold endpoints of EASI-90: 58%/45%; 73%/58%; for PP-NRS 0/1: 38%/26%; 44%/54%; and for DLQI 0/1: 41%/32%; 48%/51%. Regardless of age, substantial proportions of adults achieved clinical and patient-reported endpoints (IGA 0/1, EASI-75 or PP-NRS4) after short-term treatment with either abrocitinib dose. Similar trends were observed for high-threshold clinical, patient-reported and HRQoL endpoints (EASI-90, PP-NRS 0/1 or DLQI 0/1). Dose-dependent efficacy was observed short-term regardless of age, and up to 96 weeks in patients aged 18–50 years. Responder proportions of patients aged >50 years were less clearly dose-dependent from Week 48 of abrocitinib treatment. These findings may be informative for patients and healthcare providers when making treatment decisions. Further data from the ongoing JADE EXTEND trial may provide greater precision for long-term efficacy estimates. [ABSTRACT FROM AUTHOR]

Accordingly, the specific references to these instruments should be deleted, and the sentence should read as follows:Furthermore, PSAAD was developed to meet regulatory guidance and to be included in product-labelling claims in the USA and Europe. However, these instruments, including the Peak Pruritus Numerical Rating Scale, have either accumulated sufficient evidence to meet regulatory guidance related to product-labelling claims and/or have since been recommended for use in clinical trials. The Discussion section of the original publication previously said:Furthermore, PSAAD was developed to meet regulatory guidance and - unlike POEM, Itch Numeric Rating Scale (v2.0), Skin Pain Numeric Rating Scale (v2.0b), and Peak Pruritus Numerical Rating Scale - to be included in product-labelling claims in the USA and Europe. [Extracted from the article]