Atopic Dermatitis Research Articles

Patient and Parent/Caregiver Satisfaction with Efficacy and Cosmetic Elegance of Tapinarof Cream 1% Once Daily in a Long-term Extension Trial in Adults and Children Down to Age 2 Years with Atopic Dermatitis

Introduction: Patients with atopic dermatitis (AD) report low satisfaction with currently available topical therapies. Satisfaction and patient preference are closely linked to treatment adherence, and understanding preferences may contribute to improving the quality of AD care and adherence. In the pivotal 8-week, phase 3 ADORING 1 and 2 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) demonstrated superior efficacy versus vehicle and was well tolerated in adults and children down to age 2 years with AD. We report Patient Satisfaction Questionnaire© (PSQ) results from ADORING 3, a 48-week, open-label extension trial. Methods: In ADORING 3, eligible patients from ADORING 1 and 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild AD, or moderate or severe AD, that did not meet inclusion criteria for ADORING 1 or 2, were followed for up to 48 weeks. The PSQ was completed at Week 48 or at early termination visit and assessed patient or parent/caregiver satisfaction with tapinarof efficacy, cosmetic elegance (look and feel of tapinarof cream), application ease, impact on daily life, and preference for tapinarof versus prior AD therapies. Patients aged ≥16 years self-completed the PSQ; parents/caregivers completed for children aged 2 to 15 years. Results: 505 patients or parents/caregivers completed the questionnaire. Respondents consistently reported high rates of satisfaction across all parameters. Most patients or parents/caregivers strongly agreed or agreed with PSQ questions assessing satisfaction with cosmetic elegance (91.5%), quick absorption (89.5%), application ease (97.6%), impact on daily life (94.3%), efficacy (92.3%), and confidence in tapinarof (92.7%). For patients or parents/caregivers who reported prior use of other topical therapies to treat AD, most strongly agreed or agreed that tapinarof was more effective (86.3%), easier to use (68.6%), and that they preferred tapinarof to prior topicals (88.0%). Compared with systemic drugs used previously for AD, most strongly agreed or agreed that tapinarof was more effective (84.6%), easier to use (77.6%), and that they preferred tapinarof to prior systemic drugs (85.9%). Conclusion: Patient or parent/caregiver satisfaction data from ADORING 3 showed a consistent and highly positive perception of long-term use of tapinarof cream across all parameters, including satisfaction with tapinarof efficacy, cosmetic elegance, application ease, impact on daily life, and preference for tapinarof compared with prior AD therapies. Satisfaction with tapinarof is likely to contribute to long-term adherence and improved outcomes for patients with AD.

Persistent Inadequate Disease Control and Therapeutic Inertia in Moderate-to-Severe Atopic Dermatitis: A 12-month Longitudinal Analysis of Real-world Outcomes from the TARGET-DERM AD registry

Background: Therapeutic inertia refers to the delay or failure in treatment escalation in patients not achieving adequate disease control; it is a challenge in the management of moderate-to-severe atopic dermatitis (AD). Despite the availability of conventional (CST) and advanced systemic therapies (AST) utilized for the treatment of moderate to severe AD, many patients do not achieve treatment success. However, the extent of this inadequacy in real-world clinical practice remains underexplored. Objectives: This study evaluates the occurrence of therapeutic inertia and the proportion of patients with moderate-to-severe AD who continue to show inadequate response after receiving systemic therapies for a duration from 3 to 12 months Methods: We conducted a longitudinal analysis of patients with moderate-to-severe AD (vIGA-AD≥3) from the TARGET-DERM AD registry, including 3,457 participants from 39 centers in the U.S. and Canada. Eligible patients had documented outcomes at the initiation of systemic therapy and after 3 months up to 12 months of follow up. We assessed clinician- and patient-reported outcomes to identify the proportion of patients not meeting treatment targets based on expert consensus. An inadequate response was defined as not achieving a validated Investigator Global Assessment (vIGA-AD) score ≤2, a 50% improvement in Body Surface Area (BSA), and a ≥4-point reduction in the Worst Pruritus Numeric Rating Scale (WP-NRS). An optimal response was defined as a vIGA-AD score ≤1 (clear or almost clear skin), BSA ≤2%, and WP-NRS itch score of 0/1 (complete or almost complete skin resolution). Results: Out of 2,107 patients with moderate-to-severe AD, 445 met the inclusion criteria. The majority were adults (63.8%), female (62.0%), and Non-Hispanic White (45.4%), with an average age of 31 years. Most patients (88.8%) initiated treatment with AST, with dupilumab being the most common (86.5%). The mean vIGA-AD was 3.3 for AST and 3.6 for CST at initiation (P<0.01). At 6 months, 37% and 67% of AST-treated patients had inadequate responses in terms of skin clearance and itch outcomes, respectively, while 82% and 79% did not achieve optimal responses. At 12 months, these figures were approximately 30% and 66% for inadequate responses and 85% and 88% for not achieving optimal responses, respectively. CST-treated patients showed a similar trend. Conclusions: The study reveals that a significant portion of moderate-to-severe AD patients fail to achieve adequate disease control with systemic therapies over 12 months, indicating substantial presence of therapeutic inertia. These findings suggest a need for more proactive management strategies in AD treatment.

Efficacy and Safety of Ruxolitinib Cream by Anatomic Region in Children Aged 2 to 11 Years With Atopic Dermatitis: Results From TRuE-AD3

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease. Ruxolitinib (Janus kinase [JAK]1/JAK2 inhibitor) cream has demonstrated efficacy and safety in patients aged ≥2 years with AD. In adolescents (aged ≥12 y) and adults with AD, application of ruxolitinib cream resulted in significant improvements across all anatomic regions vs vehicle. The objective of this analysis was to evaluate the efficacy and safety of ruxolitinib cream by anatomic region in the randomized, double-blind, phase 3 TRuE-AD3 study (NCT04921969). Children aged 2–11 years with AD for ≥3 months and an Investigator’s Global Assessment score of 2/3 were randomized 2:2:1 to apply 0.75% or 1.5% ruxolitinib cream twice daily (BID) or vehicle BID for 8 weeks. Efficacy was evaluated using the Eczema Area and Severity Index (EASI) subscores for head/neck, trunk, upper limbs, and lower limbs. Of 330 patients in TRuE-AD3, the mean (SD) age was 6.5 (2.9) years, and 179 patients (54.2%) were female; the mean (SD) EASI score was 8.6 (5.4). Improvements in EASI score were demonstrated with 0.75% and 1.5% ruxolitinib cream vs vehicle at first observation (Week 2), with statistically significant differences (at 0.05 alpha level and all P values below are nominal) at Week 8 in the head and neck (−0.63 [P=0.0108] and −0.70 [P=0.0011] vs −0.41), trunk (−0.98 [P=0.0310] and −1.18 [P=0.0003] vs −0.70), upper limbs (−1.81 [P<0.0001] and −2.06 [P<0.0001] vs −1.18), and lower limbs (−2.91 [P<0.0001] and −3.23 [P<0.0001] vs −1.43). Improvements in induration/papulation/edema, erythema, excoriation, and lichenification were observed for both strengths of ruxolitinib cream vs vehicle in all regions at Week 2, with statistical significance (at 0.05 alpha level) in nearly all AD signs and regions at Week 8. Ruxolitinib cream was well tolerated in both treatment groups (n=264), with 4.5% of patients experiencing application site reactions, which was similar to the frequency of application site reactions (4.3%) among patients with head/neck involvement (n=161) . In conclusion, ruxolitinib cream demonstrated significant improvements in AD vs vehicle in children with AD across anatomic regions, including on the head/neck, and was well tolerated. (Funding, Incyte Corporation)

Impact of Therapeutic Inertia on Patient-Reported Outcomes in Moderate-to-Severe Atopic Dermatitis: A 12-Month Longitudinal Study from the TARGET-DERM AD Registry

Background: Therapeutic inertia, the delay or reluctance to modify treatment when goals are unmet, is a significant challenge in managing chronic diseases, including atopic dermatitis (AD). This inertia can lead to suboptimal disease control and affect patient outcomes. Objectives: This study evaluates the effect of therapeutic inertia on patient-reported outcomes (PROs) in moderate-to-severe AD patients undergoing systemic treatment over 3 to 12 months. Methods: We analyzed longitudinal data from the TARGET-DERM AD registry, which includes 3,457 patients with moderate-to-severe AD from 39 centers across the U.S. and Canada. Eligible patients had documented patient-reported outcomes (PROs) at the initiation of systemic therapy and at subsequent 3-month intervals up to 12 months of follow-up. We assessed the proportion of patients not meeting treatment targets based on expert consensus. Patients had a validated Investigator Global Assessment (vIGA-AD) score of 3 or more at initiation of either an advanced systemic therapy (AST) such as biologics or JAK inhibitors or a conventional systemic therapy (CST) such as cyclosporine, methotrexate, or prednisone. PROs were evaluated at 3-month intervals up to 12 months, assessing achievement against the predefined treatment targets. PRO measures included Worst-Itch (PROMIS Itch-Severity), POEM, PO-SCORAD, NRS-sleep, and NRS-pain with specific moderate and optimal target levels established for each. Itch-Severity (range: 0–10; moderate target: ≥4-point reduction, optimal target: score ≤1), POEM (range: 0-28; moderate target: ≥4-point reduction, optimal target: score ≤2), PO-SCORAD (range: 0-103; moderate target: score ≤24; optimal target: score ≤10), NRS-sleep and NRS-pain (range: 0-10; moderate target: reduction ≥3-points; optimal target: score ≤1). Results: Out of 2107 patients with moderate-to-severe AD, 445 qualifying participants were included (63.8% adult, 62.0% female, 45.4% Non-Hispanic White, mean age of 31 years). Most patients (88.8%) initiated AST, with dupilumab being the most common (86.5%). At 6 months, significant proportions of AST-treated patients failed to reach moderate and optimal targets for itch (67% and 79%, respectively), POEM (46% and 69%), and NRS-sleep (59% and 47%). By 12 months, these figures were similar, with 66% and 88% failing to meet itch targets, 53% and 73% failing to meet POEM targets, and 62% and 45% failing to meet NRS-sleep targets, respectively. A similar pattern was observed for other PROs. CST-treated patients exhibited similar trends. Conclusions: The study highlights the profound impact of therapeutic inertia on the quality of life of patients with moderate-to-severe AD. Despite systemic therapy, a considerable proportion failed to meet treatment targets over a 12-month period, underscoring the need for more proactive and responsive treatment strategies in AD management.

Demographics and Disease Characteristics of Patients with Alopecia Areata with Comorbid Atopic Dermatitis, Vitiligo or Anxiety/Depression: TARGET-DERM AA

Introduction Alopecia areata (AA) is a chronic autoimmune disease. Common AA comorbidities include atopic dermatitis (AD), vitiligo, anxiety and depression (AnxDep). TARGET-DERM AA is an ongoing longitudinal, real-world study of United States and Canadian AA patients. The purpose of this analysis is to assess characteristics among AA patients with and without the above comorbidities. Methods At enrollment (December 2021-June 2024), patients reported outcomes (including comorbidities, Patient Global Impression of Severity-AA, and clinician-reported outcome measures: Severity of Alopecia Tool, Measure for Eyebrow/Eyelash Hair Loss). Characteristics were compared across subgroups. Results Of the 267 AA patients with completed patient questionnaires at enrollment, 61.4% were female; 24.4% were aged <12 years, 13.7% 12-17, and 61.7% 18 or older. Overall, 21.0% self-reported an AD diagnosis (19.7% of pediatric, 11.1% of adolescent, and 25.4% of adult AA patients), 7.1% vitiligo (7.0% of pediatric, 3.7% of adolescent, and 8.5% of adult AA patients) and 44.9% AnxDep (21.1% of pediatric, 40.7% of adolescent, and 58.5% of adult AA patients). 42.1% of patients with comorbid vitiligo had severe AA disease (SALT>50) and 27.8% patients without comorbid vitiligo had SALT>50. 28.6% of those with comorbid AD had SALT>50 compared to 28.9% of those not reporting AD, with 30.0% of AnxDep and 27.9% of non-AnxDep having SALT>50, all p>0.2. 42.1% of patients with comorbid vitiligo reported PGIS-AA ‘severe/very severe’ disease, with 41.1% of patients with comorbid AD and 42.5% of patients with comorbid AnxDep reporting severe/very severe AA disease, all numerically higher than patients without comorbid vitiligo (36.3%), AD (35.6%), and AnxDep (31.9%), all p>.07. Among those with and without vitiligo, 42.1% vs 37.9% had eyebrow involvement, 36.8% vs 30.2% eyelash; considering AD, 35.7% vs 38.9% had eyebrow involvement, 28.6% vs 31.3% eyelash; for AnxDep 39.2% vs 37.4% had eyebrow involvement, 30.8% v 30.6% eyelash, all p>0.5. Discussion In this real-world cohort of AA patients, the presence of specific comorbidities was not associated with statistically significant differences in clinician reported AA severity, eyebrow or eyelash involvement. Comorbid AnxDep was associated with increased patient-reported AA disease severity. Additional research characterizing how dermatologic and psychiatric comorbidities impact health-related quality of life and patient burden has the potential to inform management decisions.

Association of Ruxolitinib Cream Initiation With Continued Reduction in Use of Other Topical Treatments, Oral Corticosteroids, and Biologics for Atopic Dermatitis

The objective of this analysis was to examine the impact of ruxolitinib cream on the use of other treatments for atopic dermatitis (AD). This study used claims data from the Healthcare Integrated Research Database (HIRD®) to identify new users of ruxolitinib cream from October 1, 2021, to March 31, 2022. The index date was the date of the first claim for ruxolitinib cream. The baseline period was the 6-month period before the index date, and the follow-up period was 12 months after the index date, which was divided into months 1–6 and months 7–12. Use of other topical and systemic therapies for AD were descriptively analyzed. Among 556 ruxolitinib cream users with follow-up data, the mean number of ruxolitinib cream fills in the overall 12-month follow-up period was 2.1 (SD, 1.77; range, 1–12). The mean (SD) patient age was 40.3 (17.32) years. In months 1–6 and 7–12, 39.9% and 37.4% of patients were treated with ruxolitinib cream monotherapy, respectively; 72.5% and 73.9% of patients did not receive a new class of AD treatment during the respective follow-up periods. Topical corticosteroid use in patients was reduced from 53.4% at baseline to 31.3% in months 1–6 and 26.6% in months 7–12. Topical calcineurin inhibitor use decreased from 14.9% at baseline to 5.2% in months 1–6 and 5.0% in months 7–12. Similarly, topical phosphodiesterase 4 inhibitor use decreased from 6.7% at baseline to 3.4% in months 1–6 and 1.6% in months 7–12. The mean cumulative prednisone-equivalent dose was also reduced from 83.9 mg during the baseline period to 58.0 mg for months 1–6 and 47.3 mg for months 7–12. For patients who did not receive AD biologic therapy during the baseline period (n=431), 92.3% in months 1–6 and 91.4% in months 7–12 continued to remain off AD biologic therapy. Among patients who received AD biologics at baseline (n=125), 16.0% did not receive them in months 1–6 and 26.4% did not receive them in months 7–12. In conclusion, following initiation of ruxolitinib cream, there was a continued reduction in use of other topical therapies and oral corticosteroids for AD. Most biologic-naive patients (>90%) avoided biologics in the 12 months following ruxolitinib cream initiation. Approximately 1 in 4 patients who had biologic treatment during baseline did not continue biologic use in months 7–12. This 12-month analysis confirms earlier 6-month findings that indicated treatment with ruxolitinib cream may reduce the use of other topical therapies, oral corticosteroids, and biologics in patients with AD. (Funding, Incyte Corporation)

Half-life-extended Monoclonal Antibody APG777 for Atopic Dermatitis: Design of the Phase 2 APEX Study

Introduction: Current treatments for moderate-to-severe atopic dermatitis (AD) include topical and systemic therapies. The latter includes monoclonal antibodies (mAbs) targeting the IL-13 pathway, which is implicated in AD pathophysiology. While currently available mAbs directed against the IL-13 pathway have demonstrated efficacy for AD, they require ongoing injections every 2 or 4 weeks. APG777 is a humanized, anti-IL-13 mAb that binds IL-13 and blocks downstream signaling mediated by the IL-13Rα1/IL-4Rα complex. APG777 contains amino acid modifications designed to extend plasma half-life through increased FcRn-mediated antibody recycling. Interim results from an ongoing phase 1 study in healthy participants suggest a favorable safety and PK/PD profile for APG777, and a half-life of approximately 75 days. Methods: APEX (NCT06395948) is a 2-part, multicenter, phase 2, randomized, double-blinded, placebo-controlled clinical trial evaluating the efficacy and safety of APG777 in adults with moderate-to-severe AD. Adults (≥18 years of age) are eligible to participate if they have a diagnosis of AD for ≥1 year prior to screening and exhibit moderate-to-severe AD (EASI ≥16, IGA ≥3, BSA ≥10%) at both screening and baseline visits. Part A of the study (proof-of-concept) is evaluating the efficacy and safety of one induction dose regimen of APG777 compared with placebo over 16 weeks; this is followed by a 36-week maintenance period. Part B (dose-regimen finding) will evaluate different dose regimens of APG777 compared with placebo over 16 weeks followed by a 36-week maintenance period. Participants completing the maintenance period of Part A or B of the study will be eligible to enroll in a separate long-term extension study or enter the post-treatment follow-up period (up to 52 weeks). The primary outcome measure for the study is the percentage change from baseline to week 16 in the Eczema Area and Severity Index (EASI). The APEX study is currently enrolling.

Real-World Effectiveness of Upadacitinib in Moderate‑to‑Severe Atopic Dermatitis (AD): Results From Longitudinal Analyses of the CorEvitas AD Registry

Introduction: Clinical trials demonstrated that upadacitinib is efficacious in treating atopic dermatitis (AD). Its real-world effectiveness is less understood. In this study, we investigated the longitudinal real-world outcomes of upadacitinib-treated adults in the CorEvitas AD Registry. Methods: The CorEvitas AD Registry is a prospective, non-interventional registry of adults diagnosed with AD in the United States and Canada. We evaluated participants enrolled through April 30, 2024 with data available prior to upadacitinib exposure (baseline) and at the six-month follow-up visit, and were receiving upadacitinib at the follow-up visit. Outcomes evaluated include the achievement of: Validated Investigators Global Assessment Scale for Atopic Dermatitis (vIGA-ADTM) of “clear” or “almost clear” among participants rated “mild” or worse at baseline (vIGA-AD 0/1); Eczema Area and Severity Index improvement of ≥75%/≥90%/100% from baseline (EASI 75/90/100); Peak Pruritus Numeric Rating Scale (PP-NRS) improvement ≥4 among participants with a score ≥4 at baseline (∆PP-NRS≥4); PP-NRS score of 0 or 1 among participants with a score >1 at baseline (PP-NRS 0/1); Dermatology Life Quality Index (DLQI) score improvement ≥4 among participants with a score ≥4 at baseline (∆DLQI≥4); and DLQI score of 0 or 1 among participants with a score >1 at baseline (DLQI 0/1). Simultaneous achievement of both EASI 90 & PP-NRS 0/1 was also assessed. Data were analyzed as observed with no imputation. Safety events were not assessed in this analysis. Results: The longitudinal analysis included 192 participants (mean age 46.2 years; 57.8% female; 69.8% White; 43.8% prior exposure to dupilumab or tralokinumab; 64.4% receiving 15 mg dose at follow-up visit; mean upadacitinib treatment duration of 6.0 months). More than half achieved clear/almost clear skin (66.1% vIGA-AD 0/1), EASI 75 (69.3%), and EASI 90 (59.2%); 45.3% achieved complete skin clearance (EASI 100). More than 40% reported little-to-no itch (44.4% PP-NRS 0/1) and no impact of AD on quality of life (43.3% DLQI 0/1), and more than half reported meaningful improvements in itch (58.6% ∆PP-NRS≥4) and quality of life (76.0% ∆DLQI≥4). Simultaneous attainment of both EASI 90 & PP-NRS 0/1 was achieved in 46.6% of participants at 6 months. Conclusions: In the real-world setting, the majority of adults treated and remained on upadacitinib achieved clinically meaningful outcomes in skin lesions, itch, and quality of life, with many achieving complete skin clearance, little-to-no itch, and experiencing no impact of AD on their quality of life. These findings underscore upadacitinib's potential to offer multidimensional relief to patients with AD in everyday clinical practice.

Why Do Optimal Targets for Itch and Skin Clearance Matter in Atopic Dermatitis Treatment? Insights from TARGET-DERM AD Registry

Introduction/Background: Atopic dermatitis (AD) patients undergoing treatment may only experience partial improvement in itch and skin lesions, often leading to suboptimal outcomes. The Aiming High in Eczema/Atopic Dermatitis (AHEAD) treat-to-target recommendations emphasize the importance of achieving optimal treatment targets, such as complete or near-complete itch relief and skin clearance. However, there is limited evidence on the impact of achieving these higher efficacy targets on patient-reported outcomes and quality of life in AD. Objectives: To evaluate the independent and combined effects of achieving optimal treatment targets for itch and skin clearance on patient-reported outcomes (PROs) in AD, based on the AHEAD treat-to-target recommendations. Method: A cross-sectional analysis was conducted on adult participants in TARGET-DERM AD, a longitudinal study with over 4,000 participants across 52 U.S. and Canadian clinical-practice sites (2019-2024). Itch severity was measured using the PROMIS Itch-Severity question (NRS-Itch, 0–10 scale), with scores of 0/1 indicating no or minimal itch. Skin severity was assessed using the validated Investigator Global Assessment (vIGA-AD), where 0/1 represents clear or almost clear skin. Associations between itch and skin severity with optimal patient outcomes including POEM 0–2 (clear/almost-clear disease), DLQI 0/1 (minimal/no impact on quality of life), NRS-Sleep 0/1, and NRS-Pain 0/1 were evaluated. Logistic regression models examined the main and interaction effects of itch and skin severity. Results: Among 1,920 patients (58.6% female; 54.5% Non-Hispanic White; 93.8% US; mean age 45 years), optimal DLQI, POEM, NRS-Sleep, and NRS-Pain occurred most frequently among those achieving the optimal treatment targets for itch (WI-NRS 0/1; 52.1%, 53.7%, 57.3%, and 83.1%, respectively) and skin clearance (vIGA-AD 0/1; 44.7%, 44.3%, 44.7%, and 74.3%, respectively). Compared to partial improvement, the adjusted odds ratios (aOR) of optimal PROs were greatest for participants with complete or near-complete resolution of both itch and skin lesions (DLQI 0/1: 20.0; POEM 0-2: 41.7; Sleep-NRS: 16.1; Pain-NRS: 6.0). Conclusions: Achieving optimal treatment targets for both itch and skin lesions markedly enhances patient-reported outcomes in AD. The results of this real-world study support treat-to-optimal targets to assess therapeutic effectiveness and optimize patient outcomes.

Long-Term Maintenance of Optimal Treatment Targets for Skin and Itch Outcomes With Upadacitinib in Moderate-to-Severe Atopic Dermatitis: 140-Week Results From the Phase 3 Measure Up 1 and 2 Studies

Introduction: Despite undergoing prolonged systemic therapy, many patients with moderate-to-severe atopic dermatitis (AD) do not achieve optimal targets for skin and itch outcomes as defined by Aiming High in Eczema/AD (AHEAD) recommendations (eg, ≥90% improvement from baseline in Eczema Area and Severity Index [EASI 90] and Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1 [no/minimal itch]). We evaluated long-term maintenance of optimal treatment targets with upadacitinib, an oral selective JAK inhibitor approved for moderate-to-severe AD in adolescents and adults. Methods: This 140-week interim analysis included adolescents and adults with moderate-to-severe AD who were randomized at baseline to upadacitinib 15 mg (UPA15) or 30 mg (UPA30) in the ongoing, phase 3, double-blind Measure Up 1 and 2 studies. Assessments included the proportion of patients (at the population level) who maintained EASI 90, WP-NRS 0/1, or simultaneous achievement of EASI 90 + WP-NRS 0/1 responses from week 16 (end of the placebo-controlled period) onwards. Data are reported as observed cases with no imputation for missing data. Results: Among patients who achieved EASI 90 at week 16 (UPA15, n=298; UPA30, n=384), EASI 90 was maintained by 79.8% (UPA15) and 83.7% (UPA30) at week 52, 76.7% (UPA15) and 83.0% (UPA30) at week 100, and 74.0% (UPA15) and 84.2% (UPA30) at week 140. Of patients achieving WP-NRS 0/1 at week 16 (UPA15, n=193; UPA30, n=281), WP-NRS 0/1 was maintained by 69.4% (UPA15) and 72.0% (UPA30) at week 52, 65.6% (UPA15) and 68.4% (UPA30) at week 100, and 62.3% (UPA15) and 66.0% (UPA30) at week 140. Of patients simultaneously achieving EASI 90 + WP-NRS 0/1 at week 16 (UPA15, n=156; UPA30, n=243), maintenance was achieved by 68.1% (UPA15) and 70.8% (UPA30) at week 52, 62.7% (UPA15) and 66.5% (UPA30) at week 100, and 58.7% (UPA15) and 64.4% (UPA30) at week 140. Among patients who did not maintain optimal outcomes, most still achieved clinically meaningful responses. Conclusion: Most patients maintained optimal skin and itch outcomes through 140 weeks of upadacitinib treatment, demonstrating its potential to provide sustained long-term disease control in atopic dermatitis.

Switching from Dupilumab to Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis and Inadequate Response to Dupilumab: Efficacy and Safety Results from the Phase 3b/4 LEVEL UP Study

Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Upadacitinib (UPA), a selective oral Janus kinase (JAK) inhibitor, and dupilumab (DUPI), a monoclonal antibody targeting interleukin-4 and interleukin-13 signaling, are both approved treatments for moderate-to-severe AD. LEVEL UP is a phase 3b/4 efficacy assessor blinded monotherapy study comparing UPA to DUPI for treatment of moderate-to-severe AD in adults and adolescents over a 16-week period (Period 1). Patients not achieving ≥75% improvement in the Eczema Area and Severity Index (EASI 75) from baseline at Week 16 entered an additional 16-week extension phase (Period 2). In Period 2, patients either continued/escalated to UPA 30 mg (UPA/UPA 30) or switched from DUPI to UPA 15 mg (DUPI/UPA), with the potential to escalate to 30 mg based on clinical response. Efficacy for skin and itch outcomes in Period 2 were assessed using observed case analysis while on treatment, without statistical comparisons. Here we report efficacy and safety results for the DUPI/UPA switch group. A total of 355 patients who did not achieve EASI 75 at Week 16 entered Period 2 of the study (DUPI/UPA, N=208). At Week 32, response rates in the DUPI/UPA group were: 79.6%, 58.7%, and 19.9% achieving EASI 75, EASI 90, and EASI 100, respectively; 60.2% achieving WP-NRS improvement ≥4 among those with baseline WP-NRS ≥4; 37.0% achieving WP-NRS 0/1 among those with baseline WP-NRS >1; and 26.8% simultaneously achieving EASI 90 and WP-NRS 0/1 by Week 32. Clinically meaningful outcomes were also observed at an earlier visit (Week 20). No new safety signals through Week 32 were identified compared to the established safety profile of UPA. Most patients with an inadequate response to DUPI at Week 16 experienced clinically meaningful improvements in skin clearance and itch at 4 weeks post-switch to UPA, with additional patients achieving these outcomes by 16 weeks post-switch. These findings suggest that switching from DUPI to UPA is an effective treatment strategy for patients who do not meet moderate or optimal treatment targets with DUPI.

Achievement of No-to-minimal Itch and Sleep Improvement with Tapinarof Cream 1% Once Daily in Two Pivotal Phase 3 Trials in Adults and Children Down to 2 Years of Age with Atopic Dermatitis

Introduction: Itch frequently causes sleep disturbance in patients with atopic dermatitis (AD). The gold-standard Peak Pruritus Numerical Rating Scale (PP-NRS) improvement from baseline is 4 points; however, more stringent outcomes include achieving no-to-minimal itch (PP-NRS ≤1). Tapinarof cream 1% once daily (QD) demonstrated superior efficacy, including itch reduction, versus vehicle and was well tolerated in adults and children down to 2 years of age with AD in the ADORING 1 and 2 pivotal phase 3 trials. Here we present highly stringent itch outcomes and sleep improvement with tapinarof from these trials. Methods: In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic Dermatitis™ score ≥3 (moderate or severe), Eczema Area and Severity Index score ≥6, and body surface area involvement of 5–35% were randomized to tapinarof cream or vehicle QD for 8 weeks. Stringent PP-NRS assessments were analyzed post hoc and included achieving no‑to‑minimal itch (PP-NRS ≤1) or PP-NRS score <2. Mean weekly PP-NRS scores were assessed on an 11-point scale (0 indicates “no itch” and 10 is “worst imaginable itch”). The Patient Oriented Eczema Measure (POEM) question 2 evaluated sleep disturbance on a 5-point scale (0 indicates “no days” and 4 is “every day”); outcomes were pooled and stratified by age. Results: 407 and 406 patients were randomized in ADORING 1 and 2. Mean baseline scores were similar across ADORING 1 and 2 treatment groups: PP-NRS, 6.7 and 6.8; pooled POEM sleep disturbance scores, 2.0 (aged ≥12 years) and 2.4 (<12 years), respectively. Statistically significant achievement of no-to-minimal itch (PP-NRS ≤1), PP-NRS <2, and improvement in sleep were achieved with tapinarof versus vehicle as early as Week 1, the first assessment, and continued through Week 8. Stringent itch outcomes were achieved with tapinarof versus vehicle at Week 8: no-to-minimal itch, 31.4% versus 17.4% (P=0.0072) and 33.0% versus 14.0% (P=0.0003); and PP-NRS <2, 48.1% versus 28.4% (P=0.0006) and 46.8% versus 19.6% (P<0.0001) in ADORING 1 and 2, respectively. Sleep scores improved with tapinarof versus vehicle at Week 8: –1.4 versus –0.8 (≥12 years); –1.7 versus –1.0 (<12 years; both P<0.0001). Conclusion: Tapinarof cream 1% QD demonstrated early, significant, and meaningful achievement of no-to-minimal itch and improvement of sleep in adults and children down to 2 years of age with AD.

Skin Clearance, Treatment Response Off-therapy, and Safety of Tapinarof Cream 1% Once Daily: Results from ADORING 3, a 48-week Phase 3 Trial in Adults and Children Down to 2 Years of Age with Atopic Dermatitis

Introduction: In the ADORING 1 and 2 phase 3 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) demonstrated significant efficacy and was well tolerated in patients down to age 2 years with atopic dermatitis (AD). We present efficacy, safety, and tolerability outcomes from ADORING 3. Methods: Eligible patients from ADORING 1, ADORING 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild, or moderate or severe AD, that did not meet eligibility criteria for ADORING 1 or 2, received tapinarof cream 1% QD for up to 48 weeks. Efficacy endpoints included achievement of complete disease clearance (Validated Investigator Global Assessment for Atopic Dermatitis™ [vIGA-AD™] score=0 [clear]), and clear or almost clear skin (vIGA-AD™=0 or 1). Safety and tolerability were assessed. Patients entering with vIGA-AD™≥1 were treated with tapinarof until complete clearance (vIGA-AD™=0 [clear]). Those entering with or achieving complete clearance discontinued tapinarof and were assessed for maintenance of clear or almost clear skin off-treatment (duration of treatment-free interval). Patients whose AD returned to mild (vIGA-AD™≥2) were re-treated until complete clearance was achieved. Results: 728 patients enrolled; 83.0% were pediatric (2–17 years). Overall, 51.9% (378/728) achieved complete disease clearance, and 81.6% achieved clear or almost clear skin at least once in the trial. Mean duration of first treatment-free interval was 79.8 consecutive days (standard deviation: 81.4 days). No tachyphylaxis on either continuous or intermittent therapy was observed for up to 48 weeks. Most frequent adverse events were folliculitis (12.1%), nasopharyngitis (6.9%), and upper respiratory tract infection (6.9%). Follicular events and contact dermatitis were mostly mild or moderate and associated with low discontinuations (1.0% and 0.4%, respectively). Tapinarof was well tolerated locally, even when applied on sensitive skin. Conclusions: Tapinarof cream monotherapy demonstrated a high rate of complete disease clearance in patients down to age 2 years with AD. After discontinuing tapinarof, patients maintained clear or almost clear skin for 79.8 consecutive days. Tapinarof was well tolerated over 48 weeks.

Targeted 308-nm Excimer Laser A Safe and Effective Solution for Inflammatory Skin Disorders

Background: The 308-nanometer excimer laser is a targeted ultraviolet B (UVB) light therapy that delivers high-intensity UVB rays directly to affected skin. It has shown considerable efficacy in managing various inflammatory skin conditions, including Psoriasis, Vitiligo, Atopic dermatitis (Eczema), Leukoderma, Alopecia Areata, Chronic recalcitrant dermatitis, Lichen planus, Cutaneous T-cell Lymphoma (e.g. Mycosis fungoides/ Sezary Syndrome), Parapsoriasis, Pityriasis lichenoides chronica, Pruritus, Urticaria pigmentosa, Superficial mycoses (e.g., dermatophytosis [ringworm]. The patient demographic of some of these conditions (e.g. Vitiligo) tends to skew towards patients with darker skin tones. Results: The excimer laser is particularly effective for treating resistant areas, such as the scalp, palmoplantar psoriasis, and hand and foot dermatitis, which often do not respond well to conventional therapies. It has also demonstrated notable success in promoting repigmentation in facial vitiligo, especially in patients with Fitzpatrick skin types IV–VI. Treatment results are typically observed quickly after 5-10 sessions, with sustained improvement and psoriasis clearance evident even at 1-year follow-up. Over the years, access to the Excimer laser procedures has expanded with the availability of these procedures in many private clinics as well as academic facilities. That has increased the availability of the treatment modality and patient choice of therapy. Conclusions: The excimer laser provides a safe, non-invasive treatment option with a strong record of efficacy for multiple inflammatory skin conditions. It is a viable alternative to systemic therapies and can be used either alone or in conjunction with other treatments for optimal patient outcomes.

Dupilumab Demonstrates a Higher Likelihood of Achieving Improvements in Signs, Symptoms, and Quality of Life vs. Tralokinumab at Week 16: Results from a Bucher Indirect Treatment Comparison

Background: Dupilumab and tralokinumab are biologics approved by the US Food and Drug Administration (FDA) for the treatment of patients with moderate-to-severe atopic dermatitis (AD), aged ≥6 months and ≥12 years, respectively. Dupilumab and tralokinumab have demonstrated efficacy and safety in clinical trials. However, no direct head-to-head trials have been performed to compare the efficacy of dupilumab vs tralokinumab. The Bucher indirect treatment comparison (ITC) is a robust, placebo-adjusted, and accepted method to evaluate the relative efficacy of drugs in the absence of direct comparisons. The objective of this analysis was to report results from a Bucher ITC comparing the efficacy of dupilumab+topical corticosteroid (TCS) vs tralokinumab+TCS at Week 16. Methods: The placebo-adjusted Bucher ITC included published data from the two similarly designed phase 3 trials, LIBERTY AD CHRONOS (NCT02260986) and ECZTRA 3 (NCT03363854). For both studies, data from the 16-week period were used, employing non-responder imputation, with the following doses: 300mg dupilumab every 2 weeks (q2w)+TCS or placebo+TCS, and 300mg tralokinumab q2w+TCS or placebo+TCS. The evaluated endpoints included the proportions of patients achieving an Investigator’s Global Assessment score 0/1 (IGA 0/1; clear/almost clear), 75% and 90% improvements from baseline in Eczema Area and Severity Index (EASI-75 and EASI-90), ≥4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale score (PP-NRS >4), and ≥4-point improvement from baseline in the Dermatology Life Quality Index (DLQI >4). The Bucher ITC with the frequentist approach was performed using R software (v 4.20; netmeta package) with a fixed-effect model. Results were reported as odds ratio (OR) with 95% confidence interval (CI). Results: A total of 801 patients (LIBERTY AD CHRONOS: placebo+TCS: 315; dupilumab+TCS: 106; ECZTRA 3: placebo+TCS: 127; tralokinumab+TCS: 253) were included in the Bucher ITC. Baseline disease characteristics indicated comparable severity between the two trial populations based on IGA and PP-NRS. However, CHRONOS showed slightly higher baseline EASI scores (median [Q1, Q3] score 30.9 [22.3, 41.6] vs. ECZTRA 3: 24.7 [18.4, 35.9]), while ECZTRA 3 showed slightly higher DLQI scores (median [Q1, Q3] score 18.0 [12.0, 23.0] vs. CHRONOS: 13.5 [8.0, 20.0]). Patients treated with dupilumab+TCS had a significantly higher likelihood of achieving IGA 0/1 (OR=2.49, 95%CI 1.24–5.00), EASI-75 (OR=3.21, 95%CI 1.66–6.19), EASI-90 (OR=2.92, 95%CI 1.41–6.02), PP-NRS ≥4 (OR=3.62, 95%CI 1.87–7.00), and DLQI ≥4 (OR=2.16, 95%CI 1.03–4.54) at Week 16 vs those treated with tralokinumab+TCS. Conclusions: A placebo-adjusted Bucher ITC showed that the likelihood of achieving improvements in signs, symptom, and quality of life is significantly higher for patients treated with dupilumab+TCS vs tralokinumab+TCS at Week 16.

Worldwide Clinical and Real-World Exposure to Baricitinib

Introduction: Baricitinib (BARI), an oral selective JAK inhibitor, is approved in many geographies for adults with rheumatoid arthritis or alopecia areata and for patients as young as age 2 years with atopic dermatitis or juvenile idiopathic arthritis. It is also approved in the US for hospitalized patients with COVID-19 infection. We report the worldwide clinical trial and real-world exposure to BARI across a range of diseases, ages and racial backgrounds. Methods: Real-world patient exposure estimates were calculated based on total mg sold, average daily dose, and average length of therapy as reported to regulatory agencies through the cumulative timeframe ending Jan. 31, 2024. Clinical trial exposures were based on actual exposures from completed trials through Feb. 13, 2024, and estimates were made for ongoing blinded trials based on the enrolment/randomization schemes Results: In the real-world setting, an estimated 1,836,600 patients have been exposed to the following BARI doses: 1 mg, ~2,000 (0.1%); 2 mg, ~524,900 (28.6%); 4 mg, ~1,309,600 (71.3%). Of these estimated exposures, ~ 57% were for COVID-19 with the remaining for all other indications combined. Across 59 clinical trials (completed and ongoing), an estimated 14,660 subjects (548 healthy volunteers and 14,112 patients) have received BARI since June 2008. Exposures from completed studies include 10,276 patients (62% female), 399 of whom were <18 yrs of age (≤1 month, N=4; 1 month - ≤2 yrs, N=24; >2 - ≤12 yrs, N=111; >12 - ≤18 yrs, N=260), 8820 were >18 to ≤65 yrs, 1027 were >65 yrs, and 30 had age unknown. An additional 467 adolescent and pediatric patients down to the age of 2 have been treated with BARI for atopic dermatitis in an ongoing clinical trial, bringing the total number of patients <18 years of age to 866 across dermatologic, rheumatologic, other autoimmunologic, and acute infectious diseases (excluding alopecia areata for which there is an ongoing pediatric trial). Clinical trial exposures by racial and ethnic background are as follows: Asian, N=2,491; Black, N=450; Caucasian, N=6,237; other, N=496; multiple, N=135; unknown, N=467. Conclusion: There has been extensive real-world exposure to BARI across indications and populations, and BARI is a well-studied molecule in clinical trials, across varied disease states, racial populations and ages. Since average daily dose and length of therapy may vary over time, real-world exposures are only an estimate of total patients receiving BARI. Exposures in clinical trials include patients as young as less than 1 month of age up to patients over the age of 65 years. While these exposures do not indicate efficacy or safety, they provide data to establish the overall profile of the drug and can inform on its performance over time across a variety of populations.

Omega Fatty Acids and Its Role in Amelioration of Canine Dermatological Disorders

Omega-3 and omega-6 fatty acids (FA) are crucial dietary components for dogs, playing a vital role in maintaining healthy skin. Omega-3 FA possess anti-inflammatory properties, potentially aiding in managing conditions like allergies and atopic dermatitis that cause itching and irritation. Omega-6 FA contribute to healthy skin barrier function, protecting against environmental allergens and pathogens. However, excessive omega-6 intake can promote inflammation. An optimal ratio of omega-3 to omega-6 fatty acids in a dog's diet is essential. Omega-3s are found in fatty fish (salmon, mackerel) and fish oil, while omega-6s are abundant in vegetable oils (sunflower, soybean). If homemade foods are not properly balanced, they may easily be deficient in many essential nutrients. Various skin problems like alopecia, scaly skin, dry, pruritic and skin infections can result from this. Proper dietary management with balanced omega-3 and omega-6 intake can significantly benefit dogs suffering from skin conditions. A well-balanced diet is essential for maintaining the health of the skin.

Optimized Second-Generation IL-4Rα Inhibition: Structural and Molecular Dynamics Properties of Rademikibart Fab-IL-4Rα Complex

Introduction: Global Burden of Disease studies showed atopic dermatitis (AD) and asthma are the top two immune-mediated inflammatory diseases at younger age [1]. Dupilumab was the initial first-generation interleukin-4 receptor alpha (IL-4Rα) inhibitor for treating both type I and type II IL-4Rα-dependent inflammatory disorders. Following recent clinical trials, rademikibart (previously, CBP-201) emerges as an optimized next-generation human monoclonal antibody with higher binding affinity to IL-4Rα compared to dupilumab [2]. It demonstrated better effect in inhibiting STAT6 intracellular signaling in vitro and provided similar potency inhibiting both IL-4 induced TARC release and IL-4 induced B cell activation [2]. Materials & Methods: X-ray crystallography was used to determine the atomic resolution 3D structure of rademikibart fragment antigen binding (Fab) bound to IL-4Rα. This structure was analyzed and compared computationally with the 2.82 Å resolution crystal structure of dupilumab Fab bound to IL-4Rα (Protein Data Bank Code 6WGL). Molecular dynamics studies on rademikibart and dupilumab bound to IL-4Rα examined the stability of the complexes and effects of amino acid mutations on complex formation. Results: The x-ray crystal structure of rademikibart Fab bound to IL-4Rα was determined at 2.71Å and compared to the complex of dupilumab Fab and IL-4Rα. The rotation angle between dupilumab and rademikibart bound to IL- 4Rα is 59.17°. This rotation enables the epitope of rademikibart, but not dupilumab, on IL-4Rα to overlap more closely with the conserved binding interface utilized by IL-4 and IL-13 cytokines. Molecular dynamics simulations of rademikibart Fab and dupilumab Fab complexed with IL-4Rα showed the third interface loop (residues 148 to 152 in domain 2) of IL-4Rα interacts directly with rademikibart, which is absent in dupilumab/IL- 4Rα complex. This finding is confirmed by analysis of the hydrogen bond interactions at the interface between the antibodies and IL-4Rα, demonstrating superior binding energy for rademikibart. Through single amino acid mutation analysis on rademikibart, we identified residue Y50 on rademikibart as the key residue interacting with IL- 4Rα’s third interface loop. Conclusion: Our data provide a molecular and structural rationale for the enhanced IL-4Rα inhibition by rademikibart over dupilumab, confirming rademikibart as an optimized second-generation IL-4Rα inhibitor.

Recalcitrant Scalp Psoriasis Successfully Treated with Once-Daily Roflumilast Cream 0.3%

Scalp psoriasis is a chronic, immune-mediated skin disease with varying phenotypes and is estimated to affect up to 80% of individuals suffering from psoriasis [1]. The physical symptoms, along with social and emotional impacts of scalp psoriasis can significantly reduce quality of life, necessitating long-term treatment for most patients [3]. Numerous topical and systemic treatments are available for scalp psoriasis, yet the condition remains challenging to manage, underscoring a persistent unmet need for safe and effective therapies [2]. Treatment of the scalp and other hair bearing areas is challenging and can affect the ability to apply topical products and hinder their efficacy [2, 3]. Roflumilast cream 0.3% is a highly selective, non-steroidal and potent topical phosphodiesterase 4 (PDE4) inhibitor approved in 2022 by the FDA for the treatment of psoriasis, including intertriginous disease; in 2023 as a foam for the treatment of seborrheic dermatitis and in 2024, roflumilast cream 0.15% was approved for the treatment of atopic dermatitis. Roflumilast has demonstrated a higher affinity for binding to PDE4 relative to other approved PDE4 inhibitors resulting in greater potency [4, 5]. The results of a phase 3 study investigating roflumilast foam 0.3% in patients with scalp and body psoriasis showed that once daily treatment produced significant clearance of affected areas, rapid improvement in pruritus, and was well-tolerated [6]. Here we report a case involving a 28-year-old female with recalcitrant scalp psoriasis following 10 years of unsuccessful treatment with topical products. Due to the severity of adverse effects experienced with prior therapies, the patient was reluctant to initiate systemic therapy and a trial of once daily topical roflumilast cream 0.3% was initiated. The patient demonstrated rapid improvement after 3 days and clearance of the scalp lesion following daily application for 5 days without any reported adverse effects. Lesions on the patient’s torso also cleared. Upon clearance of lesions, the patient discontinued application of roflumilast cream, and lesions remained clear for several weeks and applies only as needed with any recurrence. Our patient’s case demonstrates the significant potential of roflumilast cream 0.3% in addressing the inflammatory etiology of scalp psoriasis.

Efficacy and Safety of Ruxolitinib Cream for the Treatment of Moderate to Severe Chronic Hand Eczema: Top-Line Results From a 16-Week, Multicenter, Randomized, Double-Blind Study

Hand eczema is a common inflammatory disorder involving skin of the hands. Chronic hand eczema (CHE) is defined as hand eczema that persists for >3 months or recurs ≥2 times within a 12-month period. The efficacy and safety of ruxolitinib (selective Janus kinase [JAK] 1/JAK2 inhibitor) cream was investigated in adults with moderate to severe CHE in a phase 2, randomized, double-blind, vehicle-controlled study (NCT05906628). Patients aged ≥18 years with a diagnosis of CHE for ≥6 months, an Investigator’s Global Assessment (IGA)-CHE score of 3 or 4, and no current or history (≤5 y) of atopic dermatitis were randomized 1:1 to apply twice-daily 1.5% ruxolitinib cream or vehicle cream for 16 weeks of double-blind treatment. Patients (N=186) had a median (range) age of 50.0 (18–80) years, and 59.7% were female. The median (range) Itch numerical rating scale (NRS) score was 6.6 (2.1–10), and 72.6% of patients had an IGA-CHE score of 3. At Week 16, significantly more patients who applied ruxolitinib cream versus vehicle achieved IGA-CHE treatment success (primary endpoint; 53.2% vs 10.9%; P<0.0001), defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement from baseline. Significantly more patients who applied ruxolitinib cream versus vehicle achieved a ≥4-point improvement from baseline in Itch NRS score (Itch NRS4) at Week 4 (46.7% vs 17.6%; P<0.0001; key secondary endpoint) and Week 16 (52.2% vs 23.1%; P<0.0001; key secondary endpoint). Numerical improvements in Itch NRS4 with ruxolitinib cream versus vehicle were observed at Day 2 with statistically significant improvement observed on Day 7 (27.4% vs 9.0%; P=0.0024; key secondary endpoint). Substantially more patients who applied ruxolitinib cream versus vehicle achieved a ≥75% or ≥90% improvement from baseline in Hand Eczema Severity Index (HECSI) score at Week 16 (80.2% vs 26.9% and 64.0% vs 11.5%, respectively). Ruxolitinib cream was generally well tolerated through Week 16 with no new safety signals; no serious infections, major adverse cardiovascular events, malignancies, or thromboses were observed. Application site reactions were infrequent. No treatment-related grade ≥3 treatment-emergent adverse events (TEAEs) were reported, and no patients discontinued owing to a TEAE. In conclusion, ruxolitinib cream demonstrated significant reductions of CHE signs and symptoms versus vehicle through Week 16 and was generally well tolerated, consistent with the known safety profile. (Funding, Incyte Corporation)