Eczema Area And Severity Index Research Articles

Efficacy and Safety of Crisaborole Ointment 2% in Chinese Patients Aged ≥ 2 Years with Mild to Moderate Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic immuno-inflammatory skin disease. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild to moderate AD. This post hoc analysis assesses the efficacy and safety of crisaborole in Chinese patients aged ≥ 2years with mild to moderate AD. We evaluated the efficacy and safety of crisaborole in Chinese patients from the vehicle-controlled, phase 3 CrisADe CLEAR study. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily, respectively, for 28days. The primary endpoint was percent change from baseline in Eczema Area and Severity Index (EASI) total score at day 29. Key secondary endpoints were improvement in Investigator's Static Global Assessment (ISGA), ISGA success, and change from baseline in weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score. Adverse events were documented. Of 391 patients in the overall study, 237 were from China, 157 assigned to crisaborole and 80 assigned to vehicle. A greater reduction in percent change from baseline in EASI total score at day 29 was shown in the crisaborole vs. vehicle group (least squares mean [LSM]: -66.34 [95% (confidence interval) CI -71.55 to -61.12] vs. -50.18 [95% CI -58.02 to -42.34]). Response rates for achievement of ISGA improvement (43.2% [95% CI 35.4-51.1] vs. 33.4% [95% CI 22.5-44.2]) and ISGA success (31.7% [95% CI 24.3-39.0] vs. 21.5% [95% CI 12.1-30.9]) at day 29 were higher in the crisaborole vs. vehicle group. A greater reduction in change from baseline in weekly average PP-NRS score at week 4 was observed in the crisaborole vs. vehicle group (LSM: -1.98 [95% CI -2.34 to -1.62] vs. -1.08 [95% CI -1.63 to -0.53]). No new safety signals were observed. Crisaborole was effective and well tolerated in Chinese patients aged ≥ 2years with mild to moderate AD. ClinicalTrials.gov, NCT04360187.

Real-World Clinical, Psychosocial, and Economic Burden of Atopic Dermatitis: Results From the ESSENTIAL AD Multicountry Study.

Limited real-world evidence exists about the burden of atopic dermatitis (AD) in patients receiving systemic or non-systemic therapies in clinical practices. ESSENTIAL AD was an observational study that aimed to fill this information gap. ESSENTIAL AD enrolled (September 2021-June 2022) adult patients with physician-confirmed AD that was routinely managed with systemic and non-systemic treatment in a real-world setting from 15 countries in Eastern Europe, the Middle East, and Africa. Primary outcome variables were Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), and Dermatology Life Quality Index (DLQI) assessed during one office visit. A total of 799 enrolled patients fulfilled selection criteria and were included in the study. Patients mean (standard deviation [SD]) age was 36.3 (14.4) years, 457 (57.2%) were female, and the majority of patients were white (647 [81.0%]). Mean (SD) time since AD diagnosis was 17.6 (15.2) years (median 16.5; interquartile range [IQR] 3.3-26.8). The mean (SD) EASI, SCORAD, and DLQI total scores were 11.3 (11.3 [median 8.1; IQR 3.6-15.8]), 37.8 (17.9 [median 35.5; IQR 24.2-49.0]), and 10.6 (7.2 [median 10.0; IQR 5.0-15.0]), respectively. Patients receiving systemic treatment had significantly higher disease burden (mean [SD] EASI 13.3 [13.0]; median [IQR] 9.6 [3.9-17.9]) versus non-systemic treatment (mean [SD] 9.3 [8.7]; median [IQR] 6.8 [3.0-13.2]; P < 0.0001). Results were similar for SCORAD (39.9 [19.6] vs 35.6 [15.7]; median [IQR] 38.6 [24.7-53.1] vs 32.6 [23.9-44.6]; P = 0.0017), and DLQI total scores (11.4 [7.4] vs 9.9 [6.9]; median [IQR] 11.0 [5.0-16.0] vs 9.0 [5.0-14.0]; P = 0.0033, respectively). Patients with AD continue to have substantial disease burden despite treatment with systemic therapy, suggesting that a need for effective disease management remains, including effective therapies that improve psychological outcomes and reduce economic burden of AD, in Eastern Europe, the Middle East, and Africa.

Lebrikizumab Provides Rapid Clinical Responses Across All Eczema Area and Severity Index Body Regions and Clinical Signs in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis.

Atopic dermatitis (AD) affects multiple areas of the body, some of which may be more refractory to treatment. We evaluated improvements in the Eczema Area and Severity Index (EASI) by body region and clinical signs for each body region in lebrikizumab-treated patients with moderate-to-severe AD. ADvocate 1 and ADvocate 2 compared lebrikizumab 250mg as monotherapy every 2weeks versus placebo for 16weeks. Efficacy measures included EASI, which rates the extent and severity of four clinical signs (erythema, edema/papulation, excoriation, lichenification) in four body regions (head/neck, upper extremities, trunk, lower extremities). Analyses are post hoc. Mean baseline EASI, body region EASI subscores, and the severity of clinical signs were consistent across both studies (EASI ranging from 16.0 to 72.0). At week 16 in both studies, patients treated with lebrikizumab showed significantly greater percent improvement in EASI across all body regions versus placebo (p ≤ 0.001), with improvements as early as week 2. In ADvocate 1, all clinical signs significantly improved across all body regions at week 16 with lebrikizumab (51.4-71.6% improvement) versus placebo (23.1-43.5%, p ≤ 0.001), with significant improvements as early as week 2 for all signs. Significant improvements for all clinical signs at week 16 were also seen in ADvocate 2 for lebrikizumab (53.5-75.6%) versus placebo (28.5-41.2%, p ≤ 0.001) and as early as week 2 for all body regions and signs except head/neck erythema and lower extremity erythema, edema/papulation, and lichenification, which showed significant improvement by week 4. Lebrikizumab as monotherapy consistently and rapidly reduced the extent of involvement and severity of AD in all EASI clinical signs and body regions, including the head and neck region and clinical sign of lichenification, compared with placebo. ClinicalTrials.gov identifier: ADvocate 1 (NCT04146363) and ADvocate 2 (NCT04178967).

Efficacy and safety of dupilumab with concomitant topical corticosteroids in Japanese pediatric patients with moderate-to-severe atopic dermatitis: A randomized, double-blind, placebo-controlled phase 3 study

BackgroundWe investigated the efficacy and safety of dupilumab in Japanese patients aged ≥6 months to <18 years old with moderate-to-severe atopic dermatitis not adequately controlled with existing therapies. MethodsIn this randomized, double-blind, phase 3 study, patients received dupilumab (n = 30) or placebo (n = 32) with concomitant topical corticosteroids for 16 weeks, then all patients received dupilumab from 16 to 52 weeks. The primary endpoint was the proportion of patients with ≥75% improvement in Eczema Area and Severity Index (EASI) score from baseline (EASI-75) to Week 16. Key secondary endpoints included changes in EASI score, proportion of patients with investigator global assessment (IGA) scores of 0/1, and changes in worst daily itch numerical rating scale (NRS) scores (evaluated in patients aged ≥6 to <12 years [n = 35]). ResultsAt Week 16, more patients achieved EASI-75 with dupilumab than placebo (43.3% vs 18.8%; P = 0.0304), and the least squares mean (LSM) difference in percent change in EASI scores at Week 16 of dupilumab vs placebo was –39.4% (P = 0.0003). However, no significant difference in the proportion of patients achieving IGA scores of 0/1 at Week 16 with dupilumab versus placebo were seen (10.0% vs 9.4%; P = 0.8476). The percent change in worst daily itch NRS scores at Week 16 was higher with dupilumab (LSM difference: –33.3%; nominal P = 0.0117). Dupilumab was well tolerated; no new safety signals were identified. ConclusionsDupilumab showed consistent efficacy and was well tolerated in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis previously insufficiently controlled with existing therapies.

Total eosinophil count as a biomarker for therapeutic effects of upadacitinib in atopic dermatitis over 48 weeks.

Atopic dermatitis (AD) is a chronic skin disease characterized by type 2-skewed immune responses, and significantly influenced by cytokines dependent on Janus kinases (JAKs). Upadacitinib, a JAK1 inhibitor, is effective for moderate-to-severe AD. This study aims to identify biomarkers that reflect long-term therapeutic effects of upadacitinib 15 mg or 30 mg. A retrospective study from August 2021 to July 2023 included 213 AD patients treated with upadacitinib 15 mg and 70 AD patients with 30 mg. We analyzed eczema area and severity index (EASI), peak pruritus-numerical rating scale (PP-NRS), serum immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), and total eosinophil count (TEC) at weeks 0, 4, 12, 24, 36, and 48 of treatment. Both treatments with upadacitinib 15 mg and 30 mg significantly reduced EASI and PP-NRS scores over week 4 to 48 compared to baseline. Upadacitinib 15 mg or 30 mg treatment significantly decreased TEC compared to baseline through week 4 to 36 or week 4 to 48, respectively. The percent reduction of TEC correlated with those of EASI and PP-NRS through week 4 to 48 of treatment with upadacitinib 15 mg, or through week 12 to 48 with 30 mg, respectively. After adjusting for % reductions of other laboratory markers, the significance of correlations was preserved at weeks 36 and 48 of 15 mg treatment, while at weeks 4 and 36 of 30 mg treatment. The % reduction of TEC correlated with those of EASI and PP-NRS during upadacitinib treatment, indicating its potential as a biomarker reflecting treatment responses to upadacitinib in AD patients. However, the variability of significant correlation during treatment indicates that further inspection is needed for its usefulness in monitoring responses to upadacitinib treatment for AD.

Evaluating the Clinical Meaning of Dermatology Life Quality Index Scores Between Different Phenotypes of Atopic Dermatitis in Patients Before and After Biologic Therapy With Dupilumab.

Background and Objective: Atopic Dermatitis (AD) is the most prevalent inflammatory skin disorder resulting in an intense impact on patients quality of life. The aim of this study is to evaluate the clinical meaning of the DLQI scores documented between different phenotypes of AD patients under biologic therapy with Dupilumab. Method: We conducted a retrospective analysis of 209 patients with AD treated with Dupilumab for 2 years. These patients were categorized into different clinical phenotypes. Severity of the disease was assessed by using the Eczema Area and Severity Index (EASI), Numerical Scale Rating (NRS) for sleep (NRS sleep), pruritus (NRS pruritus) and Dermatology Life Quality Index (DLQI) at baseline and subsequently at 4,12 and 24 months. Results: Our results show that the higher DLQI scores (mean: 18.6, range:9-30) achieved at T0 are associated with a prurigo nodularis AD pattern, while after 24 months (T3) of therapy with Dupilumab, the worst quality of life index results were reported in Flexural and Head-Neck combined clinical phenotypes. Conclusions: Quality of life is probably what matters most as an overall endpoint in AD. Assessing the clinical meaning of DLQI scores across different AD phenotypes could be a further aid when considering decision making factors in patient management.

Sustained Effectiveness of Upadacitinib in Moderate-to-Severe Atopic Dermatitis: A 48-Week Real-World Study.

Clinical trials and real-world studies have shown the effectiveness of upadacitinib for treating rash and pruritus in patients with atopic dermatitis (AD). This study aimed to determine whether the early reduction in rash or pruritus at week 12 of upadacitinib treatment could be maintained at later treatment stages. This retrospective study involved 227 and 73 patients with moderate-to-severe AD treated with 15 and 30 mg upadacitinib daily, respectively. The eczema area and severity index (EASI) scores, peak pruritus numerical rating scale (PP-NRS), and investigator's global assessment (IGA) were analyzed. At week 12, patients were divided into achievers and non-achievers of EASI 75, 90, 100, absolute EASI ≤ 2, IGA0/1, PP-NRS4, or absolute PP-NRS ≤ 1. Achievement rates for each endpoint were assessed at later time points (weeks 24, 36, and 48) in both groups. Week 12 achievers largely maintained their endpoint achievements until week 48, regardless of dosage (15 mg or 30 mg). Week 12 non-achievers saw an increasing achievement rate of EASI 75 until week 48. The initial reduction in rash and pruritus at week 12 persisted until week 48 with upadacitinib treatment, suggesting potential benefits for patients requiring prolonged treatment despite not achieving EASI 75 at week 12.

Matching-Adjusted Indirect Comparison of the Efficacy at Week32 of Tralokinumab and Dupilumab in the Treatment of Moderate-to-Severe Atopic Dermatitis.

Tralokinumab and dupilumab are biological agents licensed for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients who are candidates for systemic treatment. However, no head-to-head studies of their efficacy have been conducted. This study indirectly compared the efficacy of tralokinumab and dupilumab, both in combination with topical corticosteroids (TCS), at week32. An unanchored matching-adjusted indirect comparison was conducted using individual patient data (IPD) from the ECZTRA3 tralokinumab trial and aggregate data from the LIBERTY AD CHRONOS dupilumab trial. IPD were selected by applying inclusion criteria from LIBERTY AD CHRONOS and weighting to match summary baseline characteristics-age, sex, race, body mass index, disease duration, Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Dermatology Life Quality Index (DLQI) and SCORing Atopic Dermatitis index-of patients treated with dupilumab. Week32 outcomes of interest were 50%, 75% or 90% improvements in EASI (EASI-50, EASI-75 and EASI-90), IGA scores of 0 or 1 (IGA0/1), ≥ 4-point improvement in worst daily pruritus numerical rating scale (NRS) score, and mean improvements in DLQI and the Patient Oriented Eczema Measure (POEM). After matching, tralokinumab and dupilumab, both in combination with TCS, showed similar efficacy across clinical response endpoints at week32 (IGA0/1, tralokinumab 49.9% vs dupilumab 39.3%; EASI-50, 78.9% vs 77.5%; EASI-75, 71.5% vs 71.9%; EASI-90, 53.3% vs 56.2%). The mean change from baseline in DLQI was statistically significantly larger in the matched tralokinumab plus TCS population than in the dupilumab plus TCS arm (- 12.1 vs - 10.4, p = 0.005). Changes in POEM and worst daily pruritus NRS were similar in the two groups. The results of this analysis demonstrate that, in combination with TCS, tralokinumab and dupilumab have similar efficacy in the treatment of moderate-to-severe AD at 32weeks of therapy.

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Background: Atopic Dermatitis (AD) is a prevalent inflammatory skin disease whose course is often complicated by the presence of concomitant anxiety and depressive disorders. Dupilumab has been demonstrated to be largely effective in AD. The aims of the present study were to (1) to verify the effectiveness of 2-year dupilumab treatment on the depressive and anxiety symptoms of patients affected by AD and (2) to identify predictors of the persistence of psychiatric symptoms despite maintenance treatment with dupilumab. Methods: A total of 331 patients with severe AD were assessed at baseline and at different times over 2 years by a large set of rating scales, including the Eczema Area and Severity Index (EASI), the Hospital Anxiety and Depression Scale (HADS), and the Dermatology Life Quality Index (DLQI). Paired sample t-tests were performed to verify the effectiveness of dupilumab on the severity of AD and mental health items. Two binary logistic regression models were then used to identify the predictors of the persistence of clinically significant depression and anxiety, defined by a score ≥ 8 on each sub-scale of the HADS. Results: After 2 years of treatment with dupilumab, the patients benefited, showing a significant improvement in both the dermatological disease and comorbid depression/anxiety (p < 0.001 for all scales). Overall, 17.5% and 13% of patients, respectively, reported residual depressive and anxiety symptoms after the 2-year treatment with dupilumab. The baseline predictors of the persistence of clinically significant depressive symptoms after the 2-year treatment with dupilumab were found to be a higher body mass index (BMI) (p = 0.012), a lower impact of dermatological disease on quality of life (p = 0.015), and more severe depressive symptoms (p < 0.01), while for anxiety, the only predictor was found to be female gender (p = 0.03). Conclusions: Using a multidisciplinary approach, at baseline, dermatologists should more closely monitor patients who are at a greater risk of maintaining residual psychiatric symptoms despite therapy, such as those with more severe depressive symptoms and those who are overweight.

Effects of abrocitinib on pruritus and eczema symptoms and tolerance in patients with moderate‑to‑severe atopic dermatitis in randomized, double‑blind and placebo‑controlled trials: A systematic review and a meta‑analysis.

Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In addition, abrocitinib inhibits JAK1 signaling in sensory neurons to alleviate acute and chronic pruritus during AD. However, substantial variations in efficacy and safety risks remain due to variations in doses applied in clinical use. Therefore for the present study, differences in the efficacy and tolerability of 100 and 200 mg abrocitinib for treating pruritus and eczema symptoms in patients with moderate-to-severe AD were evaluated compared with placebo. Specifically, randomized controlled trials (RCTs) of abrocitinib compared with placebo for the treatment of moderate-to-severe AD were searched on Pubmed, E.B. Stephens Company, China National Knowledge Infrastructure, Wanfang Medical network, Web of Science and related Clinical Trials Registry up to November 2023. In total, two researchers evaluated the quality of the included literature according to the Cochrane Handbook of Systematic Reviews. RevMan 5.3 software was used to conduct a meta-analysis of the efficacy and safety indicators in a cross-comparison of the effects exerted by placebo and 100 and 200 mg abrocitinib. A total of 1,825 patients with moderate-to-severe AD were included across five double-blind, placebo RCTs. Compared with the placebo group, during the double-blind trial period, significant improvements were observed in the investigator's global assessment score, response rate of eczema area and severity index (EASI)-50, EASI-75, EASI-90 and pruritus numerical rating scale (P-NRS) in the 100 and 200 mg abrocitinib groups (P<0.05). However, pairwise control analysis of the 100 and 200 mg group yielded significant differences (P<0.05) in all of the aforementioned therapeutic indicators except for the P-NRS score. In terms of safety, compared with the placebo group, there were significantly higher incidence of nausea, upper respiratory tract viral infection, infections and infestations in the 100 mg abrocitinib group (P<0.05). In addition, there were significantly higher incidence of nausea, gastrointestinal disorder, headache and dizziness in the 200 mg group (P<0.05). There were also significant differences in the incidence of nausea, gastrointestinal disorder and dizziness between the 100 and 200 mg groups (P<0.05). For patients with moderate-to-severe AD, oral administration of 100 or 200 mg abrocitinib once/day was concluded to ameliorate skin pruritus and eczema symptoms to varying degrees, with the efficacy significantly superior at the 200 mg dose. However, the risk of a number of adverse reactions, such as headache, dizziness, nausea and gastrointestinal dysfunction, is also significantly increased. Therefore, patients should be made aware of the risk of adverse drug effects prior to the administration of long-term high abrocitinib doses. Furthermore, large-scale, multi-center, rigorous clinical trials remain necessary to validate the findings from the present study.

Clinical efficacy and safety of autologous serum intramuscular injection in patients with mild-to-moderate atopic dermatitis: a prospective, open-label, uncontrolled study

Background: Autologous blood therapy (ABT) has been used to treat atopic dermatitis (AD) for over a century, even though evidence supporting its efficacy is lacking. We aimed to investigate the effectiveness and safety of autologous serum intramuscular injection (ASIM), which is a modified form of ABT, in treating mild-to-moderate AD. Methods: This study was a 12-week, open-label, prospective, uncontrolled trial. Following a 4-week run-in period, 22 out of 25 screened patients received ASIM once a week for 4 weeks in conjunction with standard treatment. The primary outcome measure was the Eczema Area and Severity Index (EASI), while the secondary outcomes included the Scoring Atopic Dermatitis (SCORAD) score, Dermatologic Life Quality Index (DLQI), and patient ratings of pruritus, sleep difficulty, disease status, and treatment effectiveness. Safety parameters were also assessed. Results: EASI scores showed a non-statistically significant trend toward improvement during ASIM intervention. Patients with at least a 50% improvement in the EASI score at 4 weeks were older and had lower peripheral eosinophil counts (p&lt;0.05). Secondary endpoints, including the SCORAD score, pruritus, sleep difficulty, and DLQI, demonstrated statistically significant improvements at week 4 compared to baseline (p&lt;0.05). No significant adverse reactions were observed. Conclusions: This pioneering study suggests that repeated ASIM may improve the clinical symptoms of mild-to-moderate AD, particularly in terms of pruritus and overall quality of life. However, further research with a larger sample size is required to establish the clinical significance of these findings.

Roflumilast Cream 0.15% in Patients with Atopic Dermatitis: Individual Patient Response from the Pooled INTEGUMENT-1 and INTEGUMENT-2 Phase 3 Trials

Introduction: Roflumilast cream 0.15% is a highly selective phosphodiesterase 4 inhibitor under investigation as a once-daily, nonsteroidal treatment for atopic dermatitis (AD). Pooled safety and efficacy results of two Phase 3 clinical trials (INTEGUMENT-1 and INTEGUMENT-2) in patients with AD have been presented previously. Here we present individual patient responses on the Eczema Area and Severity Index (EASI), which is used to assess disease severity in clinical trials. Methods: INTEGUMENT-1 and INTEGUMENT-2 were identical, randomized, double-blind, vehicle-controlled, 4-week trials of once-daily roflumilast cream 0.15% in patients aged ≥6 with AD (body surface area [BSA] affected: ≥3%). Patients were randomly assigned 2:1 to roflumilast cream 0.15% or vehicle cream. The primary efficacy endpoint was Validated Investigator Global Assessment for AD (vIGA-AD) Success (score of 0 [Clear] or 1 [Almost Clear] plus ≥2-point improvement from baseline, assessed on a five-point scale ranging from 0 to 4 [Severe]) at Week 4. EASI was assessed as a secondary endpoint. Safety and tolerability were also evaluated. Results: In total, 884 patients received roflumilast 0.15% cream and 453 patients received vehicle cream. Baseline characteristics and demographics were similar between treatment groups. Significantly more roflumilast- than vehicle-treated patients achieved vIGA-AD Success (31.3% versus 14.1%; P&lt;0.0001) and vIGA-AD of Clear or Almost Clear (41.1% vs. 21.4%; P&lt;0.0001) at Week 4. Roflumilast treatment significantly improved itch by 24 hours after first application (P&lt;0.0001). At the first post-treatment timepoint evaluated (Week 1), 84.9% of roflumilast-treated patients had a measurable improvement in EASI. By Week 4, 91.5% of patients had a measurable improvement in EASI. Differences favoring roflumilast were also observed at Week 4 for percentages of patients achieving a 50% reduction in EASI (69.2% vs. 44.4%; P&lt;0.0001), 75% reduction (44.5% vs. 21.2%, P&lt;0.0001), 90% reduction (22.4% vs 8.6%; P&lt;0.0001), and 100% reduction (9.8% vs 4.8%; P&lt;0.002). Roflumilast cream had low rates of application-site adverse events (AEs), treatment-related AEs, and discontinuations due to AEs, comparable with vehicle. On local tolerability assessments, &gt;95% of investigators reported no evidence of irritation at any time point and &gt;90% of patients reported no or mild sensation after applying roflumilast cream on patient-rated local tolerability assessments. Conclusions: Roflumilast cream 0.15% provided greater improvement in vIGA-AD Success, vIGA-AD of Clear or Almost Clear, itch, and EASI versus vehicle in patients with AD in two Phase 3 trials. Among patients treated with roflumilast cream 0.15%, 91.5% demonstrated an improvement in EASI score by Week 4. Safety and tolerability were favorable, with &gt;90% of roflumilast- and vehicle-treated patients reporting no or mild sensation at the application site at any timepoint. Sponsored by Arcutis Biotherapeutics, Inc. ClinicalTrials.gov Identifiers: INTEGUMENT-1 [NCT04773587]; INTEGUMENT-2 [NCT04773600]

Factors Associated with Persistent Efficacy of Abrocitinib without Flare: A Multivariable Analysis of the JADE-REGIMEN Study

Introduction: JADE REGIMEN (NCT03627767) was conducted to evaluate the feasibility of continual, reduced dose or withdrawal of abrocitinib after induction of response in patients with moderate-to-severe atopic dermatitis (AD). This post hoc analysis evaluated patient factors associated with a higher probability of persistent clinical response with abrocitinib, without flare, during a 40-week maintenance period.Methods: Data were analyzed from patients who responded to abrocitinib 200 mg induction therapy (12 weeks) and were randomly assigned to receive abrocitinib (200 or 100 mg) or placebo in the maintenance period (40 weeks). A multivariable logistic regression model with fixed and random effects was fit to determine factors associated with not experiencing flare by week 52. Fixed effects (factors) considered were randomly allocated treatment, age (&lt;18 vs ≥18 years), race, weight, prior use of systemic agents, AD duration, onset of response in induction (early vs late), Investigator’s Global Assessment score at randomization, body surface area (BSA, ≤50% vs &gt;50%) at baseline, and percentage change in Eczema Area and Severity Index (EASI) at randomization. Backward elimination and stepwise model selection procedures were applied with entry and exit criteria based on a P value threshold of 5%.Results:1233 patients received abrocitinib 200 mg in the induction period. By week 12, 798 (64.7%) achieved a response and were randomly assigned to receive maintenance treatment for 40 weeks. In total, 356 patients (44.6%) experienced a protocol-defined flare: 16.5% (200 mg), 39.6% (100 mg), and 77.5% (placebo). After model selection, the analysis identified continuation of treatment with abrocitinib 200 mg (odds ratio [OR], 19.51; 95% CI, 11.28-33.75) or reduced-dose abrocitinib 100 mg (5.27; 3.29-8.46) as the greatest predictors of not experiencing flare during maintenance. Not having previously used systemic agents (OR, 1.53; 95% CI, 1.09-2.14), lower baseline BSA (1.55; 1.10-2.17), and greater percentage reduction of EASI during induction (1.35; 1.15-1.59) were also associated with not experiencing flare.Conclusions: Multivariable analysis of JADE REGIMEN indicated that maintenance treatment with abrocitinib in patients with AD reduced the risk for flare in a dose-dependent manner. Other factors associated with maintaining response to treatment without flare included no previous exposure to systemic agents, lower extent of BSA involvement at baseline, and greater percent change in EASI during induction. These findings may assist clinicians with abrocitinib dosing decisions in the future.

Efficacy Outcomes in Clinical Trials of Atopic Dermatitis Treatments: A Systematic Literature Review

Introduction: Complete skin clearance is a key atopic dermatitis (AD) treatment goal. Treatment efficacy in AD trials is evaluated using a range of clinical measures with the Investigator’s Global Assessment (IGA) as a key endpoint. Multiple and varied forms of the IGA scale are utilized across trials, including the Investigator’s Static Global Assessment and the Validated Investigator Global Assessment for ADTM. IGA scores usually range from 0 (clear) to 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe), but contain differences in detail assessed. Efficacy endpoints using IGA scales include achieving IGA=0 or 1 with ≥2-point improvement from baseline, or IGA=0. The Eczema Area and Severity Index (EASI) and achievement of ≥75% or ≥90% improvement from baseline (EASI75 and EASI90) are additional gold-standard measurements.&#x0D; Objective: To compare differences in efficacy outcomes in recent clinical trials of FDA-approved AD treatments for adults and children.&#x0D; Methods: A systematic literature search was conducted using MEDLINE, Embase, Cochrane Library, and hand search to identify AD trials published in English language between January 1, 2016 and August 16, 2023. Trials could include patients with any severity of AD who were treated with topical therapies (crisaborole, ruxolitinib), injectable systemics (dupilumab, tralokinumab), or oral systemics (upadacitinib, abrocitinib) according to approved indications. Efficacy outcomes of IGA=0 or 1 with ≥2-point improvement, IGA=0, EASI75, and EASI90 were categorized and summarized by AD severity, treatment type, and age groups in the trials.&#x0D; Results: Of 50 publications identified, 40 (80%) reported randomized controlled trials, 2 (4%) single-arm trials, and 8 (16%) open-label extension trials. By patient age groups, 11 publications were on children (&lt;12 years), 8 on adolescents (12–17 years),15 on patients ≥12 years, and 17 on adults (≥18 years). Moderate to severe AD was the most frequently studied severity (38/50 publications), of which all trials were either as systemic monotherapy or systemic therapy combined with a topical. Topical monotherapy for mild to moderate AD only was reported in 8/50 publications. For topicals, achievement of IGA=0 (clear) was not reported for any age group, and no trials reported EASI90 for children &lt;12 years. For injectable systemics, no outcome was reported for IGA=0 (clear) in children &lt;12 years. For oral systemics, no outcomes were reported for children &lt;12 years.&#x0D; Conclusions: This literature search of AD trial publications on FDA-approved treatments from 2016 onwards revealed several gaps in available outcomes data. There were no trials that assessed a topical therapy for moderate to severe AD, and complete disease clearance (IGA=0) was not demonstrated for any topicals. The findings reinforce the unmet need for a topical AD treatment that can provide high efficacy including complete clearance without restriction based on age or disease severity.&#x0D; Funding Support: Dermavant Sciences, Inc.

Vitamin D deficiency and atopic dermatitis severity in a Bangladeshi population living in East London: A cross‐sectional study

AbstractBackgroundAtopic eczema is a common, chronic, inflammatory skin condition with considerable heterogeneity. South Asian people living in the UK frequently have low serum vitamin D3 (25(OH)D3), and those with atopic disease can present with severe eczema. The association between vitamin D deficiency and eczema severity, and the role of vitamin D supplementation in atopic eczema is inconsistent, and under‐researched in people with Asian ancestry.ObjectivesThis cross‐sectional study investigates the association between serum 25(OH)D3 and eczema severity in a cohort of South Asian children and young adults living in London.MethodsEligible participants were Bangladeshi children and young adults aged 0–30 years with eczema, living in London and participating in the Tower Hamlets Eczema Assessment study. Data was collected via parent/patient self‐reporting, clinical history and examination, and hospital databases. 25(OH)D3 levels were documented retrospectively, if available, from hospital databases. Eczema severity was classified by Eczema Area and Severity Index (EASI) score less than or greater than 10 (clear‐mild vs. moderate‐severe). Multivariate logistic regression was used to adjust for confounding factors.Results681 participants were included in analyses. 25(OH)D3 results were available for 49.6% (338/681), 84.3% of which had deficient or insufficient lowest 25(OH)D3. Lowest 25(OH)D3 was inversely correlated with EASI score (Spearman's rank R2 = −0.24, p &lt; 0.001). 26.1% (178/681) had EASI &gt;10 and a lower median lowest and nearest 25(OH)D3. After adjustment for confounding EASI &gt; 10 was significantly associated with a lowest 25(OH)D3 &lt; 25 (OR 3.21, 95%CI 1.35, 8.60), use of mild‐moderate potency topical steroid on the face and neck (OR 3.11, 95%CI 1.86, 5.31), calcineurin inhibitor on the face and neck (OR 2.79, 95% CI 1.26, 6.10) and potent – very potent topical steroid on the face and neck (OR2.23, 95%CI 1.02, 4.77) and body (OR 2.11, 95%CI 1.18, 3.87).DiscussionVitamin D plays a role in modulation of proteins required for skin barrier function and regulation of the innate immune system, suggesting 25(OH)D3 deficiency contributes to skin inflammation. This study demonstrates a relationship between 25(OH)D3 deficiency and worse eczema severity in a cohort of South Asian children and young adults.

Effectiveness of Dose Increase in Upadacitinib from 15 mg to 30 mg for Patients with Moderate-to-Severe Atopic Dermatitis: A Real-World Clinical Practice in Japan.

Atopic dermatitis is characterized by persistent eczema and pruritus. Janus kinase inhibitors, including upadacitinib, are effective treatments for moderate-to-severe atopic dermatitis. If patients do not respond well to a certain dose of a Janus kinase inhibitor, increasing the dose may improve their treatment responsiveness. We assessed the outcomes of a dose increase in upadacitinib from 15 mg to 30 mg for Japanese patients with moderate-to-severe atopic dermatitis. In 23 patients who showed insufficient responses to upadacitinib 15-mg treatment, the dose of upadacitinib was increased to 30 mg. We evaluated total Eczema Area and Severity Index (EASI), EASI on the head and neck, trunk, upper, or lower limbs, EASI of erythema, edema/papulation, excoriation, or lichenification, and Peak Pruritus Numerical-Rating Scale at baseline (onset of upadactinib 15 mg), week 0 (time of increase), and weeks 4 and 12 after the increase. Total EASI, EASI on each anatomical site, EASI of each clinical sign, and Peak Pruritus Numerical-Rating Scale were markedly reduced at weeks 4 or 12 compared with week 0. After the dose increase, the achievement rates of EASI 75 and EASI 90 significantly improved; EASI 75 4.3%, 68.2%, and 66.7%; EASI 90 0%, 18.2%, and 38.1% at weeks 0, 4, and 12, respectively. These results suggest that upadacitinib 30 mg can ameliorate rash and pruritus insufficiently improved by upadacitinib 15 mg, and that the dose increase to 30 mg may be considered as atreatment option for patients with atopic dermatitis with a limited response to upadacitinib 15 mg.

Real-world effectiveness and safety of abrocitinib in 12 Japanese patients with atopic dermatitis and transcriptome analysis with peripheral blood.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by recurrent, pruritic, and localized eczema. Various types of new drugs have been recently investigated for treating AD. The efficacy and safety of abrocitinib in treating AD has been reported in clinical trials, but the real-world data from Japan has not been reported. Herein, we analyzed 12 Japanese patients with AD treated with 100 mg of abrocitinib using our real-world data. We also performed transcriptome analysis with peripheral blood to investigate the effects of abrocitinib on cytokine expressions and inflammatory pathways in AD from three patients. This study included patients with moderate to severe AD treated with abrocitinib at Gunma University Hospital, Japan. All patients were systemic treatment-naïve. All patients received a 100-mg dose of abrocitinib daily, and used strong or very strong topical steroids and moisturizers. The Eczema Area and Severity Index (EASI) response analysis revealed that after 4 weeks, 25% (three of 12) of the cases reached a 75% reduction in the EASI score (EASI-75) and a 90% reduction in the EASI score (EASI-90). After 12 weeks, 83.3.% (10 of 12), 41.6% (five of 12), and 16.7% (two of 12) of the patients reached EASI-50, a 75% reduction in the EASI score (EASI-75), and EASI-90. Peak Pruritus Numerical Rating Scale was achieved in nine patients (75%) at week 12. The most frequent adverse reaction was acne (six cases [50%]). Gene Ontology pathway analysis using Differentially expressed genes from RNA sequencing analysis revealed attenuation of defense responses to biotic stimulus, virus, and cytokines. Th2 cytokine expression was not suppressed, but several chemokines, especially CXCL1, were suppressed by abrocitinib treatment. Our results indicate abrocitinib as a fast-acting and highly antipruritic agent that is effective for moderate skin eruptions.

Cost per NNT for upadacitinib in the treatment of patients with moderate-severe atopic dermatitis in Italy

Background: Targeted systemic therapies, including abrocitinib, baricitinib, dupilumab, tralokinumab and upadacitinib, are new treatments for moderate to severe atopic dermatitis (AD). We evaluated the efficacy and the costs of these targeted systemic therapies in the treatment of adult patients with moderate to severe AD. Methods: The clinical efficacy was assessed considering the results of a previous network meta-analysis (NMA). The analysis involved five therapies approved in Italy for the treatment of moderate to severe AD: abrocitinib (ABR), baricitinib (BAR), dupilumab (DUP), tralokinumab (TRA) and upadacitinib (UPA). According to the NMA, the cost of the treatment was based on the number of administrations dispensed at 16 weeks and the clinical efficacy was measured by the number needed to treat (NNT) compared to placebo using the improvement ≥ 75% (EASI-75) or ≥ 90 (EASI-90) from baseline of the eczema area and severity index (EASI). Only the ex-factory price of the targeted systemic therapies was considered. The cost per NNT was adopted as a cost-effectiveness indicator. Results: At 16 weeks, the cost per NNT based on EASI-75 was lower for UPA 15 mg (€ 6,384.00) compared to BAR 4 mg (€ 11,619.73) and 2 mg (€ 14,524.66), ABR 100 mg (€ 16,265.22), DUP 300 mg (€ 16,115.04) and TRA 300 mg (€ 31,710.24). UPA 15 (€ 8,512.00) also showed the lower cost per NNT based on EASI-90 at 16 weeks compared to BAR 4 mg (€ 14,788.75) and 2 mg (€ 20,862.70), ABR 100 mg (€ 25,922.69), DUP 300 mg (€ 25,992.00) and TRA 300 mg (€ 41,067.36). Conclusions: The findings show that upadacitinib is the most cost-effective option (cost per NNT) for the treatment of moderate to severe atopic dermatitis.

523 - Efficacy and safety of amlitelimab (an anti-OX40 ligand antibody) in patients with moderate-to-severe atopic dermatitis: 24-week results from a phase 2b trial (STREAM-AD)

Abstract Introduction/Background Targeting and binding OX40 ligand (OX40L) expressed on antigen-presenting cells may inhibit the persistent immune response that drives atopic dermatitis (AD) pathophysiology. Amlitelimab (SAR445229; KY1005) is a potential first-in-class, fully human, non-depleting anti-OX40L monoclonal antibody that blocks OX40L-OX40 interactions and has shown efficacy and an acceptable safety profile in a Phase 2a trial in adults with moderate-to-severe AD. Here, we present 24-week efficacy and safety results (Part 1) from an ongoing dose-ranging Phase 2b trial. The study remains blinded to individual patient data (Part 2 ongoing). Objectives To evaluate the efficacy and safety of amlitelimab in adults with moderate-to-severe AD. Methods STREAM-AD (NCT05131477) is a 52-week, randomised, double-blinded, placebo-controlled Phase 2b monotherapy trial. This study is designed with 2 parts (double-blind throughout): a 24-week treatment period (Part 1, completed and presented here) and a 36-week maintenance/withdrawal period (Part 2, ongoing). Adults (18 to &amp;lt;75 years; n=390) with moderate-to-severe AD were randomised 1:1:1:1:1 to receive subcutaneous amlitelimab Q4W (250 mg with 500 mg loading dose [LD], n=77; 250 mg without LD, n=78; 125 mg without LD, n=77; or 62.5 mg without LD, n=79) or placebo Q4W (n=79). The primary endpoint was percentage change in Eczema Area and Severity Index (EASI) from baseline at Week 16. Key secondary endpoints included percentage change in EASI at Week 24 and percentage of patients with at least 75% reduction from baseline in EASI (EASI-75), percentage of patients with Investigator Global Assessment response of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points (IGA 0/1), and proportion of patients with a weekly average reduction of Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 points from baseline. The primary efficacy analysis included all randomised patients who completed Week 24 or discontinued treatment or study prior to Week 24 visit (n=390), whereas the safety analysis included all treated patients (n=388). Results Treatment with amlitelimab resulted in statistically significant improvements in percentage change in EASI from baseline to Week 16 compared to placebo for all four doses studied. The 250 mg with LD group had the numerically highest response versus placebo at Week 16, with a least-squares mean change from baseline of –32.1% (95% CI: –43.9, –20.3; P&amp;lt;0.0001); the remaining groups without LD had the following responses versus placebo: 250 mg, –27.3 (95% CI: –39.1, –15.6; P&amp;lt;0.0001); 125 mg, –22.2 (95% CI: –34.0, –10.4; P=0.0002); and 62.5 mg, –30.2 (95% CI: –41.9, –18.5; P&amp;lt;0.0001). There were also clinically meaningful improvements in all key secondary efficacy outcome measures, with all amlitelimab dose groups demonstrating nominally significant (P&amp;lt;0.05) efficacy versus placebo for EASI-75, IGA 0/1, and PP-NRS ≥4, except 250 mg (no LD) in IGA 0/1 at Week 16 (P=0.0562). Continued improvements were generally observed through Week 24 in primary and key secondary efficacy outcomes. Amlitelimab was well tolerated across all dose groups, with no safety concerns identified. Conclusions In this dose-ranging Phase 2b trial of amlitelimab in adults with moderate-to-severe AD, amlitelimab demonstrated clinically meaningful efficacy over 24 weeks with an acceptable safety profile across all four dose groups.

551 - Continuous tralokinumab treatment over 4 years in adults with moderate-to-severe atopic dermatitis provides long-term disease control

Abstract Introduction/Background There is a need for additional long-term treatment options for patients with moderate-to-severe atopic dermatitis (AD) that provide sustained disease control with a favorable safety profile. Tralokinumab, a monoclonal antibody that specifically neutralizes interleukin-13, is approved for the treatment of moderate-to-severe AD in multiple countries. Clinical trials of up to 52-wk duration showed that tralokinumab was effective and well tolerated as monotherapy and in combination with topical therapy. ECZTEND (NCT03587805) is an ongoing open-label, 5-yr extension trial investigating the long-term safety and efficacy of tralokinumab ± optional topical corticosteroids (TCS). Objectives To assess the efficacy of long-term tralokinumab treatment, we conducted a post hoc interim subgroup analysis restricted to the largest, most homogenous patient population, with the longest treatment duration. Methods Adult patients with moderate-to-severe AD who were continuously treated with tralokinumab ± optional TCS for 52 wks in the parent phase 3 trials ECZTRA 1 (NCT03131648) or ECZTRA 2 (NCT03160885) and for up to 152 wks in ECZTEND as of data cutoff April 30, 2022, were included. Endpoints included proportion of patients achieving Investigator’s Global Assessment (IGA) score of 0/1 (clear/almost clear skin), at least 75% or 90% improvement in Eczema Area and Severity Index (EASI) relative to parent trial baseline (EASI-75 or EASI-90), EASI ≤7, worst weekly pruritus Numeric Rating Scale (NRS) ≤4, and Dermatology Life Quality Index (DLQI) ≤5. Results are presented using observed data. Sensitivity analyses on patients who completed Wk 152 in ECZTEND (or who withdrew, but were enrolled in the study at least 152 wks prior to the study cutoff) were performed using modified non-responder imputation (mNRI) with discontinuations due to AEs or lack of efficacy imputed as non-responders and a 2-step multiple imputation (MI) for other missing data [Step 1: Missing data up to 1 year in ECZTEND were imputed using a standard regression-based MI method; Step 2: Missing data post 1 year imputed by carrying forward the within-subject area under the curve of days in-response]. Results 347 adult patients with a mean age (SD) of 42.2 (14.5) yrs and a mean EASI (SD) of 30.8 (13.7) at parent trial baseline were included in this analysis. After 4 yrs of total tralokinumab treatment (at Wk 152 in ECZTEND), IGA 0/1 [% (n/N)] was observed in 52.6% (92/175) of patients. EASI-75 {% (n/N) [95% CI]} was achieved in 84.5% (147/174) [78.4, 89.1] of patients as observed, and in 73.4% (254.8/347) [68.6, 78.3] using mNRI. EASI-90 was achieved in 64.4% (112/174) [57.0, 71.1] of patients as observed, and in 53.4% (185.2/347) [47.8, 59.0] using mNRI. Additionally, EASI ≤7 (mild disease) was observed in 84.5% (147/174) of patients, worst weekly pruritus NRS ≤4 (no to mild itch) in 68.0% (119/175), and DLQI ≤5 (no to small effect of AD on quality of life) in 79.0% (128/162) of patients. The safety profile was favorable and consistent with earlier analyses, with no new safety signals arising with continued tralokinumab use. Conclusions Continuous use of tralokinumab ± optional TCS provided long-term disease control over 4 yrs in adult patients with moderate-to-severe AD.