Introduction Les critères d’activité minimale de la maladie (MDA) basés sur un consensus d’experts associent les principes du « treat to target » et de la décision médicale partagée afin d’établir des objectifs optimaux de contrôle de la maladie pour les patients atteints de dermatite atopique (DA).1 Les objectifs de la MDA combinent des résultats rapportés par les cliniciens (ClinROs) : le score EASI (Eczema Area and Severity Index), le SCORAD (SCORing AD), le score IGA (Investigator's Global Assessment) ou le score BSA (Body Surface Area) et des résultats rapportés par les patients (PRO) : le score de prurit maximal WP-NRS (Worst Pruritus Numerical Rating Scale), le score NRS-douleur, le score NRS-sommeil, le score POEM (Patient-Oriented Eczema Measure), l’échelle HADS (Hospital Anxiety and Depression Scale) ou le score DLQI (Dermatology Life Quality Index) avec des seuils ambitieux, comme la réponse EASI 90 et le score NRS-prurit 0/1. Matériel et méthodes À l’aide des données poolées de deux études cliniques de phase 3 randomisées contrôlées versus placebo (Measure Up 1 et 2), l’atteinte des objectifs de la MDA (EASI90 ou NRS prurit 0/1) avec l’upadacitinib en monothérapie a été évaluée aux semaines 16 et 52 (imputation des non-répondeurs) chez les patients atteints de DA modérée à sévère. Résultats À la semaine 16, 42,5 % et 55,9 % des patients traités par upadacitinib 15mg et 30mg respectivement ont atteint à la fois un critère de clinRO et de PRO. Une proportion plus élevée de patients recevant de l’upadacitinib 15mg ou 30mg (53,3 % ou 65,8 % respectivement) a atteint un critère de ClinRO par rapport au placebo (10,0 %). L’atteinte d’un critère de PRO était plus importante chez les patients traités par upadacitinib 15mg ou 30mg (56,4 % ou 69,7 % respectivement) par rapport au placebo (16,6 %). Toutes les valeurs de P à 16 semaines étaient<0,001. Les taux d’atteinte de la MDA ont été maintenus jusqu’à la semaine 52 pour les patients recevant de l’upadacitinib 15mg ou 30 mg : 1 critère de ClinRO (54,2 % ou 59,4 % respectivement), 1 critère de PRO (56,0 % ou 68,6 % respectivement) et 1 critère de ClinRO et de PRO (45,2 % ou 54,5 % respectivement). Discussion Ainsi, le traitement par l’upadacitinib a permis l’atteinte et le maintien de la MDA avec les objectifs optimaux de ClinRO et PRO. Conclusion L’accomplissement de ces objectifs peut optimiser la gestion globale de la maladie chez les patients atteints de DA modérée à sévère.

Abstract Introduction & Objectives Upadacitinib (UPA) is an oral Janus kinase 1 (JAK1) inhibitor approved in multiple countries for the treatment of adolescents and adults with moderate-to-severe atopic dermatitis (AD). Here, we present the efficacy and safety of UPA administered over 140 weeks in an ongoing randomized, double-blinded, multicenter phase 3 study (Measure Up 1, NCT03569293). Materials & Methods Patients (12–75 years) with moderate-to-severe AD were randomized 1:1:1 to receive UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) once daily at baseline. At week 16, PBO-treated patients were re-randomized 1:1 to receive UPA15 (PBO/UPA15) or UPA30 (PBO/UPA30) once daily. Co-primary endpoints were the proportion of patients achieving ≥75% reduction in EASI (EASI 75) from baseline and vIGA-AD of clear (0) or almost clear (1) with ≥2 grades of reduction from baseline (vIGA-AD 0/1) at week 16. A meaningful improvement in itch, defined as a ≥4-point reduction in Worst Pruritus Numeric Rating Scale (ΔWP-NRS≥4), was assessed among patients with baseline WP-NRS≥4. All efficacy endpoints were summarized using the Observed Cases (OC) approach, and no missing data imputation was applied. Safety was assessed by monitoring of serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), and treatment-emergent adverse events of special interest (AESI), which were analysed as exposure-adjusted rates per 100 patient-years (PY). Results Efficacy results were sustained up to week 140 since week 16. Proportions of patients in the UPA15 (205), UPA30 (206), PBO/UPA15 (91), and PBO/UPA30 (94) groups achieving EASI 75 at week 140 were 88.8% (182), 90.3% (186), 83.5% (76), and 89.4% (84), respectively, and for vIGA-AD 0/1 was 63.4% (130), 65.5% (135), 60.4% (55), and 75.5% (71), respectively. Proportions of patients achieving an improvement (reduction) in WP-NRS≥4 from baseline at week 140 were 68.0% (136), 70.5% (146), 71.3% (62), and 81.3% (74) respectively. Overall, the rates of AESIs were similar across treatment groups, which aligned with prior reports at earlier time points. Both UPA15 and UPA30 were well-tolerated in all patients, and no new safety signals were observed compared to the known safety profile of UPA. Data from two additional pivotal studies will be available at the time of presentation. Conclusion In this interim analysis, sustained skin clearance and itch and a consistent safety profile were observed with UPA 15 mg and UPA 30 mg across 140 weeks in adolescent and adult patients with moderate-to-severe AD.

The consensus-based minimal disease activity (MDA) criteria combine treat-to-target principles with shared decision-making to establish optimal disease control targets for patients with atopic dermatitis (AD).1 MDA targets encompass combinations of clinician-reported outcomes (ClinROs: Eczema Area and Severity Index [EASI], SCORing AD, Investigators' Global Assessment, and body surface area) and patient-reported outcomes (PROs: Worst Pruritus Numerical Rating Scale [NRS], Pain NRS, Sleep NRS, Patient-Oriented Eczema Measure, Hospital Anxiety and Depression Scale, and Dermatology Life Quality Index) with stringent thresholds, such as EASI 90 and Pruritus NRS 0/1.1 Using integrated data from 2 phase 3 randomized controlled trials (Measure Up 1 and 2), we assessed the treatment effect of upadacitinib monotherapy on achieving MDA at weeks 16 and 52 (nonresponder imputation) among patients with moderate-to-severe AD. At week 16, a higher proportion of patients receiving upadacitinib 15 mg|30 mg (53.3%|65.8%) achieved ≥1 ClinRO target vs placebo (10.0%). Achievement of ≥1 PRO target was greater among patients treated with upadacitinib 15 mg|30 mg (56.4%|69.7%) vs placebo (16.6%). Similarly, attainment of ≥1 ClinRO AND ≥1 PRO target was greater with upadacitinib 15 mg|30 mg (42.5%|55.9%) vs placebo (6.4%). All 16 week P values <.001. Rates of MDA achievement were maintained through week 52 for patients receiving upadacitinib 15 mg|30 mg: ≥1 ClinRO target (54.2%|59.4%), ≥1 PRO target (56.0%|68.6%), and ≥1 ClinRO AND ≥1 PRO target (45.2%|54.5%). Thus, upadacitinib treatment demonstrated achievement and maintenance of MDA with ClinRO and PRO optimal targets; achievement of these targets may optimize overall disease management in patients with moderate-to-severe AD.

La dermatite atopique (DA) est une dermatose inflammatoire chronique multidimensionnelle qui peut provoquer des symptômes cutanés sévères et un prurit intense qui affectent fortement la qualité de vie (QdV) des patients. MEASURE-AD était une étude transversale menée dans 28 pays visant à évaluer le fardeau multidimensionnel de la DA chez les patients qui recevaient ou étaient éligibles à un traitement systémique. Dans cette étude, ont été analysées les associations entre la QdV rapportée par les patients et les mesures de sévérité avec le fardeau de la maladie chez les patients adultes inclus dans l’étude MEASURE-AD. Des patients atteints de DA âgés de ≥ 12 ans ont été recrutés entre décembre 2019 et décembre 2020. Seuls les patients âgés de ≥ 18 ans ont été inclus dans cette analyse. Les patients ont été stratifiés en fonction de l’effet rapporté par les patients sur la QdV évaluée à l’aide du score DLQI et la sévérité de la maladie évaluée à l’aide des scores POEM et ADerm-SS TSS-7. Le fardeau clinique a été évalué à l’aide du score EASI et de l’échelle WP-NRS. Le fardeau socioéconomique a été évalué à l’aide du score WPAI-AD incluant : absentéisme, présentéisme, altération de la productivité globale du travail et altération de l’activité. Parmi les 1434 patients, l’âge moyen était de 39,1 ans, 52 % étaient des hommes et 61 % (n = 868) travaillaient. Les scores EASI et WP-NRS étaient inférieurs chez les patients ayant des score DLQI, POEM et ADerm-SS TSS-7 plus faibles (p < 0,0001). De même, l’altération de la productivité globale du travail était réduite chez les patients ayant des scores DLQI, POEM et ADerm-SS TSS-7 plus faibles (p < 0,0001). Les tendances en matière d’absentéisme, de présentéisme et d’altération de l’activité professionnelle étaient similaires à celles observées pour l’altération de la productivité globale du travail (p < 0,0001). Une meilleure QdV et des scores de sévérité de la maladie plus bas étaient associés à un fardeau clinique et à une altération plus faibles dans cette analyse des données en vie réelle de 1434 patients adultes atteints de DA.

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

Abstract Atopic dermatitis (AD) is characterized by intense itch and symptoms that adversely impact quality of life (QoL). Upadacitinib is a selective Janus kinase-1 inhibitor approved for moderate-to-severe AD. We assessed the effect of once daily oral upadacitinib (15 or 30 mg), with or without concurrent topical corticosteroid treatment, on patient-reported outcomes for adults and adolescents with moderate-to-severe atopic dermatitis during the double-blind, placebo-controlled phase 3 clinical trials, Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422) and AD Up (NCT03568318). Assessments included itch (Worst Pruritus Numerical Rating Scale), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient Oriented Eczema Measure) and sleep, daily activities and emotional state (AD Impact Scale). Post hoc analysis of 2240 adults and 344 adolescents randomized patients was performed. By Week 2, more patients receiving upadacitinib achieved a clinically relevant response in itch, skin pain, symptom severity, symptom frequency, sleep, daily activities and emotional state vs. placebo across studies among adults (upadacitinib 15 mg: 30.8–87.3%; upadacitinib 30 mg: 38.0–89.9%; placebo: 2.1–43.1%; nominal P < 0.001 for all comparisons) and adolescents (upadacitinib 15 mg: 19.4–82.9%; upadacitinib 30 mg: 35.3–97.6%; placebo: 0–41.0%; nominal P < 0.05 for 37/42 comparisons). These trends continued through week 16 where response rates for all outcomes improved with upadacitinib vs. placebo in adults (upadacitinib 15 mg: 42.9–80.4%; upadacitinib 30 mg: 60.9–84.6%; placebo: 10.1–38.1%; nominal P < 0.001 for all comparisons) and adolescents (upadacitinib 15 mg: 33.3–78.0%; upadacitinib 30 mg: 50.0–85.7%; placebo: 2.8–43.6%; nominal P < 0.05 for 41/42 comparisons). These findings highlight the rapid, sustained efficacy of once daily oral upadacitinib in improving symptom burden and QoL in adults and adolescents with moderate-to-severe AD.

BackgroundAtopic dermatitis (AD) is a heterogeneous inflammatory skin disease with different clinical phenotypes based on factors such as age, race, comorbidities, and clinical signs and symptoms. The effect of these factors on therapeutic responses in AD has only been scarcely studied and not for upadacitinib. Currently, there is no biomarker predicting response to upadacitinib. ObjectivesEvaluate the efficacy of the oral Janus kinase inhibitor upadacitinib across patient subgroups (baseline demographics, disease characteristics and prior treatment) in patients with moderate-to-severe AD. MethodsData from phase 3 studies (Measure Up 1, Measure Up 2 and AD Up) were utilized for this post hoc analysis. Adults and adolescents with moderate-to-severe AD were randomized to receive once daily oral upadacitinib 15 mg, upadacitinib 30 mg or placebo; patients enrolled in the AD Up study received concomitant topical corticosteroids. Data from the Measure Up 1 and Measure Up 2 studies were integrated. ResultsA total of 2584 patients were randomized. A consistently greater proportion of patients achieved at least 75% improvement in the Eczema Area and Severity Index, a 0 or 1 on the validated Investigator Global Assessment for Atopic Dermatitis, and improvement in itch (including an achievement of a reduction of & GE;4; and score of 0/1 in Worst Pruritus Numerical Rating Scale) with upadacitinib compared with placebo at Week 16, regardless of age, sex, race, body mass index, AD severity, body surface area involvement, history of atopic comorbidities or asthma, or previous exposure to systemic therapy or cyclosporin. ConclusionsUpadacitinib had consistently high skin clearance rates and itch efficacy across subgroups of patients with moderate-to-severe AD through Week 16. These results support upadacitinib as a suitable treatment option in a variety of patients.

BACKGROUND:Research examining associations between the clinician-reported validated Investigator Global Assessment for AD (vIGA-AD) and patient-reported disease burden is sparse. This study aims to evaluate the relationship between vIGA-AD with patient-reported disease severity and quality of life (QoL).METHODS:A cross-sectional analysis was conducted using a September 2021 data cut from the TARGET-DERM AD study, a real-world, longitudinal cohort of children, adolescents, and adults with AD enrolled at 44 academic and community dermatology and allergy sites in the US. Clinical AD severity was measured using vIGA-AD while disease severity and QoL were assessed by the Patient Oriented Eczema Measure (POEM) and (Children’s) Dermatology Life Quality Index (C/DLQI), respectively. Patient characteristics, clinical- and patient reported-outcomes were assessed by stratified POEM and C/DLQI categories using descriptive statistics. Associations with vIGA-AD were evaluated using unadjusted and adjusted ordinal logistic regression and linear regression models.RESULTS:The analysis cohort (n=1,888) primarily consisted of adults (57%), females (56%), and patients with private insurance (63%). Unadjusted analyses suggest that clinical AD severity was associated with age, with more adolescents and adults having moderate/severe vIGA-AD than pediatric patients. Clinical AD severity was also associated with disease severity, with greater POEM scores observed at greater vIGA-AD severity levels (r = 0.496 and 0.45 for adults and pediatrics, respectively). Clinical AD severity and QoL were positively correlated, with greater CDLQI/DLQI scores at greater vIGA-AD severity levels (r = 0.458 and 0.334 for DLQI and CDLQI, respectively). After adjusting for demographics and other risk factors, vIGA-AD continued to show significant associations with POEM and DLQI/CDLQI. Compared to patients with clear/almost clear disease, adults and pediatrics with moderate-to-severe AD were 8.19 and 5.78 times as likely to be in a more severe POEM category, respectively. Similarly, compared to patients with clear/almost clear disease, adults and pediatrics with moderate/severe AD were 6.69 and 3.74 times as likely to be in a more severe DLQI/CDLQI category. Adjusted linear regression analyses of DLQI in adults showed significant differences by vIGA-AD level, with mild AD and moderate/severe AD associated with a 2.26-point and 5.42-point greater DLQI relative to clear/almost clear AD.CONCLUSIONS:In this real-world study of patients with AD, greater clinician-reported disease severity is positively correlated with higher patient-reported disease severity and lower QoL. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.7473 Access Supplementary Material here Citation: Guttman-Yassky E, Bar J, Rothenberg Lausell C, et al. Do atopic dermatitis patient-reported outcomes correlate with validated investigator global assessment? Insights from TARGET-AD registry. J Drugs Dermatol. 2023;22(4):344-355. doi:10.36849/JDD.7473.

Abstract Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense itch and eczematous skin lesions that can impact individuals at any age across any area of the body. There is a need for safe treatments for AD that provide rapid itch relief and skin clearance and that are suitable for long-term use. Upadacitinib is a selective, reversible oral Janus kinase 1 (JAK1) inhibitor, which is approved in multiple countries for the treatment of adolescents and adults with moderate-to-severe AD. The current analysis assessed the long-term safety for up to 4 years of upadacitinib 15 and 30 mg in adolescents and adults with moderate-to-severe AD, using integrated data from three ongoing global pivotal phase 3 studies. The Measure Up 1, Measure Up 2, and AD Up studies are ongoing pivotal phase 3, randomized, placebo-controlled, multicenter studies evaluating the safety and efficacy of upadacitinib 15 mg and upadacitinib 30 mg in adolescents and adults with moderate-to-severe AD. Patients were randomized 1 : 1 : 1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg or placebo once daily alone (Measure Up 1 and Measure Up 2) or with concomitant topical corticosteroids (AD Up). At Week 16, patients receiving upadacitinib 15 or 30 mg during the double-blinded period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were re-randomized 1 : 1 to receive either upadacitinib 15 or 30 mg in the BE period (upadacitinib treatment for up to 260 weeks). A total of 2693 adults and adolescents (upadacitinib 15 mg, 1340; upadacitinib 30 mg, 1353) who received at least one dose of upadacitinib were included in the integrated analysis. Treatment-emergent adverse events of special interest (AESI) were analysed as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different durations of follow-up. Upadacitinib was well tolerated by both adults and adolescents. For all patients, rates of AESIs were similar at the 1-year analysis and up to 4-year analysis for upadacitinib (15 mg/30 mg) for: serious infections, 2.3 and 2.2/2.8 and 2.8; opportunistic infections, 1.6 and 1.8/1.9 and 2.4; active tuberculosis, <0.1/<0.1 at both time points; herpes zoster, 3.5 and 3.1/5.2 and 5.8; nonmelanoma skin cancer (NMSC), 0.3 and 0.4/0.4 and 0.3; malignancy excluding NMSC, 0.1 and 0.4/0.5 and 0.3; and adverse events leading to death, 0 and 0/<0.1 and <0.1. Rates of adjudicated major adverse cardiovascular events (MACE) were 0.1 and <0.1/<0.1 and <0.1, and for venous thromboembolic events (VTE) were <0.1 for both doses at the 1-year analysis and up to 4-year analysis. Rates of gastrointestinal perforations were 0 for both doses at both timepoint analyses. Rates of serious infections remain low (<3.0 E/100 PY). Based on the integrated analysis of long-term safety data for up to 4 years, rates of AESIs remained low throughout a longer duration of treatment with upadacitinib 15 or 30 mg among adults and adolescents with moderate-to-severe AD. No new safety risks were observed. Findings of the current safety analysis continue to support a favorable benefit-risk profile of upadacitinib in the treatment of adults and adolescents with moderate-to-severe AD for up to 4 years of treatment.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease that can be debilitating, impacting all body areas, including the genital region. Genital AD results in impairments in daily activity levels, sexual function and sleep, contributing to impaired quality of life in patients with moderate-to-severe AD. Upadacitinib (UPA) is a selective oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 vs. JAK2, JAK3 and tyrosine kinase 2, indicated for the treatment of moderate to severe AD. The SCORing Atopic Dermatitis (SCORAD) measure assesses the extent and severity to which a body area is affected, as well as itch and sleeplessness due to AD. In this post-hoc analysis of the Measure Up 1 and Measure Up 2 studies, we evaluated the proportion of patients whose genital AD resolved with UPA 15 mg or UPA 30 mg compared with placebo. Measure Up 1 and 2 are phase 3 multicenter, randomized, double-blind studies comparing the safety and efficacy of UPA 15 mg and UPA 30 mg to placebo in adolescent and adult patients with moderate-to-severe AD. Patients were randomized to oral once daily UPA 15 mg, UPA 30 mg or placebo. The current study assessed the proportion of patients with genital involvement at baseline who achieved genital AD resolution at week 2 and week 16 based on data collected from the SCORAD. Non-responder imputation was used. Of the 1679 participants, 239 (14.2%) had genital AD at baseline and were randomized to UPA 15 mg (n = 77), UPA 30 mg (n = 86) or placebo (n = 76). More participants with genital involvement vs. those without were male (61.1% vs. 54.1%), ≥18 years old (92.1% vs. 85.5%), and severe according to the Validated Investigator Global Assessment Scale for Atopic Dermatitis (66.9% vs. 47.2%) at baseline. On average, participants with genital involvement at baseline also reported greater disease duration (25.0 vs. 22.8 years) and higher Dermatology Life Quality Index (DLQI) scores (19.2 vs. 16.3). At week 2, the proportion of patients whose genital AD was resolved was 70.1% of the UPA 15 mg group, and 82.6% of the UPA 30 mg group, both of which were greater than the placebo group (31.6%; P < 0.001). At week 16, the proportion of patients whose genital AD was resolved increased in the UPA 15 mg (80.5%) and UPA 30 mg (83.7%) groups, but not in the placebo group (28.9%) which remained lower than both groups (P < 0.001). More patients with moderate-to-severe AD achieved resolution of their genital AD with UPA 15 mg or 30 mg monotherapy daily compared to placebo, with >70% rapidly achieving genital AD resolution after 2 weeks and >80% after 16 weeks of UPA treatment. In addition to overall improvements in moderate-to-severe AD with UPA, resolution of genital AD may correspond to improvements in sexual functioning, reductions in sleeplessness and greater quality of life. These findings underscore the importance of considering genital involvement when assessing the burden of AD to comprehensively inform integrated shared decision-making treatment discussions between patients and physicians.

Background: Atopic dermatitis (AD) is characterized by intense itch and symptoms that adversely impact quality of life (QoL). Upadacitinib is a selective Janus kinase-1 inhibitor approved for moderate-to-severe AD. We assessed the effect of once daily oral upadacitinib (15 or 30 mg) on patient-reported outcomes for adults and adolescents during the double-blind, placebo-controlled periods of Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and AD Up (NCT03568318). Assessments included itch (Worst Pruritus Numerical Rating Scale); skin pain and symptom severity (AD Symptom Scale); symptom frequency (Patient Oriented Eczema Measure); and sleep, daily activities, and emotional state (AD Impact Scale). Post-hoc analysis of 2240 adults and 344 adolescents randomized patients was performed. By week 2, more patients receiving upadacitinib achieved a clinically relevant response in itch, skin pain, symptom severity, symptom frequency, sleep, daily activities, and emotional state vs placebo across studies among adults (upadacitinib 15 mg: 30.8-87.3%; upadacitinib 30 mg: 38.0-89.9%; placebo: 2.1- 43.1%; nominal P<.001 for all comparisons) and adolescents (upadacitinib 15 mg: 19.4-82.9%; upadacitinib 30 mg: 35.3-97.6%; placebo: 0-41.0%; nominal P<.05 for 37/42 comparisons). These trends continued through week 16 where response rates for all outcomes improved with upadacitinib vs placebo in adults (upadacitinib 15 mg: 42.9-80.4%; upadacitinib 30 mg: 60.9-84.6%; placebo: 10.1- 38.1%; nominal P<.001 for all comparisons) and adolescents (upadacitinib 15 mg: 33.3-78.0%; upadacitinib 30 mg: 50.0-85.7%; placebo: 2.8-43.6%; nominal P<.05 for 41/42 comparisons). These findings highlight the rapid, sustained efficacy of once daily oral upadacitinib in improving symptom burden and QoL in adults and adolescents with moderate-to-severe AD.

Background: Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit-risk profile for upadacitinib + topical corticosteroid (TCS) in patients with moderate-to-severe atopic dermatitis. Objective: We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks. Methods: Patients aged 12 to 75 years with chronic moderate-to-severe atopic dermatitis >= 10% of body surface area affected, Eczema Area and Severity Index [EASI] >= 16, Validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] >= 3, and Worst Pruritus Numerical Rating Scale[WP-NRS] score >= 4) were randomized 1:1:1 to once-daily upadacitinib 15 mg + TCS, upadacitinib 30 mg+TCS, or placebo (PBO) + TCS(rerandomized at week 16 to upadacitinib 1 TCS). Safety and efficacy, including proportion of patients experiencing >= 75% improvement in EASI (EASI-75), vIGA-AD of clear/almost clear with improvement >= 2 grades (vIGA-AD 0/1), and WP-NRS improvement >= 4, were assessed through week 52. Missing data were primarily handled by nonresponse imputation incorporating multiple imputation for missing values due to coronavirus disease 2019 (COVID-19). Results: Of 901 patients, 300 were randomized to upadacitinib 15 mg + TCS, 297 to upadacitinib 30 mg + TCS, and 304 to PBO + TCS. For all end points, efficacy for upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS at week 16 was maintained through week 52. At week 52, the proportions of patients treated with upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS who experienced EASI-75 were 50.8% and 69.0%, respectively; 33.5% and 45.2%, respectively, experienced vIGA-AD 0/1; and 45.3% and 57.5%, respectively, experienced WP-NRS improvement >= 4. Upadacitinib + TCS was well tolerated through 52 weeks; no new important safety risks beyond the current label were observed. No deaths were reported; major adverse cardiovascular events and venous thromboembolic events were infrequent (<= 0.2/100 patient-years). Conclusions: Results through 52 weeks demonstrate long-term maintenance of efficacy and a favorable safety profile of upadacitinib + TCS in patients with moderate-to-severe AD.

Background: Atopic dermatitis (AD) is severely burdensome, and there has been poor characterization of any differences in impact based on the area affected.Objective: To estimate the prevalence and HRQoL impact of head/face/neck/hand (HFNH) involvement among patients with moderate-to-severe atopic dermatitis.Methods: All TARGET-DERM AD registry patients with moderate/severe Investigator Global Assessment (vIGA-AD) were assessed using the Patient Oriented SCORing Atopic Dermatitis, Patient Oriented Eczema Measure (POEM) and the (Children's) Dermatology Life Quality Index ((C)DLQI).Results: 541 participants met the criteria (75.0% adults) and 84% (N = 453) reported HFNH involvement. HFNH and non-HFNH involved participants had similar characteristics; 55.2% female and 46.9% White. Compared to the non-HFNH involved, the involved had severe vIGA-AD (28.5% vs 16.3%, P = .02) and higher median body surface area affected (15% vs 10%, P # .01) and were twice as likely to have higher (C) DLQI and POEM scores.Limitations: This was an analysis of real-world and patient reported outcome data.Conclusion: Real-world HFNH involved AD patients were associated with significantly worse quality of life, POEM/(C)DLQI, and more severe disease. Detailed assessments of specific areas affected by AD are needed to personalize treatment.