Investigator's Global Assessment Research Articles

Evaluation of the effectiveness of the combination of doxycycline and trifarotene for managing acne vulgaris of moderate to severe severity: a study in a tertiary care hospital

Background: Acne vulgaris (AV), affecting diverse skin types, prompts a uniform therapeutic approach, with options ranging from topical to systemic treatments. Trifarotene, a fourth-generation topical retinoid, offers precise skin-specific effects, especially in facial and truncal acne treatment. The study aimed to evaluate the effectiveness of the combination of doxycycline and trifarotene for managing AV of moderate to severe severity. Methods: At Mymensingh medical college hospital, the study enrolled 100 individuals to evaluate a new treatment for moderate AV from Jan-Jun 2023. Treatment comprised oral doxycycline (100 mg) and topical trifarotene (0.005% w/w) over 2 months, following a stratified randomization process. Evaluation criteria included clinical scores, lesion counts, and safety parameters, analyzed using SPSS v20. Results: Study on doxycycline and trifarotene for moderate to severe acne shows promising results. Participants, mainly aged 15-25 exhibit diverse demographics and balanced gender ratio. Significant improvement on investigator's global assessment (IGA) scale is noted, with 35% experiencing notable progress at 9-10 weeks, alongside reduction in Propionibacterium acnes growth and positive patient feedback with 36% reporting 'good' response. Conclusions: The study on doxycycline and trifarotene for moderate acne exhibits robust methodology with adherence to established practices and stratified randomization. Results, assessed via IGA, demonstrate promising efficacy and safety, providing insights for diverse skin types' acne management enhancement.

Topical ruxolitinib 1.5% (JAK1/JAK2 inhibitor) improves clinical and patient‐reported outcomes in moderate to severe chronic hand dermatitis: Data from a small open‐label trial

AbstractBackgroundChronic hand dermatitis (CHD) has suboptimal treatments and a negative impact on quality of life (QoL). Topical ruxolitinib, a JAK1/JAK2 inhibitor, is approved for vitiligo and mild‐to‐moderate atopic dermatitis, but has not previously been studied specifically for CHD.ObjectivesEvaluate the impact of ruxolitinib in CHD.MethodsA 12‐week, investigator‐initiated, open‐label trial evaluated ruxolitinib 1.5% in 15 adults with recalcitrant moderate‐to‐severe CHD. Primary outcomes included the proportion of patients: (1) achieving an Investigator Global Assessment (IGA) treatment success (0 or 1 score with a two‐step improvement) (2) a Hand Eczema Severity Index (HECSI)‐75 improvement at 12 weeks. Additional outcomes: clinical improvement at 4 and 8 weeks, improvement in itch (Numerical Rating Scale [NRS]) and QoL outcomes (i.e., Dermatology Life Quality Index [DLQI] and Skindex‐Mini).ResultsAt 12 weeks, 13/15 participants (86%) achieved a HECSI‐75, 12/15 participants (80%) had a two‐point reduction in IGA and 8/15 participants (53%) achieved an IGA treatment success. Both atopic dermatitis (AD; n = 7) and non‐AD (n = 8) CHD participants had clinical improvement in HECSI at 12 weeks (p < 0.01). 10/12 participants with baseline NRS ≥ 2 (83%) achieved a ≥ 2 point reduction on average itch at 12 weeks. 9/10 with baseline NRS ≥ 4 (90%) achieved a ≥4‐point itch reduction by 4 and 12 weeks. A significant decline in self‐reported daily itch (average and worst) was observed within the first week of treatment (p < 0.001). By CHD subtype, AD‐CHD had greater itch at baseline compared to non‐AD CHD (p < 0.01), consequently itch reduction was greater in AD‐subtype. Improvement in QoL (DLQI, Skindex‐Mini) was achieved at 4 weeks maintained to 12 weeks (p < 0.01). No treatment‐related adverse events were reported during the study and no rescue medications were used.ConclusionsRuxolitinib may be a promising treatment for CHD, improving clinical outcomes, itch and QoL. Significant improvement was achieved at 4 weeks and maintained through 12 weeks of treatment.

Efficacy and safety of Ruxolitinib, Crisaborole, and Tapinarof for mild-to-moderate atopic dermatitis: a Bayesian network analysis of RCTs.

Given the lack of head-to-head studies of novel non-steroidal molecule topical therapies in mild-to-moderate atopic dermatitis (AD), network meta-analyses (NMAs) can provide comparative efficacy and safety data for clinical decision-making. In this NMA, we performed a literature search until 01 March 2023 for eligible studies written in English using databases, including PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov. Only double-blind randomized clinical trials (RCTs) with topical Ruxolitinib, Crisaborole, or Tapinarof versus vehicle for patients with mild-to-moderate AD were included. Baseline and follow-up data were extracted. Efficacy was evaluated using Investigator's Global Assessment (IGA) achieving "clear" or "almost clear," with 2 points or more improvement from baseline at the end of treatment, referred to as "IGA success." For binary outcomes, we analyzed in random-effects Bayesian NMA consistency models to compare the efficacy of these 3 topical therapies by odds ratio (OR) with 95% credibility interval (CrI). Overall, 10 phase 2 or phase 3 RCTs were identified, which included 4010 patients with mild to moderate AD. Compared with the topical vehicle control, all these 3 treatments had higher response rate of "IGA success" at the end of trial (Ruxolitinib 1.5% b.i.d: OR, 11.94; 95%CrI, 6.28-23.15; Crisaborole 2% b.i.d: OR, 2.08; 95%CrI, 1.46-3.52; Tapinarof 1% b.i.d: OR, 2.64; 95%CrI, 0.75-9.70). Notably, Ruxolitinib 1.5% b.i.d. had the highest probability of achieving "IGA success" in ranking analysis (Rank 1, SUCRA = 0.75) and lower risk of AE (Rank 8, SUCRA = 0.22). Besides, there was no difference in treatment-related adverse events between 3 therapies. Heterogeneity was not significant across studies.

Comparison of the Efficacy of Tazarotene 0.045% versus Halobetasol Propionate 0.01% Lotion for the Treatment of Scalp Psoriasis at Tertiary Care Hospital, Karachi

Background: Psoriasis is a chronic, genetically determined inflammatory skin condition characterized by erythematous plaques with silvery scales, affecting about 2% of the global population. It significantly impacts patients' quality of life, encompassing physical, emotional, and psychosocial dimensions. While the use of topical corticosteroids (TCS) with tazarotene has shown benefits in plaque psoriasis treatment, limited data are available on the efficacy of combining halobetasol and tazarotene. Objective: This study aimed to compare the efficacy of Tazarotene 0.045% cream (TAZ) versus Halobetasol Propionate 0.01% lotion (HP) for the treatment of scalp psoriasis at a tertiary care hospital in Karachi, providing insight into their comparative effectiveness and informing clinical decision-making. Methods: A randomized control trial was conducted at the Dermatology Department of Jinnah Postgraduate Medical Centre, Karachi, from August 2022 to February 2023. Ninety participants with scalp psoriasis were recruited and randomly assigned to two groups: Group A (n=45) received Tazarotene 0.045% cream, and Group B (n=45) received Halobetasol Propionate 0.01% lotion, both applied once daily for 6 weeks. The primary outcome was the change in Investigator's Global Assessment (IGA) score from baseline to week 6. Data analysis was performed using SPSS version 25, focusing on descriptive statistics and inferential analyses to evaluate treatment efficacy. Results: The study observed a significant reduction in IGA scores from baseline in both groups, with Group A (TAZ) showing a decrease from 3.89 ± 0.68 to 1.29 ± 0.62 and Group B (HP) from 3.87 ± 0.66 to 2.49 ± 0.62. The paired difference in IGA scores indicated a more pronounced improvement in the TAZ group (2.60 ± 0.75) compared to the HP group (1.37 ± 0.57), with significant differences between the groups (p<0.0001). Treatment success was observed in 82.2% of participants in the TAZ group compared to 51.1% in the HP group, with an odds ratio of 4.424 (95% CI: 1.690—11.578; p=0.002). Conclusion: Tazarotene 0.045% cream demonstrates significantly greater efficacy in treating scalp psoriasis compared to Halobetasol Propionate 0.01% lotion. The findings suggest Tazarotene as a preferable treatment option for scalp psoriasis, offering a better therapeutic outcome.

Efficacy and safety of crisaborole ointment, 2%, in participants aged ≥45 years with stasis dermatitis: Results from a fully decentralized, randomized, proof-of-concept phase 2a study

Crisaborole ointment, 2%, is a nonsteroidal topical phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis. To evaluate the efficacy and safety of crisaborole in stasis dermatitis (SD). In this randomized, double-blind, vehicle-controlled, decentralized phase 2a study (NCT04091087), 65 participants aged ≥45years with SD without active ulceration received crisaborole or vehicle (1:1) twice-daily for 6weeks. The primary end point was percentage change from baseline in total sign score at week 6 based on in-person assessment. Crisaborole-treated participants had significantly reduced total sign score from baseline versus vehicle based on in-person (nondermatologist) assessment (-32.4% vs -18.1%, P=.0299) and central reader (dermatologists) assessment of photographs (-52.5% vs -10.3%, P=.0004). Efficacy according to success and improvement per Investigator's Global Assessment score and lesional percentage body surface area reached statistical significance based on central reader but not in-person assessments. Skin and subcutaneous tissue disorders were common all-causality treatment-emergent adverse events with crisaborole. Small sample size and short treatment duration were key limitations. In-person assessment was not conducted by dermatologists. Crisaborole improved signs and symptoms of SD and was well tolerated. Central reader assessment represents a promising approach for siteless clinical research.

542 - Validation of the skin pain numerical rating scale of the Pruritus and Symptoms Assessment for Atopic Dermatitis for adults and adolescents with moderate-to-severe atopic dermatitis

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

516 - Comparative efficacy of targeted systemic therapies with topical corticosteroids for moderate-to-severe atopic dermatitis: an updated network meta-analysis

Abstract Introduction Network meta-analysis (NMA) provides useful information for medical decision makers via comprehensive indirect comparisons across therapies. As the targeted systemic therapy options for moderate-to-severe atopic dermatitis (AD) continue to grow, it is critical to update NMAs as well. Objectives To assess the comparative efficacy of targeted systemic therapies with concomitant topical corticosteroids (TCS) in moderate-to-severe AD by including the latest Phase 3 combination therapy data for abrocitinib, lebrikizumab, and dupilumab in the NMA presented in Thyssen et al, 2021.1 Methods Data from the Phase 3 combination therapy trial for lebrikizumab in moderate-to-severe AD (ADhere [NCT04250337]) as well as an additional abrocitinib-dupilumab head-to-head Phase 3 trial (JADE DARE [NCT04345367]) were included in the analyses along with other eligible trials for abrocitinib, baricitinib, dupilumab, tralokinumab, and upadacitinib identified through a systematic literature review in Thyssen et al., 2021. Outcomes included ≥90% and ≥75% improvement in Eczema Area and Severity Index (EASI 90, EASI 75) from baseline, ≥4-point improvement in Pruritus Numerical Rating Scale from baseline (ΔNRS ≥4), and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with a ≥2-point reduction from baseline (IGA 0/1), at the week 16 timepoint of each study. Bayesian NMA was performed with fixed and random effects models, with and without baseline risk-adjustment; fit statistics were assessed. Inconsistency was assessed via unrelated mean relative effects models. Odds ratio (OR), number needed to treat (NNT), placebo-unadjusted absolute response rate (ARR), and Surface Under the Cumulative RAnking curve (SUCRA) scores were estimated. Statistical significance was assessed by OR 95% credible intervals excluding 1. Results The updated NMA analyzed 8 unique placebo-controlled trials and 1 active-controlled trial involving 4391 patients in 23 arms across 6 targeted therapies. Fit statistics supported fixed effects models across outcomes. All therapies were statistically more efficacious than placebo across all outcomes except baricitinib 2 mg for EASI-90. For EASI-90, upadacitinib 30 mg had the most favorable response estimates (ARR=63.2%, OR=11.3, NNT=2.0, SUCRA=98.3%), followed by abrocitinib 200 mg (ARR=55.8%, OR=8.3, NNT=2.4, SUCRA=90.0%), dupilumab 300 mg (ARR=44.8%, OR=5.3, NNT=3.2, SUCRA=68.3%), abrocitinib 100 mg (ARR=44.0%, OR=5.2, NNT=3.3, SUCRA=65.8%), upadacitinib 15 mg (ARR=42.9%, OR=4.9, NNT=3.4, SUCRA=64.3%), and the newly added lebrikizumab 250 mg (ARR=28.9%, OR=2.7, NNT=6.6, SUCRA=39.9%). The rank order for EASI-75 was similar (upadacitinib 30 mg [ARR=78.3%, OR=9.5, NNT=2.0, SUCRA=98.5%], abrocitinib 200 mg [ARR=73.0%,OR=7.1, NNT=2.3, SUCRA=89.1%], upadacitinib 15 mg [ARR=66.1%, OR=5.1, NNT=2.7, SUCRA=71.0%], dupilumab 300 mg [ARR=65.3%, OR=5.0, NNT=2.7, SUCRA=69.2%], abrocitinib 100 mg [ARR=60.3%, OR=4.0, NNT=3.2, SUCRA=54.0%], and lebrikizumab 250 mg [ARR=54.5%, OR=3.1, NNT=3.8, SUCRA=41.2%]). For ΔNRS ≥4, upadacitinib 30 mg had the most favorable response (ARR=68.9%, OR=10.0, NNT=2.1, SUCRA=99.9%), followed by upadacitinib 15 mg (ARR=56.6%, OR=5.9, NNT=2.7, SUCRA=84.0%), abrocitinib 200 mg (ARR=51.6%, OR=4.8, NNT=3.1, SUCRA=75.6%), dupilumab 300 mg (ARR=49.3%, OR=4.4, NNT=3.3, SUCRA=67.0%), baricitinib 4 mg (ARR=44.4%, OR=3.6, NNT=4.0, SUCRA=57.7%), and abrocitinib 100 mg (ARR=35.9%, OR=2.5, NNT=5.9, SUCRA=36.1%); lebrikizumab 250 mg ranked eighth (ARR=33.4%, OR=2.3, NNT=7.0, SUCRA=31.3%). For IGA 0/1, upadacitinib 30 mg (ARR=66.5%,OR=11.7, NNT=2.0, SUCRA=99.6%) had the most favorable estimates, followed by abrocitinib 200 mg (ARR=53.5%, OR=6.8, NNT=2.6, SUCRA=86.6%), upadacitinib 15 mg (ARR=48.0%, OR=5.4, NNT=3.0, SUCRA=76.2%), dupilumab 300 mg (ARR=42.1%, OR=4.3, NNT=3.7, SUCRA=64.7%), abrocitinib 100 mg (ARR=39.1%, OR=3.8, NNT=4.1, SUCRA=56.1%), and baricitinib 4 mg (ARR=30.6%, OR=2.6, NNT=6.4, SUCRA=39.9%); lebrikizumab 250 mg ranked seventh (ARR=29.2%, OR=2.4, NNT=7.0, SUCRA=35.8%). Baricitinib 2 mg and tralokinumab 300 mg were generally ranked lower across outcomes. Conclusions Among targeted therapies for moderate-to-severe AD used with concomitant TCS for 16 weeks, upadacitinib 30 mg remained the most efficacious therapy in this NMA, generally followed by abrocitinib 200 mg, upadacitinib 15 mg or dupilumab 300 mg, abrocitinib 100 mg, and baricitinib 4 mg or lebrikizumab 250 mg.

493 - Lebrikizumab does not impact vaccine-induced immune responses: results from a phase 3 study in adult patients with moderate-to-severe atopic dermatitis

Abstract Introduction Lebrikizumab (LEB) is a monoclonal antibody (Ab) that has shown efficacy and safety in patients with moderate-to-severe atopic dermatitis (AD) in Phase 2/3 trials. LEB targets IL-13 and inhibits signaling of the IL-4Rα/IL-13Rα1 complex. The potential immunomodulator effect of LEB necessitates investigating its impact on immune responses. Objectives To report the seroresponses to the Tdap (Diphtheria/Tetanus Toxoids/Pertussis) and MCV (Meningococcal (Groups A, C, Y, and W-135)) vaccines in LEB-treated and placebo (PBO)-treated adult patients (aged 18-15 years) with moderate-to-severe AD; and to compare the efficacy of LEB vs PBO in the treatment of AD. Methods ADopt-VA was a US Phase 3, 16-week (W) randomized, double-blind, placebo-controlled study to assess LEB impact on vaccine immune responses in adult patients with moderate-to-severe AD. The primary endpoint was the immune response to 2 vaccines, the Tdap and MCV . LEB was given as a 500 mg loading dose at baseline and W2, followed by 250 mg LEB Q2W. At W12, both vaccines (Tdap and MCV) were administered to all patients, LEB group N=107, Placebo (PBO) group N=81. Immune responses were determined by Ab level differences between W12 and W16. Secondary efficacy endpoints at W16 were Investigator Global Assessment (IGA) and Eczema Area and Severity Index (EASI 75) scores. Results For Tdap, 73.6% of LEB patients had a positive Ab response vs 73.4% for PBO, 90% CI, 0.3 (-10.2, 11.2). For MCV, LEB patients had an 86.9% positive Ab response vs 75.0% for PBO, 90% CI, 12.2 (2.5, 22.0). IGA (0,1) was achieved by 40.6% of LEB patients vs 18.9% receiving PBO (p=<0.001); EASI 75 was achieved by 58.0% and 32.7% (p<0.001), respectively. The safety profile was consistent with previous LEB trials. Conclusions These data show that LEB does not negatively impact immune responses for Tdap or MCV vaccines in adults with moderate-to-severe AD.

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.

556 - A global, observational, cohort study of patients with atopic dermatitis to evaluate tralokinumab real-world clinical use (TRACE): baseline characteristics from the first 100 patients in Germany

Abstract Introduction/Background Tralokinumab is a high-affinity, fully human IgG4 monoclonal antibody that specifically targets interleukin-13, a key driver of atopic dermatitis (AD) disease progression. Clinical trials have shown that tralokinumab is efficacious in patients with moderate-to-severe AD and has a favorable safety profile, including a low frequency of adverse events such as conjunctivitis. Management of patients in routine clinical practice differs from those enrolled in clinical trials due to strict protocol criteria, and there is a lack of clinical data on tralokinumab use in the real-world setting. Objectives TRACE is a real-world study in patients with AD, aiming to better understand the effectiveness, safety, and clinical use of tralokinumab in daily practice. Here, we describe baseline characteristics from the first patients enrolled into TRACE in Germany. Methods TRACE is an observational, prospective, single-cohort study of adult patients with moderate-to-severe AD who are treated with tralokinumab, according to national approved labels. Eleven countries are participating in the study across Europe, North America and the Middle East. The primary objective is to assess changes in clinical signs and symptoms of AD in tralokinumab-treated patients. Secondary objectives are to investigate safety, quality of life, patient-reported outcomes and treatment adherence, among others. Results Of the first 100 patients initiated on tralokinumab, the mean age (standard deviation [SD]) was 44.7 years (17.9) and 58% were male. Most patients had moderate-to-severe AD with a mean Investigator’s Global Assessment (IGA) score of 3.5 (SD 0.7) and mean Eczema Area and Severity Index (EASI) of 22.5 (SD 12.9). Patients reported heavy symptomatic burden of disease; the mean eczema-related sleep numerical rating scale (NRS) was 5.6 (SD 2.9) and mean worst daily pruritus NRS was 6.2 (SD 2.7). Patients also reported a substantial impact on quality of life, demonstrated by a mean Dermatology Life Quality Index of 15.6 (SD 6.9). Overall, 79 patients were biologic-naïve and 19 were biologic-experienced (data missing; n=2). All biologic-experienced patients were previously treated with dupilumab, of whom most experienced one or more treatment failures. Reasons for switching from dupilumab included lack or loss of effectiveness, and adverse events, which most commonly included conjunctivitis. Conclusions Initial findings showed that most adult patients with moderate-to-severe AD who were treated with tralokinumab were biologic-naïve, indicating tralokinumab is prescribed as first-line systemic treatment in real-world clinical practice, in line with European Dermatology Forum guidelines. The main reasons for switching from dupilumab were lack or loss of effectiveness, and adverse events, such as conjunctivitis, indicating the need for alternative biologic treatments such as tralokinumab.

522 - Efficacy and safety of abrocitinib in combination with topical therapy in adolescents from China with moderate-to-severe atopic dermatitis: A post hoc analysis of the JADE TEEN phase 3 trial

Abstract Background Atopic dermatitis (AD) has a reported prevalence of 3% in adolescents aged 13-14 years in China. However, studies evaluating the efficacy and safety of Janus kinase 1-selective inhibitors in AD in patients from China are limited. Abrocitinib is an oral, once-daily, Janus kinase 1–selective inhibitor approved for the treatment of moderate-to-severe AD in adults and adolescents in the United States and in adults in China. The efficacy of abrocitinib as monotherapy or in combination with medicated topical therapy has been demonstrated in multiple phase 3 clinical trials in adolescent and adult patients with moderate-to-severe AD. In a separate phase 3 trial of adolescent patients (JADE TEEN [NCT03796676]), abrocitinib administered in combination with medicated topical therapy was effective in improving the signs and symptoms of moderate-to-severe AD, with an acceptable safety profile. JADE TEEN was conducted in several countries, including China. Objective To assess the efficacy and safety of abrocitinib in combination with topical therapy in Chinese adolescents with moderate-to-severe AD enrolled in JADE TEEN. Methods In JADE TEEN, adolescent patients (aged 12 to 17 years) were randomly assigned (1:1:1) to receive abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks in combination with medicated topical therapy. This post hoc analysis included data from patients enrolled in JADE TEEN from mainland China. Assessments included the proportion of patients at week 12 who achieved an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement from baseline, ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75), and ≥4 point improvement from baseline in Peak Pruritus Numerical Rating Scale (PP-NRS4; used with permission from Regeneron Pharmaceuticals, Inc., and Sanofi). Change from baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) total score at week 12 was also assessed. Safety was assessed by treatment emergent adverse event (TEAE) monitoring. Results Of 285 patients enrolled in JADE TEEN, 52 (18.2%) were enrolled from mainland China and consisted of 14, 18, and 20 patients who were randomly assigned to receive abrocitinib 200 mg, abrocitinib 100 mg, and placebo, respectively. Median age at baseline was 15.0 years (interquartile range [IQR], 14.0-17.0 years), and median duration since onset of AD was 9.8 (IQR, 4.4-13.7) years. At week 12, a higher proportion of patients treated with abrocitinib at either dose compared with placebo achieved efficacy responses of IGA 0/1 (abrocitinib 200 mg, 46.2%; abrocitinib 100 mg, 46.7%; placebo, 22.2%), EASI-75 (69.2%; 73.3%; 27.8%), and PP-NRS4 (63.6%; 50.0%; 20.0%). Decreases from baseline in PSAAD total score were greater in patients treated with abrocitinib at either dose compared to placebo at week 12 (abrocitinib 200 mg, −3.4; abrocitinib 100 mg, −3.2; placebo, −1.8). Response rates were largely comparable between patients from China and the overall JADE TEEN study population, although CIs were wider in the China subgroup because of the small sample size. In the China subgroup, TEAEs were experienced by 13 (92.9%), 16 (88.9%), and 15 (75.0%) patients in the abrocitinib 200 mg, abrocitinib 100 mg, and placebo groups, respectively. Compared to the overall population, there were no new safety signals identified in patients from China. Conclusions Abrocitinib administered in combination with medicated topical therapy was effective and well tolerated in adolescent patients from China with moderate-to-severe AD. Efficacy and safety findings were consistent with the overall JADE TEEN population.

484 - Phase 2 trial in progress - lirentelimab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments

Abstract Background Atopic dermatitis (AD) is a chronic pruritic inflammatory dermatitis that affects approximately 16.5 million (7.3%) adults in the US, of which around 6.6 million (40%) have moderate-to-severe disease. The current standard of care includes topical treatments supplemented with corticosteroids with and without immunosuppressants. Patients with AD inadequately controlled by topical treatments and immunosuppressants are often treated with biologics and/or JAK inhibitors. Some patients do not have an adequate clinical response or are unable to tolerate these treatments prompting the need for novel therapies. Study Rationale Mast cells (MCs) and eosinophils (eos) are implicated in the pathogenesis of AD. Sialic acid-binding Ig-like lectin (Siglec)-8 is expressed selectively on MCs and eos; engagement with an antibody results in broad inhibition of MC activation and eos depletion. Lirentelimab (AK002) is a humanized, nonfucosylated IgG1 monoclonal antibody that binds specifically to Siglec-8. Preclinical data demonstrates that lirentelimab can broadly inhibit multiple modes of mast cell stimulation that drive AD pathogenesis. Lirentelimab, administered every 4 weeks as an infusion (IV), has been tested in over 600 healthy volunteers and patients with inflammatory and allergic diseases; in those with concomitant AD, improvements in AD were observed. Overall, lirentelimab IV has been well-tolerated; the most common AE being infusion related reactions (IRRs) typically associated with the initial infusions. In a phase 1 study, a subcutaneous (SC) formulation of lirentelimab was well-tolerated with no IRRs. The results of these studies provide a strong rationale for conducting this phase 2 proof-of-concept, randomized, double-blind, placebo-controlled study of lirentelimab SC in adults with moderate–severe atopic dermatitis inadequately controlled by topical treatments (NCT05155085, “ATLAS”). Key Inclusion/Criteria Adults (18-80 years) are eligible for screening if they have had chronic AD presented for ≥3 years with moderate-to-severe symptoms defined as: Eczema Area and Severity Index (EASI) score ≥16, involvement of ≥10% of the Body Surface Area (BSA), and Investigator Global Assessment (IGA) score ≥3, documented recent history of inadequate response to treatment with medications such as topical corticosteroids, calcineurin inhibitors, JAK inhibitors, or PDE4 inhibitors (crisaborole), and biologic-naïve or biologic-exposed (secondary loss of response, intolerance, or lack of access). The complete list of inclusion/exclusion criteria will be presented. Study Design 130 patients will be randomized 1:1 to receive either 7 SC injections of 300mg lirentelimab or placebo every two weeks and then followed for 12 weeks after the last dose. The primary endpoint is the proportion of patients who achieve EASI-75 at week 14 (2 weeks after last dose) compared with baseline. All patients who receive study medication will be included in the safety analysis. Secondary endpoints include percent change in EASI at week 14 from baseline and proportion of patients with IGA of 0 or 1 and a 2-point improvement at week 14 compared to baseline. Patients who complete the study (day 99 visit of double-blind period) will be given the option to enroll in an open-label extension (OLE) for 7 doses of 300mg lirentelimab SC for 12 weeks. Qualified participants will receive medication, lab tests and medical care related to the study at no cost. Study Sites This study is currently enrolling in the USA and Germany. Please visit clinicaltrials.gov (NCT05155085) or email atlas.info@allakos.com to learn more about this study.

514 - Tapinarof cream 1% once daily: significant efficacy in the treatment of atopic dermatitis in two pivotal phase 3 trials in adults and children down to 2 years of age

Abstract Introduction Tapinarof cream 1% once daily (QD) demonstrated efficacy versus vehicle and was well tolerated in adults and adolescents with moderate to severe atopic dermatitis (AD) in a previously reported phase 2 trial. Objective Here, we report pivotal phase 3 efficacy and safety results for tapinarof cream 1% QD in the treatment of adults and children down to 2 years of age with AD. Materials and Methods ADORING 1 and 2 were two identical phase 3, randomized, double-blind, vehicle-controlled trials. Eligibility criteria included a Validated Investigator Global Assessment for Atopic DermatitisTM (vIGA-ADTM) score of ≥3, Eczema Area and Severity Index (EASI) score of ≥6, and body surface area (BSA) involvement of 5–35%. Patients were randomized 2:1 to receive tapinarof cream 1% or vehicle cream QD for 8 weeks. The primary efficacy endpoint was vIGA-ADTM response, defined as a score of clear (0) or almost clear (1) and ≥2-grade improvement from baseline at Week 8. Secondary efficacy endpoints included ≥75% improvement in EASI score (EASI75) and proportion of patients (aged ≥12 years) with a baseline Peak Pruritus-Numerical Rating Scale (PP-NRS) score of ≥4 who achieved a ≥4-point reduction at Week 8. Adverse events (AEs) included rates of AEs of special interest (AESIs): contact dermatitis, follicular event, and headache. Results 407 and 406 patients aged 2–81 years were randomized in ADORING 1 and 2, respectively. At baseline, 84.0–89.9% of patients had a vIGA-ADTM score of 3 (moderate), mean EASI score of 12.5–13.3, and mean BSA affected of 16.7–16.9% across trials. At Week 8, both the primary and all secondary efficacy endpoints were met with statistical significance in the tapinarof groups versus vehicle: vIGA-ADTM response rates were 45.4% vs 13.9% and 46.4% vs 18.0% (both P<0.0001); EASI75 response rates were 55.8% vs 22.9% and 59.1% vs 21.2% (both P<0.0001); and a ≥4-point reduction in PP-NRS was achieved by 55.8% vs 34.2% (P=0.0366) and 52.8% vs 24.1% (P=0.0015), in ADORING 1 and 2, respectively. AEs were mostly mild or moderate; the most frequent (≥5% in any group) were folliculitis, headache, and nasopharyngitis. Trial discontinuation rates due to AEs were lower with tapinarof versus vehicle (ADORING 1: 1.9% vs 3.6%; ADORING 2: 1.5% vs 3.0%, respectively). Rates of AESIs with tapinarof versus vehicle were: contact dermatitis 1.5% vs 2.2% and 1.1% vs 1.5%; follicular events 10.0% vs 0.7% and 8.9% vs 1.5%; and headache 7.0% vs 2.2% and 1.5% vs 0%, in each trial, respectively. Conclusions Tapinarof cream 1% QD demonstrated statistically significant efficacy compared with vehicle for primary and secondary efficacy endpoints in adults and children down to 2 years of age with AD. Tapinarof was well tolerated, with no new safety or tolerability signals. AEs were mostly mild to moderate and led to low rates of trial discontinuation, demonstrating the predictable safety profile of tapinarof cream 1% QD.

569 - 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

Abstract Background Therapeutic inertia, defined as the delay or reluctance in modifying treatment when goals are unmet, is a significant challenge in managing chronic diseases, including atopic dermatitis (AD). This inertia can lead to suboptimal control of the disease, affecting patient outcomes. Objectives This study aims to evaluate the effect of therapeutic inertia on patient-reported outcomes (PROs) in individuals with moderate-to-severe AD 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 outcomes at the initiation of systemic therapy and at subsequent 3-month intervals up to 12 months of follow-up. We assessed patient-reported outcomes (PROs) to determine the proportion of patients not meeting predefined treatment targets for PROs 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 predefined treatment targets based on expert consensus. 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.

498 - Real-world use and effectiveness of upadacitinib in adults and adolescents with atopic dermatitis: preliminary analysis of the real-world multicountry AD-VISE study

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

515 - Rapid and early onset of itch relief with tapinarof cream 1% once daily in two pivotal phase 3 trials in adults and children down to two years of age with atopic dermatitis

Abstract Introduction Itch is the most bothersome symptom for patients with atopic dermatitis (AD), with a significant negative impact on health-related quality of life. Rapid onset of pruritus relief with sustained efficacy is a key outcome for AD therapies. In a phase 2 trial in adults and adolescents with moderate to severe AD, tapinarof cream 1% once daily (QD) demonstrated efficacy versus vehicle and was well tolerated. Objective Here, we evaluate time to onset of itch relief in the pivotal phase 3 trials with tapinarof cream 1% QD in the treatment of adults and children down to 2 years of age with AD. Materials and Methods In ADORING 1 and 2, two identical, double-blind, vehicle-controlled trials, patients were randomized 2:1 to tapinarof cream 1% or vehicle QD for 8 weeks. Patients with a Validated Investigator Global Assessment for Atopic DermatitisTM score of ≥3, an Eczema Area and Severity Index score of ≥6, and body surface area involvement of 5–35% were included. Efficacy endpoints that evaluated itch relief were mean changes in Peak Pruritus-Numerical Rating Scale (PP-NRS) score (daily and by visit [Weeks 1, 2, 4, and 8]) from baseline through Week 8. The PP-NRS considers a person’s worst itch over the past 24 hours, assessed on an 11-point scale (0 indicates “no itch” and 10 is “worst imaginable itch”). Daily PP-NRS scores were recorded in diaries. Patients aged ≥12 years self-completed the PP-NRS, while caregivers completed it for children aged <12 years. Results 407 and 406 patients were randomized in ADORING 1 and 2. At baseline, mean (standard deviation [SD]) PP-NRS scores were 6.7 (2.4) and 6.8 (2.3) in both trials, respectively. For daily evaluations of itch from baseline, greater reductions in PP-NRS scores (mean [SD]) for tapinarof versus vehicle were observed as early as Day 1, 24 hours after initial application, in ADORING 1 (–1.2 [2.2] vs –0.9 [2.0]) and Day 2 in ADORING 2 (–1.6 [2.4] vs –1.4 [2.1]). Improvements in daily PP-NRS scores (mean [SD]) with tapinarof versus vehicle continued through the first 2 weeks (Day 14; –3.0 [2.8] vs –2.0 [2.4] and –2.9 [2.7] vs –1.8 [2.6]), and through Week 8 of both trials. There were statistically significant and clinically meaningful reductions in mean weekly PP-NRS scores as early as Week 1, the first assessment, for patients treated with tapinarof compared with vehicle (–2.0 vs –1.2 [P<0.0001]) and (–2.0 vs –1.3 [P=0.0010]), in ADORING 1 and 2, respectively. Significantly greater reductions in mean PP-NRS scores with tapinarof versus vehicle were seen for all visits through Week 8 (–4.1 vs –2.6 and –4.1 vs –2.4 [both P<0.0001]), for both trials. Conclusions Tapinarof cream 1% QD demonstrated rapid, clinically meaningful, and significant onset of pruritus relief as early as 24 hours after initial application compared with vehicle. Improvements in itch with tapinarof cream increased through Week 8 in both trials in adults and children down to 2 years with AD.

525 - Real-world effectiveness of upadacitinib in moderate-to-severe atopic dermatitis (AD): Results from cross-sectional analyses of the CorEvitas AD Registry

Abstract Introduction/Background Upadacitinib is an oral Janus kinase inhibitor approved to treat moderate-to-severe atopic dermatitis (AD). While clinical trials have demonstrated its efficacy in treating the signs and symptoms of AD, less is known about its effectiveness in a real-world setting. Objectives This cross-sectional study describes the real-world clinical and patient-reported outcomes of adults with AD enrolled in the CorEvitas AD Registry and treated with upadacitinib for at least four or more weeks. Methods The CorEvitas AD Registry is a prospective, non-interventional registry of adults diagnosed with AD by a dermatologist or qualified dermatology practitioner. The current analysis included participants enrolled between July 21, 2020 through August 7, 2023 who were treated with upadacitinib for at least 4 weeks at the time of evaluation by their provider. Outcome measures included assessments of: skin clearance (Validated Investigators Global Assessment Scale for Atopic Dermatitis [vIGA-AD™], Eczema Area and Severity Index [EASI]); worst itch in the past 24 hours (Peak Pruritus Numeric Rating Scale [PP-NRS]); symptom frequency (Patient-Oriented Eczema Measure [POEM]); quality of life (Dermatologic Life Quality Index [DLQI]); and disease control (Atopic Dermatitis Control Tool [ADCT]). Outcomes were cross-sectionally summarized using data collected at the latest registry visit (Overall cohort), as well as 1 to less than 5 months (1-5 months) and 5-9 months following upadacitinib initiation (Month 1-5 cohort and Month 5-9 cohort, respectively). Subgroup analyses were also conducted based on prior use of biologics indicated for AD (bio-naïve, bio-experienced). Data were analyzed as observed with no imputation. Safety events were not assessed in this ­analysis. Results A total of 335 patients (mean age 45.6 years; 51.6% female; 64.2% White) were treated with upadacitinib (15 mg: n=221 [70.8%]; 30 mg: n=91 [29.2%]; median treatment duration: 6.9 months). Some patients reported concomitant use of topical corticosteroids (28.1%) and prior use of biologics indicated for AD (dupilumab: 45.4%; tralokinumab: 6.0%). For the Overall cohort, 57.3% had clear or almost clear skin (vIGA-AD 0/1). An EASI ≤3 was observed in 74.8% of patients and 45.3% reported no/minimal itch (PP-NRS 0/1); 40.9% had both EASI ≤3 and PP-NRS 0/1. Most patients (69.3%) reported that their AD was controlled (ADCT <7), 36.4% reported clear or almost clear disease (POEM 0–2), and 39.8% reported no impact of AD on their quality of life (DLQI 0/1). Similar results were observed for the Month 1-5 (n=144) and Month 5-9 (n=194) cohorts; results in bio-naïve and bio-experienced patients were comparable. Conclusions More than half of patients with ≥4 weeks of upadacitinib treatment had clear or almost clear skin and greater than two-thirds reported controlled disease, with similar results observed in both bio-naïve and bio-experienced patients. Over a third reported no/minimal symptom and disease burden. These findings suggest that low levels of disease severity are observed with real-world use of upadacitinib. Future analyses will aim to report changes in disease severity and burden due to persistent upadacitinib treatment.

524 - Efficacy of upadacitinib and dupilumab on achieving stringent and composite skin and itch outcomes: an indirect comparison of adults with moderate-to-severe atopic dermatitis

Abstract Introduction/Background Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and Measure Up 2 assessed efficacy of upadacitinib 30mg and upadacitinib 15mg against placebo, while Heads Up assessed efficacy of upadacitinib 30mg in a head-to-head trial against dupilumab 300mg. Network meta-analysis has shown that upadacitinib 30mg and upadacitinib 15mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated stringent and composite measures of efficacy. Objectives To indirectly compare upadacitinib and dupilumab on stringent and composite measures of skin clearance and itch resolution. Methods A population-adjusted indirect comparison using covariate adjustment as a treatment effect calibration was conducted using individual patient data from Measure Up 1 and 2 and Heads Up. Specifically, the indirect comparison model estimated how upadacitinib 15 mg would have performed if included in Heads Up by adjusting for patient-level covariates (age, gender, race, country, previous use of systemic therapy, disease duration, baseline validated Investigator Global Assessment scale for AD score, and baseline Eczema Area and Severity Index [EASI]). Absolute response rates at weeks 4 and 16 were estimated for the following outcomes: no/minimal itch (Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1), 100% improvement in EASI (EASI 100), achievement of both ≥90% improvement in EASI (EASI 90) and WP-NRS 0/1, and achievement of both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to-treat population for the clinical trials, and utilized non-responder imputation. Results Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30 mg, followed by upadacitinib 15 mg, and then dupilumab. This pattern was observed at week 4 on the achievement of WP-NRS 0/1 (upadacitinib 30 mg: 34.2% | upadacitinib 15 mg: 18.2% | dupilumab: 7.9%), EASI 100 (8.5% | 4.7% | 1.8%), EASI 90 & WP-NRS 0/1 (21.9% | 10.6% | 3.3%), and EASI 100 & WP-NRS 0/1 (6.4% | 3.5% | 1.2%). This ranking was maintained at week 16 for WP-NRS 0/1 (35.4% | 22.5% | 16.2%), EASI 100 (28.4% | 22.2% | 7.9%), EASI 90 & WP-NRS 0/1 (32.2% | 19.6% | 12.4%), and EASI 100 & WP-NRS 0/1 (19.6% | 12.7% | 4.2%). Conclusions For adults with moderate-to-severe AD, upadacitinib 30 mg appears to be the most efficacious treatment in attaining stringent and composite outcomes after 4 and 16 weeks, followed by upadacitinib 15 mg, and then dupilumab.

568 - Persistent inadequate disease control and therapeutic inertia in moderate-to-severe atopic dermatitis: a 12-month longitudinal analysis of real-world outcomes from TARGET-DERM registry

Abstract Background Therapeutic inertia refers to the delay or failure to escalate treatment in patients who are not achieving adequate disease control and poses a challenge in the management of moderate-to-severe atopic dermatitis (AD). Despite the availability of conventional (CST) and advanced systemic therapies (AST) currently 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 aims to evaluate the occurrence therapeutic inertia (assessed as non-escalation of therapy despite limited disease control) and the proportion of patients with moderate-to-severe AD who continue to show an inadequate response after receiving systemic therapies for a duration ranging 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 pre-defined 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 a significant portion of moderate-to-severe AD patients fail to achieve adequate disease control with systemic therapies over 12 months, indicating a substantial presence of therapeutic inertia. These findings suggest a need for more proactive management strategies in AD treatment.

528 - Rapid skin clearance and itch improvement with upadacitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: results from a phase 3b head-to-head clinical trial (Heads Up)

Abstract Introduction/Background Atopic dermatitis (AD) is a chronic, recurrent, inflammatory disease characterized by multiple skin manifestations and intense itching that can impact patient quality of life. The effect of upadacitinib (UPA) and dupilumab (DUP) was evaluated in a double-blind, double-dummy, head-to-head phase 3b clinical trial (Heads Up; NCT03738397) of adult patients (age: 18-75 years) with moderate-to-severe AD (Eczema Area and Severity Index [EASI] ≥16; body surface area ≥10%; validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) ≥3 at screening and baseline; Worst Pruritus Numerical Rating Scale [WP-NRS] ≥4 at baseline) randomized 1:1 to UPA 30 mg orally once-daily (N=348) or DUP 300 mg subcutaneous injection every two weeks after a 600 mg loading dose (N=344). Objective The effects of UPA and DUP on skin clearance and itch improvement are reported here. Methods Skin clearance was assessed by EASI, with response defined as an improvement ≥75% (EASI75), ≥90% (EASI90), and 100% (EASI100) from baseline. Itch intensity was assessed daily by WP-NRS up to week 16, then at study visits up to week 24. Weekly WP-NRS scores were analyzed as a 7-day rolling average up to week 16, then at study visits through week 24. Daily WP-NRS scores were analyzed day-to-day through day 28. Mean percent improvement and the proportion of patients achieving clinically meaningful improvement (≥4-point improvement from baseline) were evaluated. The proportion of patients achieving a state of no/minimal itch (defined as WP-NRS score of 0/1) was evaluated as a post-hoc analysis. Results EASI75/90/100 response rates were significantly greater with UPA versus DUP at week 16 (UPA = 72.4%/61.6%/28.4%, DUP = 62.6%/40.3%/7.9%; P<0.01 for all comparisons), with greater EASI75 and EASI90 rates observed with UPA as early as week 1 (nominal P<0.05). Mean percent improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 67.8%, DUP= 49.6%; P<0.001), with greater improvement observed as early as week 1 (nominal P<0.001). Daily WP-NRS data showed a greater mean percent improvement with UPA versus DUP as early as day 2, the day after the first dose (UPA = 22.0%, DUP = 4.2%; nominal P<0.001). The proportion of patients that achieved clinically meaningful improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 56.1%, DUP = 36.4%; P<0.001), with greater proportions observed as early as week 1 (nominal P<0.001). Daily WP-NRS data showed a greater proportion of patients achieved clinically meaningful improvement with UPA versus DUP as early as day 2 (UPA = 15.3%, DUP = 3.4%; nominal P<0.001). The proportion of patients that achieved a state of no/minimal itch based on weekly WP-NRS was greater with UPA versus DUP at week 16 (UPA = 35.5%, DUP = 16.2%; nominal P<0.001) and at week 1 (nominal P<0.001). Conclusions Skin clearance and itch improvement were consistently better with UPA compared with DUP in adult patients with moderate-to-severe AD, with greater improvements observed as early as week 1 for skin clearance and the day following treatment for itch improvement.