Introduction & Objectives Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with comorbidities, including major adverse cardiovascular (CV) events (MACE), venous thromboembolism (VTE), and malignancy (excluding nonmelanoma skin cancer [exNMSC]). Incidence of MACE, VTE, and malignancy (exNMSC) was comparable to or lower than background rates reported in US AD population. We evaluated long-term incidence rates of MACE, VTE, and malignancy (exNMSC) by CV risk category among patients with AD with up to 6 years of UPA treatment. Materials & Methods Data were pooled from the phase 3, randomized, double-blind, multicenter, placebo-controlled Measure Up 1 & 2 (NCT03569293, NCT03607422) and AD Up (NCT03568318) trials. AD patients were randomized 1:1:1 to once-daily oral UPA 15 mg, UPA 30 mg, or placebo. After the 16-week double-blind treatment period, patients receiving UPA continued their assigned treatment, while patients treated with placebo were rerandomized 1:1 to UPA 15 mg or 30 mg. Incidence rates for MACE (CV death, nonfatal myocardial infarction, or nonfatal stroke), VTE (deep vein thrombosis or pulmonary embolism [fatal and nonfatal]), and malignancy (exNMSC) were evaluated as exposure-adjusted incidence rates per 100 patient-years (n/100 PY). MACE, VTE, and malignancy (exNMSC) background rates in the general US AD population were assessed in a retrospective observational claims-based analysis from Optum’s deidentified Clinformatics Data Mart database; this real-world reference population included patients with an AD diagnosis during the study period (March 2017–September 2024) determined by International Classification of Diseases 9th or 10th edition codes (≥ 1 inpatient or ≥ 2 outpatient claims for AD), and age restrictions from the UPA studies (12–75 years) were implemented. Background rates were weighted to mimic the age and sex distribution in the combined UPA trial population. Cohort stratification was based on the presence of CV risk factors at baseline (0 vs ≥ 1); UPA phase 3 data were further stratified by 1 vs 2 CV risk factors. CV risk factors included prior CV event, hypertension, diabetes mellitus, tobacco/nicotine use (current and former), elevated low-density lipoprotein cholesterol, or lowered high-density lipoprotein cholesterol. Results 2683 UPA-treated patients were included (UPA 15 mg, n = 1337, PY = 4435.2; UPA 30 mg, n = 1346, PY = 4752.5). MACE, VTE, and malignancy (exNMSC) background rates from the claims-based study were evaluated in 50,447 patients with AD. Long-term incidence rates in patients with up to 6 years of UPA treatment were low for MACE and VTE (all ≤ 0.2 n/100 PY) and malignancy (exNMSC; all ≤ 0.7 n/100 PY) and similar for patients who had 0 vs ≥ 1 CV risk factor. Rates from UPA phase 3 studies were similar to real-world US incidence rates in patients with AD. Rates remained low when UPA-treated patients were stratified by 1 vs 2 CV risk factors. Conclusion Incidence rates of MACE, VTE, and malignancy (exNMSC) in patients with moderate-to-severe AD who received up to 6 years of UPA treatment remained low and consistent with those observed in the overall population of patients with AD, regardless of CV risk category.

Abstract Atopic dermatitis (AD) management should be guided by disease activity. Continuous follow-up after initiating treatment is necessary to determine whether adequate disease control has been achieved. Recommended AD disease control targets include clinically meaningful changes in skin lesions, itch and quality of life (QoL), utilizing clinician- and patient-reported measures. This analysis assessed disease control as a composite of skin lesions, itch and QoL, in patients with AD treated with nemolizumab up to 2 years in the ARCADIA long-term extension (LTE; NCT03989206). This ARCADIA LTE post hoc analysis included adult patients who were either nemolizumab previously experienced (NPE) or nemolizumab naive (NN). Disease control was assessed (observed cases) at weeks 20, 56 and 104 and defined as achieving a composite of ≥ 75% reduction from lead-in baseline in Eczema Area and Severity Index (EASI 75), and a ≥ 4-point improvement from lead-in baseline in both itch visual analogue scale (VAS) and Dermatology Life Quality Index (DLQI). This study was funded by Galderma. As previously reported as individual endpoints, at week 104 (vs. lead-in baseline; observed cases), in NPE and NN patients, respectively, 88.2% and 85.4% achieved EASI 75, 87.2% and 82.0% achieved ≥ 4-point improvement in itch VAS, and 92.2% and 91.0% achieved ≥ 4-point improvement in DLQI. The proportion of NPE patients achieving the composite endpoint of disease control continued to increase over 2 years, being 44.5% (367 of 824) at week 20, 56.4% (384 of 681) at week 56 and 67.9% (340 of 501) at week 104. The proportion of NN patients achieving disease control showed a similar trend, being 40.6% (234 of 576) at week 20, 54.4% (253 of 465) at week 56 and 59.7% (187 of 313) at week 104. Long-term treatment with nemolizumab was associated with high levels of AD disease control, with continuous improvements up to 2 years. In both the NPE and NN arms, > 40% of patients achieved disease control by week 20, rising to approximately 60% by week 104.

Abstract APG777 is a first-in-class, half-life-extended, monoclonal antibody that blocks interleukin-13-mediated signalling. APG777 is being evaluated in moderate-to-severe AD with the goal of reducing injection burden. Primary efficacy and safety results are reported from the first 16 weeks of part A of the phase II APEX study (NCT06395948). APEX is a two-part, multicentre, randomized, placebo-controlled phase II trial. Part A consists of screening, 16-week induction and 36-week maintenance periods. Biologic-naive participants with moderate-to-severe AD were randomized 2 : 1 to APG777 or matched placebo. The primary endpoint was percentage change from baseline in Eczema Area and Severity Index (EASI) at week 16. Secondary endpoints included EASI 75 (≥ 75% improvement from baseline), EASI 90, Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) score of 0 or 1, and change in Individualized Numeric Rating Scale (I-NRS). Post hoc analyses were carried out to assess the relationship between APG777 exposure and efficacy. Treatment with APG777 resulted in a significant 71.0% reduction in EASI from baseline to Week 16 (vs. 33.8% placebo; P < 0.001). APG777 was well tolerated during the 16-week induction period, with greater reductions from baseline in EASI over placebo as early as week 2. Significantly greater percentages of participants in the APG777 group achieved EASI 75, EASI 90 and vIGA-AD 0/1 responses at week 16 compared with placebo, and significant improvement in I-NRS was observed as early as day 3. In post hoc analysis, higher exposures to APG777 led to greater reductions in EASI and higher EASI 75 responses. The most common adverse events (occurring in ≥ 5% of participants treated with APG777) included noninfective conjunctivitis and upper-respiratory-tract infection, occurring in 15% and 9% of participants in the APG777 group vs. 2% and 12% of participants in the placebo group, respectively. Most cases of noninfective conjunctivitis were mild or moderate and transient, and resolved by week 16. Treatment with APG777 led to significant improvement in the signs and symptoms of AD and was well tolerated. The primary results of this phase II trial support further evaluation of dosing every 12 weeks or every 24 weeks.

Introduction Lebrikizumab dosed every 4 weeks (LEBQ4W) in ADjoin demonstrated sustained response up to 3 years in patients with atopic dermatitis (AD) who were Week-16 responders. In ADvocate1/ADvocate2 during the maintenance period (Weeks 16-52), a high proportion of patients exhibited durable efficacy in the lebrikizumab withdrawal (placebo) arm, suggesting the possibility of less frequent dosing. We report results from a 32-week extension to ADjoin assessing efficacy and safety of LEBQ8W. Methods ADjoin is a 100-week long-term extension study assessing lebrikizumab 250 mg every 2 weeks (LEBQ2W) and every 4 weeks (LEBQ4W) in patients who completed qualifying parent studies. Qualifying patients from ADvocate1, ADvocate2, ADore, and ADopt-VA who completed ADjoin Week 100 were re-randomized to open-label LEBQ8W or LEBQ4W for a 32-week extension. Primary outcomes were percentages of patients achieving Investigator’s Global Assessment score of 0 or 1 (IGA 0/1) and ≥75% improvement in Eczema Area and Severity Index (EASI 75) at Week 32. Key secondary outcomes included percentage of patients achieving EASI 90 and change from baseline in the Patient-Oriented Eczema Measure (POEM). Safety data were collected throughout the extension. A combined non-responder imputation and multiple imputation method were used to address intercurrent events and missing data. The study was not powered to detect if LEBQ4W dosing is comparable to LEBQ8W dosing. Results 103 patients (LEBQ8W, N=51; LEBQ4W, N=52) enrolled in the 32-week extension (mean 60 days without lebrikizumab from ADjoin Week 100 to start of extension). Mean values for parent study baseline characteristics in LEBQ8W and LEBQ4W, respectively, were: AD disease duration, 17.1 and 17.7 years; EASI, 31.0 and 26.6; body surface area, 48.3% and 39.3%; and POEM, 20.9 and 19.8. Upon entering the extension, 64.7% and 73.1% of LEBQ8W and LEBQ4W patients, respectively, had achieved EASI 90, and mean (SD) POEM scores were 8.7 (7.6) and 6.0 (5.4), respectively. At Week 32 of the extension, percentages of patients (95% confidence interval) who achieved IGA 0/1 were 62.0% (48.3, 75.8) and 73.0% (60.9, 85.1) in LEBQ8W and LEBQ4W, respectively; 79.1% (67.6, 90.5) and 86.2% (76.8, 95.7) of patients achieved EASI 75 and 68.7% (55.8, 81.6) and 78.2% (66.8, 89.5) achieved EASI 90; POEM mean (SD) absolute scores (as observed) were 9.2 (7.3) in LEBQ8W and 5.4 (5.2) in LEBQ4W. All adverse events (AEs) were mild or moderate in severity. No serious AEs or AEs leading to discontinuation were reported; there was no evidence of increased risk of anti-drug antibodies with less frequent dosing. Conclusion Lebrikizumab dosed every 8 or 4 weeks provided long-lasting response in patients with moderate-to-severe AD, supporting its durable and potential disease-modifying effect in AD.

Introduction: We report efficacy and safety of lebrikizumab (LEB) in long-term extension study ADjoin (NCT04392154) following up to 152 Weeks (W) of continuous LEB treatment with/without TCS. Methods: Patients in ADvocate1&2 who achieved per-protocol response (EASI 75 or IGA 0/1 without rescue) following 16W of LEB treatment were re-randomized 2:2:1 to LEB250mg Q2W, LEB250mg Q4W, or placebo (LEB withdrawal). Patients who completed W52 of ADvocate1&2 could enroll in ADjoin. Patients who completed 16W of ADhere could enroll into ADjoin; per-protocol LEB responders were randomized 2:1 to LEB250mg Q2W or Q4W. Intermittent use of topicals was allowed in ADvocate1&2 W16–52, topicals and short-term systemics were allowed in ADjoin. Data are reported for W16 LEB responders originating from ADvocate1&2 (N=181) and ADhere (N=86) who received LEB250mg Q2W or Q4W in ADjoin. Efficacy outcomes were assessed based on all collected data (as observed analysis) up to W100 of ADjoin (total 152W and 116W of LEB treatment for patients from ADvocate1&2 and ADhere, respectively). Safety was reported from ADjoin enrollment up to the data cut-off April 24, 2024. Results: In patients from ADvocate1&2, at W152 IGA 0/1 was maintained by 82.9% (34/41; Q2W) and 84.0% (42/50; Q4W) and EASI 75 was maintained by 90.5% (57/63; Q2W) and 94.1% (64/68; Q4W) of patients. In patients from ADhere, at W116 IGA 0/1 was maintained by 86.7% (26/30; Q2W) and 91.7% (11/12; Q4W) and EASI 75 was maintained by 94.9% (37/39; Q2W) and 90.9% (20/22; Q4W) of patients. EASI 90 was reported by 79.4% (50/63; Q2W) and 86.8% (59/68; Q4W) of ADvocate1&2 patients at W152 and 84.6% (33/39; Q2W) and 86.4% (19/22; Q4W) of ADhere patients at W116. During 100Ws of ADjoin, most adverse events (AE) reported were mild (29.2%, 78/267) or moderate (33.3%, n=89) in severity. Serious AEs were reported by 4.1% (n=11) of patients. There was one death due to natural causes in the ADhere Q2W arm. AEs leading to treatment discontinuation were reported by 2.6% (n=7) of patients. Conclusion: Efficacy outcomes were maintained long-term, up to 3 years of continuous LEB treatment, in both LEB250mg Q2W and Q4W arms. The safety profile of LEB in ADjoin was consistent with previous LEB studies in patients with moderate-to-severe AD.