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Introduction Lebrikizumab is an interleukin (IL)-13 inhibitor that has completed phase 3 studies. It demonstrated statistical superiority vs. placebo in patients with moderate-to-severe atopic dermatitis (AD) across all primary and key secondary endpoints at week 4 and week 16 of ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Objectives: The objective of this analysis is to determine lebrikizumab's impact on AD-relevant serum biomarkers in patients from these studies through week 16. Methods: Protein biomarkers were determined in available serum samples from patients receiving lebrikizumab 250 mg every 2 weeks (n=72) or placebo (n=36) from both ADvocate1 and ADvocate2. Pre- and post-treatment biomarkers were compared to healthy controls (HC, n=30) which were age, sex, race, and ethnically matched. The analysis included biomarkers known to be elevated in AD. IL-13 was only measured at baseline because of lebrikizumab's known interference with IL-13 measurement. Results: At baseline, CCL13, CCL17, CCL22, total IgE, IL-5, IL-13, and periostin were elevated in patients with AD (p<0.001) with IL-13 measuring approximately 7-fold greater in the AD population vs. HC. In patients with AD, IL-4, CCL11, CXCL10, CCL2, and CCL4 were not elevated at baseline vs. HC.At week 4, lebrikizumab significantly reduced levels of the key type 2 biomarkers, CCL13, CCL17, and periostin vs. placebo (p<0.01) with a trend toward levels consistent with HC (within 1.5-fold). At week 16, CCL13, CCL17, and periostin levels remained consistent with HC levels with CCL13 and periostin retaining statistically significant reductions vs. placebo (p<0.01). Conclusions: In sum, selective targeting of IL-13 with lebrikizumab monotherapy reduced known molecular biomarkers of systemic type 2 inflammation in patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Introduction Lebrikizumab is a novel monoclonal antibody that binds with high affinity and slow off-rate to IL-13, thereby blocking the downstream effects of IL-13 with high potency. The efficacy and safety of lebrikizumab have been investigated in a number of Phase 3 trials including: ADvocate1 (NCT04146363), ADvocate2 (NCT04178967), ADhere (NCT04250337), and ADjoin (NCT04392154). Lebrikizumab (with or without TCS) was efficacious in providing clinically meaningful improvements in the signs and symptoms of AD through Week(W) 52 in adult and adolescent patients with moderate-to-severe AD. Objectives: We report the efficacy and safety of lebrikizumab (LEB) in the long-term extension study ADjoin (NCT04392154) following 104 weeks of continuous LEB treatment with and without TCS use. Methods: Patients in ADvocate1&2 who achieved either EASI 75 or IGA 0/1 (without rescue) at W16 were re-randomized 2:2:1 to LEB250mg Q2W, LEB250mg Q4W, or placebo (LEB withdrawal). Patients who completed W52 of ADvocate1&2 were able to enroll in ADjoin. Patients in ADhere who achieved either EASI 75 or IGA 0/1 (without rescue) at W16 were able to enroll into ADjoin and randomized 2:1 to LEB250mg Q2W or LEB250mg Q4W. Data are reported for patients originating from ADvocate1&2 and ADhere who received LEB250mg Q2W or Q4W in ADjoin. Efficacy outcomes were assessed based on all collected data (as observed analysis) up to 104W of LEB treatment. Safety was reported from ADjoin enrollment up to the data cut-off April 14, 2023. Results: At W104, IGA 0/1 was maintained by 38/44 (86.4%; Q2W) and 42/55 (76.4%; Q4W) patients from ADvocate1&2 and 26/31 (83.9%; Q2W) and 11/14 (78.6%; Q4W) patients from ADhere. EASI 75 was maintained by 65/68 (95.6%; Q2W) and 77/80 (96.3% Q4W) ADvocate1&2 patients and 39/41 (95.1%; Q2W) and 24/25 (96.0%; Q4W) ADhere patients at W104. In patients who achieved EASI 75 at W16, EASI 90 was achieved by 56/68 (82.4%; Q2W) and 66/80 (82.5%; Q4W) ADvocate1&2 patients and 35/41 (85.4%; Q2W) and 18/25 (72.0%; Q4W) ADhere patients at 104W.During ADjoin, 166/267 (62.2%) patients from the subpopulations of ADvocate1&2 and ADhere who received LEB Q2W or Q4W in ADjoin reported adverse events (AEs), most of which were mild (31.5%, n=84) or moderate (27.0%, n=72) in severity. Serious AEs were reported by 10 (3.8%) patients. There was one death in the ADhere Q2W arm. Six (2.3%) patients reported AEs leading to treatment discontinuation. The safety profile of LEB in ADjoin is consistent with that observed during ADvocate1&2 and ADhere. Conclusions: Efficacy outcomes were maintained long-term, over 2 years of continuous LEB treatment, in both LEB250mg Q2W and Q4W arms. The safety profile of LEB in ADjoin is consistent with previous LEB studies in patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]