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Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited treatment options for adolescents with moderate-to-severe disease. Lebrikizumab, a monoclonal antibody targeting interleukin (IL)-13, demonstrated clinical benefit in previous Phase 3 trials: ADvocate1 (NCT04146363), ADvocate2 (NCT04178967), and ADhere (NCT04250337). We report 52-week safety and efficacy outcomes from ADore (NCT04250350), a Phase 3, open-label study of lebrikizumab in adolescent patients with moderate-to-severe AD. The primary endpoint was to describe the proportion of patients who discontinued from study treatment because of adverse events (AEs) through the last treatment visit. Methods: Adolescent patients (N = 206) (≥ 12 to < 18 years old, weighing ≥ 40 kg) with moderate-to-severe AD received subcutaneous lebrikizumab 500 mg loading doses at baseline and Week 2, followed by 250 mg every 2 weeks (Q2W) thereafter. Safety was monitored using reported AEs, AEs leading to treatment discontinuation, vital signs, growth assessments, and laboratory testing. Efficacy analyses included Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Body Surface Area (BSA), (Children's) Dermatology Life Quality Index ((C)DLQI), and Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression. Results: 172 patients completed the treatment period. Low frequencies of SAEs (n = 5, 2.4%) and AEs leading to treatment discontinuation (n = 5, 2.4%) were reported. Overall, 134 patients (65%) reported at least one treatment-emergent AE (TEAE), most being mild or moderate in severity. In total, 62.6% achieved IGA (0,1) with ≥ 2-point improvement from baseline and 81.9% achieved EASI-75 by Week 52. The EASI mean percentage improvement from baseline to Week 52 was 86.0%. Mean BSA at baseline was 45.4%, decreasing to 8.4% by Week 52. Improvements in mean change from baseline (CFB) to Week 52 were observed in DLQI (baseline 12.3; CFB − 8.9), CDLQI (baseline 10.1; CFB − 6.5), PROMIS Anxiety (baseline 51.5; CFB − 6.3), and PROMIS Depression (baseline 49.3; CFB − 3.4) scores. Conclusions: Lebrikizumab 250 mg Q2W had a safety profile consistent with previous trials and significantly improved AD symptoms and quality of life, with meaningful responses at Week 16 increasing by Week 52. Trial registration: ClinicalTrials.gov identifier, NCT04250350. Plain Language Summary: Lebrikizumab in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis Atopic dermatitis is a chronic relapsing inflammatory skin disease that affects up to 15% of adolescents worldwide, with up to 50% suffering from moderate-to-severe disease. Signs and symptoms include dry, cracked skin; redness; itching; and painful lesions, which can negatively affect quality of life and lead to complications, including skin infections. Adolescents also report increased rates of anxiety and stress. Lebrikizumab is a novel monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, the key cytokine in atopic dermatitis, blocking the downstream effects of IL-13 with high potency. Lebrikizumab has been shown previously to improve symptoms of atopic dermatitis, including itch, skin clearance, and quality of life in ADvocate1, ADvocate2 and ADhere. The ADore study aimed to evaluate the safety and efficacy of lebrikizumab in adolescents with moderate-to-severe atopic dermatitis. Investigators recruited patients ≥ 12 to < 18 years old, weighing ≥ 40 kg, from Australia, Canada, Poland, and the US who were diagnosed with moderate-to-severe atopic dermatitis. These patients received a loading dose of 500 mg of lebrikizumab at Weeks 0 and 2, followed by 250 mg every 2 weeks for 52 weeks. The safety profile of lebrikizumab was consistent with previously published reports, with mostly mild or moderate adverse events, which did not lead to treatment discontinuation. Lebrikizumab improved skin clearance; 62.6% of patients had clear or almost clear skin by the end of the trial. Lebrikizumab also improved the patients' quality of life. These safety and efficacy results support lebrikizumab's role in treating adolescents with moderate-to-severe atopic dermatitis. D_n9HEaRPQDPZd1tfRjK-9 Safety and Efficacy of Lebrikizumab in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis: A 52-Week, Open-Label, Phase 3 Study (MP4 44681 KB) [ABSTRACT FROM AUTHOR]

Background Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13. Objectives To evaluate the efficacy and safety of lebrikizumab monotherapy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) over 52 weeks of treatment in ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Methods Patients who responded to lebrikizumab 250 mg every 2 weeks (Q2W) at the end of the 16-week induction period were re-randomized 2 : 2 : 1 to receive lebrikizumab Q2W, lebrikizumab 250 mg every 4 weeks (Q4W) or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. Response at week 16 was defined as achieving a 75% reduction in Eczema Area Severity Index (EASI 75) or an Investigator's Global Assessment (IGA) of 0 or 1, with a ≥ 2-point improvement and no rescue medication use. Multiple imputation was used to handle missing data. Intermittent use of topical therapy was permitted during the maintenance period. Results After 52 weeks, an IGA of 0 or 1 with a ≥ 2 point improvement was maintained by 71.2% of patients treated with lebrikizumab Q2W, 76.9% of patients treated with lebrikizumab Q4W and 47.9% of patients in the lebrikizumab withdrawal arm. EASI 75 was maintained by 78.4% of patients treated with lebrikizumab Q2W, 81.7% of patients treated with lebrikizumab Q4W and 66.4% of patients in the lebrikizumab withdrawal arm at week 52. Across treatment arms, proportions of patients using any rescue therapy were 14.0% (ADvocate1) and 16.4% (ADvocate2). During the combined induction and maintenance periods of ADvocate1 and ADvocate2, 63.0% of lebrikizumab-treated patients reported any treatment emergent adverse event, with most events (93.1%) being mild or moderate in severity. Conclusions After a 16-week induction period with lebrikizumab Q2W, lebrikizumab Q2W and Q4W maintained similar improvement of the signs and symptoms of moderate-to-severe AD, with a safety profile consistent with previously published data. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) can greatly impact quality of life in adolescents, and improved management is needed. Lebrikizumab, a high-affinity monoclonal antibody targeting interleukin (IL)-13, demonstrated clinical benefit in Phase 3 trials: ADvocate1, ADvocate2 and ADhere. This study aims to report 52-week safety and efficacy outcomes from ADore (NCT04250350), a Phase 3, open label study of lebrikizumab in adolescent patients with moderate-to-severe AD. Eligible adolescents (n = 206) (≥12 to <18 years; weighing ≥40 kg) received 500-mg loading doses at baseline and Week 2, and 250-mg lebrikizumab subcutaneous injections every 2-weeks (Q2W) for 52-weeks. Safety was monitored using adverse events (AEs), AEs leading to treatment discontinuation, vital signs and laboratory testing. Efficacy analyses included Investigator Global Assessment (IGA) and Eczema Area and Severity Index (EASI). A total of 172 patients completed the treatment period. Low frequencies of AEs leading to treatment discontinuation (2.4%) and SAEs (2.4%) were reported. Overall, 134 (65.0%) patients reported at least one treatment-emergent adverse event, most being mild or moderate in severity, including 14 (6.8%) conjunctivitis events. Efficacy was rapid, with 14.4% achieving IGA (0,1) at Week 4, increasing to 46.3% at Week 16 and 62.6% at Week 52. The EASI-75 was 28.6% at Week 4, 73.2% at Week 16, and 81.9% at Week 52. The mean percent improvement from baseline to Week 52 in EASI was 86.0%. Lebrikizumab open-label 250-mg Q2W had a safety profile in adolescents with moderate-to-severe AD, which was consistent with previous trials, with 2.4% treatment discontinuation due to AEs. Lebrikizumab demonstrated efficacy, with 81.9% of patients achieving EASI-75 and 62.6% achieving IGA (0,1) at Week 52. [ABSTRACT FROM AUTHOR]

LAVOLTA (L)I, LII and ACOUSTICS were randomized, placebo-controlled, double-blinded, Phase 3 trials of lebrikizumab, a monoclonal antibody targeting interleukin-13, in patients with uncontrolled asthma (LI, NCT01867125; LII, NCT01868061; ACOUSTICS, NCT01875003). These studies failed to provide consistently significant efficacy results in uncontrolled asthma. This study aims to report pooled safety analysis of lebrikizumab in patients during the 52-week placebo-controlled period from the three clinical trials. Adults in LI and LII, adolescents (12–17 years) in ACOUSTICS, with uncontrolled asthma, prebronchodilator forced expiratory volume in 1 s 40–90% predicted and stable background therapy were randomized 1 : 1 : 1 to lebrikizumab 125 or 37·5 mg or placebo (PBO) subcutaneously once every 4 weeks. Safety analyses were based on all patients who received at least one dose of study drug, with patients grouped by assigned treatment. Safety was assessed using summary of adverse events (AEs). The proportions of patients who experienced treatment-emergent AEs [combined lebrikizumab doses (LEB), 1281 (77%) of 1661 patients vs. PBO, 650 (78%) of 883 patients], serious AEs (7.6% vs. 8.5%) and AEs leading to study drug discontinuation (3.4% vs. 3.6%) were similar between LEB and PBO. One death occurred in the PBO group. Similar frequencies of key safety events, including conjunctivitis (LEB, 1.6%; PBO, 1.7%), infections and infestations (LEB, 51.6%; PBO, 50.7%), and eosinophil-related disorders (LEB, 0.2%; PBO, 0.2%) were noted; higher frequency of eosinophilia (>500 eosinophils/mm3) was reported (LEB, 1.1%; PBO, 0%). The safety profile was similar between lebrikizumab and placebo in adults and adolescents with uncontrolled asthma. [ABSTRACT FROM AUTHOR]

Lebrikizumab (LEB) is a monoclonal antibody that binds with high affinity to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. To report integrated safety information in adult and adolescent patients with moderate-to-severe atopic dermatitis treated with LEB, from an integrated safety analysis of eight clinical Phase 2 and 3 trials. These data include adult and adolescent patients who received at least one dose of study drug from a total of eight atopic dermatitis clinical trials: ADvocate1, ADvocate2, ADhere, ADore, ADjoin (ongoing), ARBAN, TREBLE and a Phase 2b study. Treatment duration ranged from a single dose to 100 weeks. This analysis includes all placebo-controlled Week 0- to 16-safety data in patients treated with LEB 250 mg every 2 weeks (LEBQ2W, n = 783) compared with placebo (n = 404) known as ALL PC Weeks 0–16, and all patients who received at least one dose of LEB (n = 1720) known as ALL LEB. Conjunctivitis cluster is defined by MedDRA-preferred terms of conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis and giant papillary conjunctivitis. Exposure adjusted incidence rates (IR) are provided as per 100 patient-years. In ALL PC Weeks 0–16 analysis, the frequency of treatment-emergent adverse events (TEAE) was 49.2% in LEBQ2W (n = 384) compared with 53.1% in placebo (n = 215). The majority of TEAEs reported were mild or moderate in severity with 2.3% (n = 18) reported as severe in LEBQ2W and 4.4% (n = 18) in placebo. Serious adverse events (SAEs) were reported by 1.3% (n = 10) in LEBQ2W and 1.9% (n = 8) in placebo. No deaths reported in LEBQ2W and one death in placebo. The most frequently reported TEAE in LEBQ2W was conjunctivitis and in placebo was atopic dermatitis. Conjunctivitis cluster was reported by 8.5% (n = 67) in LEBQ2W and 2.5% (n = 10) in placebo. All conjunctivitis cluster events were mild or moderate. Injection site reactions (ISRs) were reported by 2.6% (n = 20) in LEBQ2W and 1.5% (n = 6) in placebo. Adverse events leading to discontinuation were reported by 2.3% (n = 18) in LEBQ2W and 1.4% (n = 6) in placebo. In ALL LEB, the frequency of TEAEs was 64.3% (n = 1106, IR: 137.9), with the majority being mild or moderate in severity. Severe TEAEs were reported by 5.3% (n = 91). The incidence rates of TEAE did not increase with duration of treatment exposure. The SAEs were reported by 3.3% (n = 56, IR: 3.5). Three (0.2%) deaths occurred in ALL LEB. Conjunctivitis cluster was reported by 10.6% (n = 183, IR:12.2) with the majority being mild or moderate in severity and 0.3% (n = 6) being reported as severe. The ISRs were reported by 3.1% (n = 53, IR: 3.3). Adverse events leading to discontinuation were reported by 4.2% (n = 73, IR: 4.5). The overall safety profile for lebrikizumab consisted of AEs that were mostly nonserious, mild or moderate in severity, and did not lead to treatment discontinuation. Safety profile was similar in both adults and adolescents. [ABSTRACT FROM AUTHOR]

Lebrikizumab (LEB) is a novel, high-affinity monoclonal anti - body that selectively binds to interleukin (IL)-13. To evaluate the efficacy and safety of LEB monotherapy in patients with moderate-to-severe atopic dermatitis (AD) in two identical phase 3 trials ADvocate1 (ADv1) and ADvocate2 (ADv2). Patients who responded to LEB 250 mg every 2 weeks (LEB Q2W) at the end of the 16-week induction period were re-randomized in a 2 : 2 :1 ratio to receive LEB Q2W, LEB 250 mg every 4 weeks (LEB Q4W) or placebo (LEB withdrawal) for an additional 36 weeks. Response, at week 16, was defined as achieving an IGA (0, 1) with a ≥2-point improvement or EASI75 and no use of rescue medication. Efficacy outcomes reported at week 52 included IGA (0, 1), EASI 75, ≥4-point reduction in Pruritis Numeric Rating Scale (NRS), EASI 90 and DLQI ≥4-point. Safety analysis was conducted on all patients who received ≥1 dose of LEB. Patients maintained IGA (0, 1) in LEB Q2W (ADv1, 75.8%; ADv2, 64.6%), LEB Q4W (ADv1, 74.2%; ADv2, 80.6%) and LEB withdrawal (ADv1, 46.5%; ADv2, 49.8%). Maintenance of EASI75 was, in LEB Q2W (ADv1, 79.2%; ADv2, 77.4%), LEB Q4W (ADv1, 79.2%; ADv2, 84.7%) and LEB withdrawal (ADv1, 61.3%; ADv2, 72.0%). For Pruritus NRS ≥4-point improvement from baseline, patients-maintained improvement in the LEB Q2W (ADv1, 81.2%; ADv2, 90.3%), LEB Q4W (ADv1, 80.4%; ADv2, 88.1%) and LEB withdrawal (ADv1, 65.4%; ADv2, 67.6%). Maintenance of EASI90 was, in LEB Q2W (ADv1, 66.1%; ADv2, 61.5%), LEB Q4W (ADv1, 66.6%; ADv2, 67.4%) and LEB withdrawal (ADv1, 45.5%; ADv2, 36.9%). DLQI ≥4-point improvement from baseline was LEB Q2W (ADv1, 64.0%; ADv2, 59.0%), LEB Q4W (ADv1, 62.7%; ADv2, 73.0%) and LEB withdrawal (ADv1, 57.7%; ADv2, 45.5%). TEAEs were reported by 58.1% (ADv1) and 67.8% (ADv2) LEB-treated patients at week 52. Serious adverse events were reported by 3.3% of ADv1 patients and 2.7% of ADv2 patients. In ADv1 and ADv2, 2.3% and 3.9% of patients reported an adverse event leading to treatment discontinuation, respectively. Both LEB Q2W and LEB Q4W maintained improvement in all reported outcomes for the treatment of moderate-to-severe AD through 52 weeks. The safety profile was consistent with previously published data. [ABSTRACT FROM AUTHOR]

Lebrikizumab is an injectable, IgG4 monoclonal antibody that selectively binds to interleukin-13 with high affinity. Injection-site reactions (ISRs) are localized adverse events in the immediate site of administration of a drug and are common with injectable therapies. This analysis reports ISRs in patients from eight lebrikizumab (LEB) clinical trials in atopic dermatitis. To report ISRs in patients with moderate-to-severe atopic dermatitis treated with LEB, from an integrated safety analysis of phase 2 and 3 LEB clinical trials. These data sets include adolescents and adult patients who received at least one dose of LEB from a total of eight atopic dermatitis clinical trials, including four 16-week placebo-controlled clinical trials. Eight trials consist of: ADvocate1, ADvocate2, ADhere, ADore, ADjoin (ongoing), ARBAN, TREBLE and Phase 2b study. Treatment duration ranged from a single dose to 100 weeks. ISRs were defined using the preferred terms from the Medical Dictionary for Regulatory Activities high-level term, injection site reactions, excluding terms related to joints. This analysis includes ISRs frequencies in patients treated with LEB compared to placebo (ALL PC week 0–16), and all patients who received any dose of LEB (ALL LEB), and reports ISRs type, exposure adjusted incidence rates (EAIR) per 100 patient-years, the timing of ISRs occurrence, and ISRs leading to discontinuation. In the ALL PC week 0–16 analysis, 2.6% (n=20/783, EAIR 9.0) of patients in the LEB group reported ISRs vs. 1.5% (n = 6/404 EAIR 5.4) in the placebo group. Injection site pain (n = 7, 0.9%) and injection site erythema (n = 7, 0.9%) were the most frequent reactions reported in the LEB group. Most ISRs were mild or moderate, with only 1 (0.1%) severe event. In the ALL LEB analysis, 3.1% of patients reported ISRs (n = 53/1720, EAIR 3.3). Injection site pain (n = 16, 0.9%) and injection site erythema (n =12, 0.7%) were the most frequent reactions. Almost all reports were mild or moderate, with 3 (0.2%) severe. The incidence of ISRs did not increase with a longer duration of LEB expo - sure. The majority of ISRs were reported between weeks 0 and 16 ( n = 38, 2.2%). The frequency of ISRs from week 16 to 32 was 1.0% (n = 15), from week 32 to 48 was 0.4% ( n = 4) and from week 48 to 64 was 0.2% (n =2). Treatment discontinuation due to ISRs occurred in a few patients (n =5, 0.3%). Overall, a low proportion of patients reported ISRs (<3%) with a numerically higher frequency of LEB-treated patients who reported ISRs compared to placebo (1.5%). Most events were mild or moderate in severity, did not lead to treatment discontinuation, occurred within the first 16 weeks of treatment, and ISRs incidence did not increase with a longer duration of exposure. [ABSTRACT FROM AUTHOR]