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Background: Lebrikizumab, a high-affinity monoclonal antibody targeting IL-13, previously demonstrated clinical efficacy in three randomized, double-blind, placebo-controlled Phase 3 trials that included adults and adolescents with moderate-to-severe atopic dermatitis (AD): ADvocate1, ADvocate2, and ADhere. Aim: This subset analysis evaluated 16-week physician- and patient-reported outcomes of lebrikizumab in the adolescent patients enrolled in these three trials. Methods: Eligible adolescents (≥12 to <18years weighing ≥40kg) were randomized 2:1 to subcutaneous lebrikizumab (500mg loading doses at baseline and Week 2 followed by 250mg every 2weeks) or placebo as monotherapy in ADvocate1&2, and in combination with topical corticosteroids (TCS) in the ADhere study. Week 16 analyses included clinical efficacy outcomes (IGA (0,1) with ≥2-point improvement, EASI 75, EASI 90), patient-reported Pruritus NRS ≥4-point improvement and Sleep-Loss Scale ≥2-point improvement. Results: Pooled ADvocate1&2 16-week results in lebrikizumab (N=67) vs placebo (N=35) were: IGA (0,1) 46.6% vs 14.3% (p<0.01), EASI 75 62.0% vs 17.3% (p<0.001), EASI 90 40.7% vs 11.5% (p<0.01), Pruritus NRS 48.9% vs 13.1% (p<0.01), and Sleep-Loss Scale 26.9% vs 6.9% (p=0.137). Corresponding results for ADhere, (lebrikizumab+TCS, N=32; placebo+TCS, N=14), were consistent. Conclusions: Lebrikizumab treatment demonstrated efficacy in improving the signs and symptoms of AD in adolescent patients, consistent with the ADvocate and ADhere overall population results. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) has different clinical presentations, pathophysiology, comorbidity frequencies, and genetic profiles in adult-onset vs childhood-onset disease. Based on these differences, it is plausible that treatment response would also be different between adult- and childhood-onset AD. Lebrikizumab, a novel, high affinity monoclonal antibody, selectively targeting IL-13 with high affinity and slow dissociation rate, has been approved in the EU, UK, and Japan and is under investigation in the US and elsewhere for the treatment of moderate-to-severe AD. Objectives To evaluate the Week-16 efficacy of lebrikizumab monotherapy by age of AD onset in adults and adolescents with moderate-to-severe AD from ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), identically-designed, randomized, double-blind, placebo-controlled phase 3 trials. Methods In ADvocate1 and ADvocate2, eligible patients were randomly allocated 2:1 to receive lebrikizumab 250 mg or placebo every 2 weeks. The date of AD onset was collected, and age of onset was calculated accordingly. Patients were stratified by age of AD-onset as ≤2, >2-to-<18, and ≥18 years. Efficacy was assessed at Week 16 with the proportion of patients with Investigator's Global Assessment score of 0 or 1 with ≥2-point improvement (IGA 0,1; the trials' primary endpoint); ≥75% (EASI 75) and ≥90% (EASI 90) improvement in the Eczema Area and Severity Index from baseline; ≥4-point Pruritus Numeric Rating Scale (NRS) improvement from baseline (with baseline score ≥4), and percentage change in total EASI from baseline. Data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders or set to baseline values. Data from patients who discontinued treatment for other reasons were set to missing and analyzed by multiple imputation. This was a post-hoc analysis conducted on the modified, pooled intent-to-treat population. Treatment-by-age subgroup interaction was assessed with logistic regression. Binary outcomes were analyzed by the Cochran-Mantel-Haenszel method, and continuous outcomes were analyzed with ANCOVA. Results At baseline, the numbers of patients treated with lebrikizumab and placebo, respectively, were 215 and 117 in the ≤2 years AD-onset subgroup, 178 and 103 in the >2-to-<18 years subgroup, and 171 and 67 in the ≥18 years subgroup. At baseline, the percentages of patients with ≥1 atopic comorbidity were 81% in the ≤2 years subgroup, 74% in the >2-to-<18 years subgroup, and 58% in the ≥18 years subgroup. At Week 16, treatment-by-age subgroup interactions were not significant at the 0.10 level for IGA 0,1; EASI 75; EASI 90; and Pruritus NRS 4-pt improvement. Within each subgroup, a higher proportion of lebrikizumab-treated compared with placebo-treated patients (p<0.001) achieved IGA 0,1 responses (≤2 years: 41% vs. 12%; >2-to-<18 years: 35% vs. 12%; ≥18 years: 38% vs. 12%), EASI 75 responses (≤2 years: 57% vs. 17%; >2-to-<18 years: 51% vs. 16%; ≥18 years: 58% vs. 20%), and EASI 90 responses (≤2 years: 38% vs. 10%; >2-to-<18 years: 32% vs. 9%; ≥18 years: 33% vs. 8%). Additionally, the least-squares mean percentage change from baseline in total EASI score for lebrikizumab and placebo, respectively, was -65% and -26% in the ≤2 years subgroup, -60% and -26% in the >2-to-<18 years subgroup, and -63% and -30% in the ≥18 years subgroup (p<0.001 for lebrikizumab vs. placebo in all subgroups). The proportion of lebrikizumab-treated patients who reported ≥4-point improvement in Pruritus NRS from baseline (baseline ≥4) was greater compared with placebo-treated patients ([N]; ≤2 years: 43% [201] vs. 11% [108]; >2-to-<18 years: 41% [161] vs. 14% [96]; ≥18 years: 45% [154] vs. 12% [60]; p<0.001). Conclusions Regardless of age of AD onset, lebrikizumab was associated with significant improvements in AD signs and symptoms compared with placebo over 16 weeks of treatment. [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]

Objective: To report the efficacy and safety of the approved ixekizumab (IXE) dose over 5 years from UNCOVER-3 (NCT01646177).Methods: Patients (N = 1346) were randomized 1:2:2:2 to receive subcutaneous injections of placebo, etanercept 50 mg twice weekly, or IXE 80 mg every 2 weeks or every 4 weeks after an initial dose of IXE 160 mg, respectively. At week 12, patients entered the long-term extension period with dosing of IXE every 4 weeks and could escalate to every 2 weeks after week 60. Efficacy was reported for the IXE every 2 weeks/every 4 weeks group of the intent-to-treat population. Safety was reported for patients who received at least 1 dose of IXE every 2 or every 4 weeks.Results: Using modified nonresponder imputation, 78.8%/67.1%/46.2% of patients receiving the approved dose of IXE every 2 weeks/every 4 weeks (n = 385) achieved ≥75%, ≥90%, or 100% improvement from baseline in the Psoriasis Area and Severity Index, respectively, at week 264; static Physician's Global Assessment score of 0/1 and 0 responses were 69.2% and 45.3%, respectively. Infections were the most observed treatment-emergent adverse event (72.7% of patients).Limitations: Lack of comparison treatment group after week 12.Conclusion: IXE demonstrates sustained efficacy and consistent safety through 264 weeks in patients using the approved dose. [ABSTRACT FROM AUTHOR]

Lebrikizumab, a high-affinity monoclonal antibody targeting IL-13, previously demonstrated clinical efficacy in adults and adolescents with atopic dermatitis (AD) in phase 3 trials. Here we evaluate 16-week efficacy outcomes of lebrikizumab in adolescent patients with moderate-to-severe AD from 3 randomized, double-blind, placebo-controlled phase 3 trials: ADvocate1, ADvocate2 and ADhere. Eligible adolescents (≥12 to <18 years weighing ≥40 kg) were randomized 2 : 1 to subcutaneous lebrikizumab (loading doses of 500 mg at Baseline and Week 2 followed by 250 mg every 2 weeks) or placebo in ADvocate1&2 as monotherapy, and in combination with topical corticosteroids (TCS) in ADhere. Efficacy analyses at Week 16 included IGA (0,1) with ≥2-point improvement, EASI-75, and Pruritus NRS ≥4-point improvement. Adolescent data from ADvocate1 and ADvocate2 were pooled, and ADhere data were analysed separately. ADvocate2 and ADhere analyses were performed on a modified population, excluding 10 adolescent patients from a single site whose eligibility could not be confirmed. Combined adolescent 16-week results from ADvocate1 and ADvocate2 [lebrikizumab (n = 67) vs. placebo (n = 35)] were IGA (0,1) with ≥2-point improvement from baseline 46.6% vs. 14.3% (P < 0.01), EASI-75 62.0% vs. 17.3% (P < 0.001) and Pruritus NRS ≥4-point improvement from baseline 48.9% vs. 13.1% (P < 0.01), respectively. The corresponding proportions in ADhere (lebrikizumab + TCS, n = 32; placebo + TCS, n = 14) were IGA (0,1) 57.3% vs. 28.6% (P = 0.071), EASI-75 88.0% vs. 57.1%, (P < 0.05) and Pruritus NRS 45.8% vs. 13.8%, (P = 0.078), respectively. Lebrikizumab treatment with or without TCS demonstrated clinical efficacy in adolescents with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Lebrikizumab demonstrated robust efficacy during the first 16 weeks of treatment in ADvocate1 and ADvocate2. This study aims to describe the 52-week results of lebrikizumab-treated patients who did not meet the protocol-defined criteria for response at 16 weeks of treatment. During the induction period, patients were randomized 2 : 1 to lebrikizumab 250 mg or placebo every 2 weeks (Q2W) for 16 weeks. Protocol-defined criteria for response were characterized as achieving a 75% Eczema Area and Severity Index (EASI75) or an Investigator's Global Assessment of 0 or 1 (IGA 0,1) with a ≥2-point improvement and without rescue medication use. At Week 16, patients from the lebrikizumab treatment arm, who did not reach the criteria for response, were assigned to the Escape arm (n = 215). These patients continued to receive lebrikizumab 250 mg Q2W for an additional 36 weeks. Endpoints and measurements included at week 52 were EASI75, EASI90, IGA (0,1) and pruritus. Pruritus was assessed using an 11-point Pruritus Numeric Rating Scale (NRS). Data are presented as observed results with no imputation for missing data. Pooled results for patients who did not respond to lebrikizumab and entered the escape arm show 36.1% achieved IGA (0,1) with 2-point improvement at Week 52. In the same population, 75.5% achieved EASI75, 44.2% achieved EASI90 and 66.4% reported 4-point improvement in Pruritus NRS. These results suggest that patients, who do not achieve protocol-defined response at 16 weeks of treatment, can be slow responders and derive benefit from continuing long-term therapy with lebrikizumab. [ABSTRACT FROM AUTHOR]