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Introduction: Lebrikizumab is a novel monoclonal antibody with established efficacy in patients with moderate-to-severe atopic dermatitis (AD) in multiple Phase 3 trials. One of the ultimate treatment goals for patients with moderate-to-severe AD is to achieve stable disease control without concern for planning future life events. Methods: In ADvocate1 and ADvocate2, lebrikizumab-treated patients meeting the protocol-defined response criteria at Week 16 were re-randomized 2:2:1 to receive lebrikizumab every 2 weeks (Q2W), lebrikizumab every 4 weeks (Q4W), or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. In this post hoc analysis, we evaluated the proportions of patients with no or minimal fluctuations of efficacy during the 36-week maintenance period and plotted individual patient trajectories. We defined no or minimal fluctuations as achieving and maintaining the defined endpoint (≥ 75% improvement in the Eczema Area and Severity Index [EASI 75], ≥ 90% improvement in EASI, Pruritus Numeric Rating Scale [NRS] ≥ 4-point improvement, or Pruritus NRS ≥ 3-point improvement) for ≥ 80% of the study visits. If patients used rescue medication, discontinued treatment, or transferred to the escape arm, data collected at or after the event were imputed as non-response. Results: The proportions of lebrikizumab responders who maintained EASI 75 with no or minimal fluctuations were 70.8% (lebrikizumab Q2W), 71.2% (lebrikizumab Q4W), and 60.0% (lebrikizumab withdrawal). Of the patients with baseline Pruritus NRS ≥ 4 and who achieved ≥ 4-point improvement at Week 16, 66.1% (lebrikizumab Q2W), 62.7% (lebrikizumab Q4W), and 55.2% (lebrikizumab withdrawal) maintained ≥ 4-point Pruritus NRS improvement with no or minimal fluctuations. Conclusions: Patients who met the response criteria at Week 16 and continued treatment with lebrikizumab Q2W or Q4W demonstrated a stable response with no or minimal fluctuations of efficacy in measures of skin and itch up to Week 52. Clinical Trial Registration: NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2). Plain Language Summary: Atopic dermatitis, also known as atopic eczema (or just eczema), is a common skin disease that causes itchy, dry skin. Patients with eczema are often unsure of when disease flares will happen, even while receiving treatment. In two global studies, ADvocate1 and ADvocate2, lebrikizumab improved the signs and symptoms of moderate-to-severe eczema after 16 weeks of treatment. Most of these patients also saw improvement up to 52 weeks. We wanted to know if patients continued to feel better between Week 16 and Week 52. Patients who responded to lebrikizumab after 16 weeks were given lebrikizumab every 2 weeks, lebrikizumab every 4 weeks, or placebo every 2 weeks. We tested how many patients experienced stable response to therapy, which we said was maintaining the same level of improvement on skin signs and itch symptoms for at least 80% of study visits from Week 16 to Week 52. In patients treated with lebrikizumab every 2 weeks or every 4 weeks, we saw that about seven of every ten patients maintained a stable response in skin improvement and about six of every ten patients maintained stable response in itch symptoms. In patients who stopped lebrikizumab therapy, six out of every ten patients maintained a stable skin improvement and more than five of every ten patients maintained a stable improvement in itch symptoms. In ADvocate1 and ADvocate2, most lebrikizumab-treated patients showed a stable response over time on skin and itch with dosing every 2 weeks or every 4 weeks. [ABSTRACT FROM AUTHOR]

Introduction: Alopecia areata (AA) is an autoimmune disease associated with high rates of emotional and psychosocial distress. The analysis reported here describes the evolution of measures assessing health-related quality of life (HRQoL) and symptoms of anxiety and depression up to week 104 in patients who achieved sustained scalp hair regrowth during treatment with baricitinib in the BRAVE-AA phase III trials. Methods: This post-hoc analysis included data from the double-blind, parallel-group, randomized, placebo-controlled phase III trials BRAVE-AA1 (ClinicalTrials.gov number: NCT03570749) and BRAVE-AA2 (ClinicalTrials.gov number: NCT03899259). Adults with severe AA (defined as a Severity of Alopecia Tool [SALT] score ≥ 50) randomized to baricitinib 4 mg or baricitinib 2 mg at baseline who achieved SALT score ≤ 20 by week 36 and maintained SALT score ≤ 20 through week 104 on the same dose of baricitinib were included in this analysis of integrated data. Scalp hair regrowth (SALT score) and improvements in Skindex-16 AA Scale and Hospital Anxiety and Depression Scale (HADS) domain scores were analyzed over the 104-week period using descriptive statistics. Results: In total, 131 patients (88 on baricitinib 4 mg and 43 on baricitinib 2 mg) were included in this analysis. Across the two groups, the mean age (standard deviation) was 37.2 years (12.7), and 84 (64.1%) patients were female. The interquartile range) for time to achieve a SALT score ≤ 20 for patients treated with baricitinib 4 mg and baricitinib 2 mg was 13.1 and 19.6 weeks, respectively. By week 104, 91% (baricitinib 2 mg) and 96% (baricitinib 4 mg) of patients had achieved a SALT score ≤ 10 on baricitinib treatment. In both groups, progressive improvements in the Skindex-16 AA and HADS domain scores were observed up to week 104. Conclusion: This analysis of adults with severe AA treated with baricitinib revealed that achievement of sustained clinically meaningful scalp hair regrowth (SALT score ≤ 20) was associated with improvements in both measures of HRQoL and symptoms of anxiety and depression up to week 104. [ABSTRACT FROM AUTHOR]

Background: Lebrikizumab improved itch, interference of itch on sleep, and quality of life (QoL) in patients with moderate-to-severe atopic dermatitis (AD), in two Phase 3 trials at 16weeks compared to placebo. Objectives: We assess improvements in itch and sleep interference due to itch and their impact on QoL measurements after treatment. Methods: Data were analyzed from ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) in patients with moderate-to-severe AD. QoL was evaluated using Dermatology Life Quality Index (DLQI) at Week 16 in patients (>16years of age) who were itch responders/non-responders (defined as ≥4-point improvement in Pruritus Numeric Rating Scale) or Sleep-Loss Scale responders/non-responders (defined as ≥2-point improvement in itch interference on sleep). Results: In ADvocate1 and ADvocate2, significantly greater proportions of itch responders had a clinically meaningful improvement in measures related to QoL (DLQI scores (0/1), ≤5 DLQI total score and ≥4-point DLQI improvement) compared to itch non-responders. In both studies, a significantly greater proportion of Sleep-Loss Scale responders, reported a DLQI score of (0/1), DLQI total score of ≤5 and DLQI improvement of ≥4 points compared to Sleep-Loss Scale non-responders. Conclusions: Improvement in itch and sleep interference due to itch is associated with improvement in the QoL of patients after treatment with lebrikizumab for moderate-to-severe AD. ClinicalTrials.gov registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2). [ABSTRACT FROM AUTHOR]

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]

The article discusses the results of two phase III clinical trials, ADvocate1 and ADvocate2, which examined the efficacy and safety of lebrikizumab monotherapy in patients with moderate-to-severe atopic dermatitis (AD). The trials found that lebrikizumab significantly improved patient-reported itch and reduced sleep loss due to itch. The improvements in itch and sleep loss were observed as early as the first few days of treatment and were consistent with previous studies on lebrikizumab. The study was funded by Dermira, a subsidiary of Eli Lilly and Company, and medical writing assistance was provided by ProScribe–Envision Pharma Group. [Extracted from the article]

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]

Introduction/Background Lebrikizumab (LEB) is a novel monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) are identically designed Phase 3 trials that evaluated LEB as a monotherapy treatment for moderate-to-severe atopic dermatitis (AD). Many patients who met the protocol-defined response criteria at Week 16, defined as achieving ≥75% improvement in the Eczema Area and Severity Index (EASI 75) or an Investigator's Global Assessment of 0 or 1 (IGA 0/1) without use of rescue therapy, maintained a deep response up to Week 521. Deep response was defined as maintaining an IGA 0 (clear skin), a 100% improvement in the Eczema Area and Severity Index (EASI 100), or a Pruritus Numeric Rating Scale score of 0 or 1 (Pruritus NRS 0/1). Patients completing Week 52 were given the option to roll over into a long-term extension (LTE) study, ADjoin (NCT04392154), allowing the opportunity to analyze deep response for a longer period of time. This analysis supports the evolution of AD treatment goals toward maintaining higher efficacy thresholds for a longer duration. Objectives To present the long-term maintenance of LEB's depth of response for up to 104 weeks of treatment (52 weeks in the ADvocate studies and 52 weeks in the ADjoin study). Methods Patients entering ADjoin from ADvocate1 and ADvocate2 continued taking the same LEB dose as the parent study. Patients receiving placebo (LEB withdrawal) during the maintenance period of ADvocate1 and ADvocate2 transitioned to receive LEB every 2 weeks (Q2W) during ADjoin (data not included in this analysis). The proportion of patients achieving IGA and EASI responses were calculated from the LEB-treated patients who were IGA 0/1 or EASI 75 responders, respectively, at Week 16 in ADvocate1 and ADvocate2. The proportion of patients achieving a Pruritus NRS 0/1 response were calculated from the LEB patients who were per protocol responders at Week 16 of ADvocate1 and ADvocate2. Each patient's absolute Pruritus NRS score was calculated by averaging daily scores from the previous seven days with at least one nonmissing value. The weekly score was then rounded to the nearest integer. Consistent with common reporting practices for LTE studies, this post hoc analysis reports observed data which were analyzed regardless of rescue medication use or treatment discontinuation. Results From Week 52 to Week 104, the proportion of IGA 0 responders was maintained and slightly increased in patients treated with LEB Q2W (50.8% [N=59] to 52.3% [N=44]) and LEB every 4 weeks (Q4W; 43.5% [N=69] to 45.5% [N=55]). Greater improvements over the second year of treatment were seen in the proportion of EASI 100 responders treated with LEB Q2W (36.4% [N=88] to 39.7% [N=68]) and LEB Q4W (30.7% [N=101] to 41.3% [N=80]) as well as the proportion of Pruritus NRS 0/1 responders treated with LEB Q2W (46.3% [N=80] to 57.4% [N=61]) and Q4W (47.9% [N=94] to 55.4% [N=65]). Although rescue medication was allowed during ADjoin, a relatively low proportion of patients received ≥1 topical rescue medication in the LEB Q2W (9.8%) and LEB Q4W (15.2%) treatment arms. Conclusions These 2-year results demonstrate an extended maintenance of deep response in patients treated with LEB Q2W and LEB Q4W after responding to 16 weeks of LEB Q2W. Approximately 50% and 40% of LEB-treated patients sustained total skin clearance (IGA 0 and EASI 100, respectively) and more than 55% of LEB-treated patients reported no or minimal itch (Pruritus NRS 0/1). Maintenance treatment with LEB Q2W and LEB Q4W allows patients and providers to elevate their expected treatment goals in AD beyond EASI 75 and IGA 0/1 response. [ABSTRACT FROM AUTHOR]

Introduction Historically, atopic dermatitis (AD) was believed to affect primarily children. However, a recent meta-analysis of 17 studies reporting age of AD onset as >16 years found that the pooled proportion of adult-onset AD was 26.1%, and that AD onset can occur at all ages. Lebrikizumab (LEB) is a high-affinity monoclonal antibody which targets IL-13, the key cytokine implicated in AD. Objectives This analysis investigated the efficacy and safety of lebrikizumab in adults ≥60 years with moderate-to-severe AD. Methods Data for patients aged ≥60 years from two Phase 3 trials, ADvocate1 and ADvocate2, were pooled. A total of 98 patients ≥ 60 years participated in the ADvocate trials (N=28 placebo (PBO), N=70 LEB). Patients were treated with lebrikizumab 250mg every 2 weeks or PBO, for 16 Weeks. Baseline demographics and characteristics were recorded. Efficacy was assessed in the pooled modified intent to treat population at Week 16 with Investigator's Global Assessment (IGA) (0,1) with ≥2-point improvement, ≥75% improvement in Eczema Area and Severity Index (EASI 75), EASI percentage change from baseline (CFB), and Pruritus Numeric Rating Scale (NRS) ≥4-point improvement. Categorical outcomes were evaluated by Cochran Mantel Haenszel tests to compare treatment groups. Continuous outcomes were analyzed using the analysis of covariance model. Data collected after use of rescue medication or discontinuation due to lack of efficacy were imputed with non-responder imputation (NRI) for categorical endpoints, or baseline values for continuous endpoints. Data collected after discontinuation for other reasons were set to missing and missing data were imputed with multiple imputation. Safety was also assessed in the integrated modified safety population. Results The baseline mean age was 67.2 years (standard deviation [SD] 6.7, range 60-93) in LEB- treated patients and 69 years ([6.2], range 60-85) in PBO. The LEB-treated population was 62.9% male (n=44/70) vs PBO 46.4% (n=13/28). Race was comparable between groups. At baseline 67.1% LEB (n=47/70) and 57.1% PBO (n=16/28) patients had IGA 3, while 32.9% LEB (n=23/70) and 42.9% PBO (n=12/28) had IGA 4. Other baseline characteristics were comparable: EASI: LEB 26.1, [10.6] vs PBO 27.1, [8.1]; BSA: LEB 38.3, [19.8] vs. PBO 40.9, [18.1]; and Pruritus NRS: LEB 7.5, [2.0] vs PBO 7.4, [1.7]. At Week 16, IGA (0,1) was achieved by 34.5% LEB-treated patients vs 11% PBO (P=0.022). EASI 75 was achieved by 48.9% and 16.3% of LEB- and PBO-treated patients, respectively (P=0.004). Pruritus NRS with ≥4-point improvement was reported by 45.5% and 12.2% of LEB vs PBO, respectively (P=0.004). The mean percent CFB EASI was LEB -58.5% (SE 8.5) and PBO -29.4% (SE 11.1) (P=0.002). Safety results in the older adult population were consistent with the overall modified safety population. Conclusions At Week 16, efficacy and patient reported outcome endpoints were met in the older adult population. These results indicate that lebrikizumab is an effective treatment for moderate-to-severe AD in the adult population ≥60 years of age and has a consistent safety profile. [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]

Background: Baricitinib demonstrated efficacy in treating adults with moderate‐to‐severe atopic dermatitis (AD) in Phase 3 clinical trials. Objective: To examine long‐term efficacy of baricitinib combined with topical corticosteroids (TCS) in adult patients from a Phase 3 study, BREEZE‐AD7 (NCT03733301), enrolled in ongoing extension study, BREEZE‐AD3 (NCT03334435). Methods: Upon BREEZE‐AD7 completion, responders or partial responders (RPR [vIGA‐AD™ ≤2]) receiving baricitinib 2‐mg or 4‐mg + TCS maintained their original treatment doses in BREEZE‐AD3. Nonresponders (NR; vIGA‐AD 3,4) receiving baricitinib 2‐mg were rerandomized 1:1 to baricitinib 2‐mg or 4‐mg; NR receiving baricitinib 4‐mg remained on same dose. Integrated data from all patients (RPR + NR = baricitinib 4‐mg intent‐to‐treat [ITT] cohort) receiving continuous baricitinib 4‐mg in BREEZE‐AD7 through BREEZE‐AD3 were analysed, along with baricitinib 4‐mg or 2‐mg RPR cohorts. Primary endpoint was proportion of patients with vIGA‐AD (0,1) at Weeks 16, 36 and 52 (Weeks 32, 52 and 68 of continuous therapy). Additional outcomes included improvement in EASI75 and Itch NRS (up to Week 32). Missing data were imputed by last observation carried forward. Results: In baricitinib 4‐mg ITT cohort (N = 102), proportions of patients achieving vIGA‐AD (0,1) at Week 32, Week 52, and Week 68 were 21.6%, 26.5% and 23.5%; EASI75 were 46.1%, 40.2% and 43.1%, respectively. Itch NRS ≥4‐point improvement (Itch ≥4) were 47.3% at Week 16 and 40.6% at Week 32. In baricitinib 4‐mg RPR cohort (N = 63), proportions of patients achieving vIGA‐AD (0,1) at Week 32, Week 52 and Week 68 were 31.7%, 33.3% 34.9%, respectively; EASI75 were 57.1%, 49.2% and 49.2%, respectively. Itch ≥4 were 53.6% at Week 16 and 46.4% at Week 32. Corresponding proportions for baricitinib 2‐mg RPR cohort (N = 53) for vIGA‐AD (0,1) were 39.6%, 45.3% and 30.2%; EASI75 were 77.4%, 69.8% and 58.5%, respectively. Itch ≥4 were 56.3% at Week 16 and 47.9% at Week 32. Conclusion: Baricitinib 4‐mg and 2‐mg combined with TCS maintained clinically meaningful sustained efficacy over 68 weeks of continuous treatment. [ABSTRACT FROM AUTHOR]

Dupilumab is a treatment option for moderate-to-severe atopic dermatitis (AD). Not all patients treated with dupilumab achieve and maintain clinically meaningful responses; some experience adverse events and some discontinue dupilumab for other reasons. For these patients, prospective data are needed to better understand the efficacy of systemic medications administered after discontinuation of dupilumab. Lebrikizumab (LEB) is a monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. ADhere (NCT04250337) is a randomized, double-blind phase 3 trial evaluating the efficacy of lebrikizumab in combination with topical corticosteroids (TCS) over 16 weeks in adults and adolescents with moderate-to-severe AD. The results of this study, previously reported, showed statistically and clinically meaningful improvements in the signs and symptoms of AD in patients treated with LEB plus TCS vs. placebo (PBO) plus TCS. Of the patients randomized to LEB plus TCS, 20 reported prior dupilumab exposure. This study aims to evaluate the efficacy of LEB plus low to mid-potency TCS for the treatment of moderate-to-severe AD in the subpopulation of ADhere patients with prior exposure to dupilumab. At baseline, eligible patients in ADhere were randomized 2 : 1 to LEB 250 mg plus TCS or PBO plus TCS. Patients with prior exposure to dupilumab were permitted, with at least 8 weeks of washout prior to entering the study. Reported medical history was used to identify patients with prior exposure to dupilumab. Efficacy was measured through Investigator's Global Assessment (IGA), Eczema Area and Severity Index (EASI) and Pruritus Numeric Rating Scale (NRS). ADhere analyses were performed on a modified population, excluding 17 patients (from a single study site) whose eligibility could not be confirmed. All analyses are descriptive summaries using post hoc, as-observed analyses. The Pruritus NRS analysis only includes patients with baseline values ≥4. Observed results exclude data collected after use of rescue medication or treatment discontinuation. In ADhere, 211 patients were randomized 2 : 1 to LEB plus TCS (n = 145) or PBO plus TCS (n = 66). Of the patients randomized to LEB plus TCS, 20 reported prior dupilumab exposure. Of these 20 patients, the reason for dupilumab discontinuation was loss of response or inadequate response (10 patients), subject decision (four patients) or intolerance to medication (one patient). The final five patients discontinued due to affordability, treatment availability or unspecified reasons. In patients treated with LEB plus TCS, baseline disease characteristics were comparable between the overall LEB-treated population (n = 145) and the subpopulation with prior dupilumab exposure (n = 20). Of the 20 patients with prior dupilumab exposure, 13 patients presented with an IGA of three and seven patients presented with an IGA of 4. The mean [standard deviation (SD)] body surface area reported at baseline was 37.3 (15.7). The mean (SD) baseline scores for EASI and Pruritus NRS were 25.9 (8.1) and 7.8 (1.9), respectively. The mean (SD) duration since AD onset was longer in patients with prior dupilumab experience vs. the overall LEB-treated population 27.0 (22.5) vs. 21.0 (17.4) years, respectively]. In patients treated with LEB plus TCS, two of the 20 with prior dupilumab exposure were excluded due to use of rescue medication or treatment discontinuation. The IGA 0/1 with 2-point improvement was achieved by 6/18 patients, EASI 75 was achieved by 13/18 patients and Pruritus NRS 4-point improvement was achieved by 8/15 patients at Week 16. One patient reported rescue medication use. The results of this subpopulation analysis suggest that patients with prior dupilumab exposure can benefit from lebrikizumab treatment in combination with TCS. Additional data are needed to confirm this finding due to the small number of patients in the subpopulation. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is a chronic disease affecting children and adults and requires long-term treatment. Moderate-to-severe AD causes itching, which considerably impacts sleep. Interleukin (IL)-13 is the key cytokine in the skin of patients with AD. Lebrikizumab (LEB) 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. LEB has demonstrated efficacy and maintained improvement in measures of itch and sleep over 52 weeks in previous phase 3 trials. ADhere (NCT04250337) was a 16-week, randomized, double-blinded, placebo-controlled, phase 3 clinical trial, where patients were treated with LEB and topical corticosteroids (TCS) vs placebo and TCS. LEB responders from ADhere at week 16 were defined as having Investigator's Global Assessment response of 0 or 1 or reporting 75% improvement from ADhere baseline in Eczema Area and Severity Index who did not use rescue medications. ADhere LEB responders were rerandomized 2:1 into ADjoin (NCT04392154) for blinded treatment with LEB 250 mg every 2 weeks (Q2W) or every 4 weeks (Q4W), respectively, with TCS use as needed, for an additional 100 weeks with itch and sleep data being collected for the first 52 weeks. Objectives: The objectives of the study are to report the impact of LEB on itch and sleep improvements over a longer period (68 weeks) in ADhere week 16 LEB responders with moderate-to-severe AD who entered a long-term extension study, ADjoin. Methods: Itch was reported using the Pruritus Numeric Rating Scale (NRS), a patient-reported, single-item, daily, 11-point scale, where the minimal clinically important difference (MCID) is 3 points. Sleep loss due to itch was reported using the Sleep-Loss Scale, a patient-reported, single-item, 5-point scale, where the MCID is 1 point. We report =3-point improvement in Pruritus NRS among patients with baseline score at least 3, percent change from ADhere baseline (PCFB) in Pruritus NRS, Pruritus NRS (0,1), =1-point improvement in Sleep-Loss Scale score among patients with baseline score at least 1, =2-point improvement in Sleep-Loss Scale score among patients with baseline score at least 2 and PCFB in Sleep-Loss Scale score. All outcomes were reported at week 52 of ADjoin study, after a total of 68 weeks of LEB treatment. As observed analyses used all data collected. Results: At week 68, most patients reported maintaining ≥3-point improvement in Pruritus NRS treated with LEB Q2W (80.6%, 29/36) and LEB Q4W (88.9%, 16/18). Patients treated with LEB Q2W and LEB Q4W reported maintaining 65.3% and 59.4% improvement in Pruritus NRS at week 68 compared to ADhere baseline, respectively. At week 68, 45.9% (17/37) patients in LEB Q2W group and 31.6% (6/19) in LEB Q4W group reached Pruritus NRS of 0 or 1. At week 68, most patients reported maintaining ≥1-point improvement in Sleep-Loss Scale score treated with LEB Q2W (96.9%, 31/32) and LEB Q4W (85.7%, 12/14). Similarly, most patients reported maintaining ≥2-point improvement in Sleep-Loss Scale score treated with LEB Q2W (60.9%, 14/23) and LEB Q4W (75.0%, 6/8). Patients treated with LEB Q2W and Q4W reported maintaining 84.1% and 58.8% improvement in Sleep-Loss Scale score at week 68, respectively, compared to ADhere baseline. Conclusions: LEB + TCS maintained itch and sleep improvement at 68 weeks in patients with moderate-to-severe atopic dermatitis. [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]

The total treatment effect over placebo for changes in DLQI that could be accounted for by either itch or EASI was the indirect or mediation effect. With data from three monotherapy baricitinib phase III randomized clinical trials (RCTs), we conducted a posthoc mediator analysis to assess whether changes in itch or skin severity mediated the treatment effect over placebo on changes in health-related quality of life. [Extracted from the article]

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]

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, 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]