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Background: Lebrikizumab demonstrated statistically significant improvements in patients with moderate-to-severe atopic dermatitis at week 16 with a durable response up to week 52., Objective: To investigate the efficacy of lebrikizumab-treated patients at 52 weeks who did not achieve the ADvocate1 and ADvocate2 protocol-defined response criteria (≥75% improvement in the Eczema Area and Severity Index [EASI 75] or Investigator Global Assessment [IGA] 0/1 with ≥2-point improvement without rescue medication) after 16 weeks., Methods: This analysis includes observed data for patients who received lebrikizumab every 2 weeks during the induction period, did not achieve the protocol-defined response, and subsequently received open-label lebrikizumab treatment., Results: At week 16, 38.1% of lebrikizumab-treated patients entered the escape arm due to not achieving the response criteria. However, most of these patients had achieved ≥50% improvement in EASI (58.1%) by week 16. At week 52, 36.1% achieved IGA 0/1 with ≥2-point improvement, 75.5% achieved EASI 75, 44.2% achieved ≥90% improvement in EASI, and 66.4% reported ≥4-point Pruritus Numeric Rating Scale improvement., Limitations: This analysis assesses patients receiving open-label treatment with concomitant topical therapy allowed., Conclusion: Lebrikizumab-treated patients not achieving the protocol-defined response at week 16 can benefit from the continuation of longer-term therapy., (Copyright © 2024. Published by Elsevier Inc.)

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 <18 years weighing ≥40kg) were randomized 2:1 to subcutaneous lebrikizumab (500 mg loading doses at baseline and Week 2 followed by 250 mg every 2 weeks) 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.

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 16 weeks 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 (>16 years 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).

Introduction: Lebrikizumab, a high-affinity IgG4 monoclonal antibody that selectively inhibits interleukin-13 with high binding affinity and slow dissociation rate, prevents the formation of the interleukin-4Rα/interleukin-13Rα1 heterodimer receptor signaling complex. Here we report the impact of lebrikizumab on responses to two non-live vaccines in adult patients with moderate-to-severe atopic dermatitis (AD)., Methods: ADopt-VA (NCT04626297) was a double-blind, placebo-controlled, parallel-group, 16-week, phase 3 randomized study to assess the impact of lebrikizumab treatment on non-live vaccine immune responses, and efficacy and safety of lebrikizumab compared with placebo. Eligible patients included adults from 18 to 55 years of age with moderate-to-severe chronic AD who were randomly assigned 1:1 to lebrikizumab 250 mg every 2 weeks or placebo and stratified according to disease severity. The primary endpoints were the development of a booster response to tetanus toxoid and a positive antibody response to meningococcal conjugate vaccine (MCV), 4 weeks after administration of the corresponding vaccine., Results: At week 16, 73.6% of patients in the lebrikizumab group (n = 78/106) achieved Tdap booster response compared with 73.4% of patients in the placebo group (n = 58/79). MCV vaccine response was observed in 86.9% of patients in the lebrikizumab group (n = 86/99) and 75.0% of patients in the placebo group (n = 60/80). At week 16, IGA 0,1 with ≥ 2-point improvement from baseline was achieved by 40.6% (n = 51/125) of patients treated with lebrikizumab and 18.9% (n = 23/122) of patients who received placebo (p < 0.001). There was a higher proportion of patients achieving EASI 75 at week 16 in the lebrikizumab-treated patients (58.0%, n = 72/125) compared with placebo (32.7%, n = 40/122, p < 0.001)., Conclusions: Treatment with lebrikizumab did not impact response to non-live vaccines Tdap and MCV in this study. Lebrikizumab treatment had a significant degree of efficacy compared to placebo across multiple endpoints., Trial Registration: ClinicalTrials.gov identifier NCT04626297., (© 2024. The Author(s).)

Background: Sleep loss is a key factor contributing to disease burden in people with atopic dermatitis (AD). Mitigating itch to improve sleep is an important outcome of AD treatment. This study explored the content validity and measurement properties of the Sleep-Loss Scale, a single-item rating scale for assessing itch interference with sleep in clinical trials of AD treatments., Methods: Concept elicitation and cognitive debriefing interviews were conducted with 21 adults and adolescents (12-17 years of age) with moderate-to-severe AD to develop a conceptual model of patient experience in AD and explore the content validity of the scale. Data collected from adults with moderate-to-severe AD enrolled in a phase 2b study (NCT03443024) were used to assess Sleep-Loss Scale's psychometric performance, including reliability, construct validity, and ability to detect change. Meaningful within-patient change (MWPC) thresholds were also determined using anchor-based methods., Results: Qualitative findings from concept elicitation highlighted the importance of sleep-loss related to itch in AD. Debriefing analysis of the Sleep-Loss Scale indicated that the scale was relevant, appropriate, and interpreted as intended. Trial data supported good reliability, construct validity and ability to detect improvement. MWPC was defined as a 1-point improvement using trial data, a finding supported by qualitative data., Conclusions: The Sleep-Loss Scale provides a valid and reliable patient-reported measure of the impact of itch on sleep in patients with AD, and can detect change, indicating it is fit-for-purpose to evaluate the efficacy of AD treatments in moderate-to-severe patients., (© 2024. The Author(s).)

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease for which signs and symptoms have a negative impact on a patient's quality of life (QoL) and mental health. Here, we assess the impact of lebrikizumab on QoL and mental health after 16 weeks of treatment in patients with moderate-to-severe AD., Methods: Data were analyzed over 16 weeks from two separate phase 3, randomized, placebo-controlled, monotherapy trials (ADvocate1 and ADvocate2). Patient-reported outcomes were assessed using the following measures: Dermatology Life Quality Index (DLQI), EQ-5D-5L visual analogue scale (VAS), EQ-5D-5L index scores (UK and US), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression., Results: Treatment with lebrikizumab 250 mg every 2 weeks in two studies led to statistically significant improvements (based on nominal p values) versus placebo in DLQI since week 4 (the first timepoint assessed) for the following measures: change from baseline in DLQI total score (ADvocate1 - 7.8 vs - 2.8; ADvocate2 - 7.3 vs - 3.9), proportion of patients with DLQI ≥ 4-point improvement (ADvocate1 69.5% vs 36.2%; ADvocate2 60.5% vs 42.6%), DLQI total score ≤ 5 (ADvocate1 36.7% vs 8.8%; ADvocate2 29.6% vs 10.8%), and DLQI (0, 1) (ADvocate1 12.3% vs 1.7%; ADvocate2 9.2% vs 1.7%). Improvements in DLQI measures, EQ-5D-5L index scores (UK and US), and EQ-5D-5L VAS were sustained through week 16. Additionally, lebrikizumab improved PROMIS Anxiety and PROMIS Depression scores, and improvements were higher in patients with at least a mild score (≥ 55) versus placebo for PROMIS Anxiety (ADvocate1 - 7.43 vs - 1.51; ADvocate2 - 4.95 vs - 0.82) and PROMIS Depression (ADvocate1 - 7.42 vs - 2.46; ADvocate2 - 4.28 vs - 2.00)., Conclusions: Treatment with monotherapy 250 mg lebrikizumab for 16 weeks provided clinically meaningful improvements in outcomes related to QoL and mental health for patients with moderate-to-severe AD. Lebrikizumab-treated patients reported improvements in DLQI as early as week 4, the first measure since baseline., Trial Registration: ClinicalTrials.gov Registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2)., (© 2024. The Author(s).)

Background: Pruritus, or itch, is a key symptom of atopic dermatitis (AD); as such, mitigating itch is an important outcome of AD treatment. This study explored the content validity and measurement properties of the Pruritus Numeric Rating Scale (Pruritus NRS), a novel single-item scale for assessing itch severity in clinical trials of AD treatments., Methods: In this mixed-methods study, qualitative interviews were conducted with 21 people with moderate-to-severe AD (n = 15 adult, n = 6 adolescent) to develop a conceptual model of the patient experience in AD and explore the content validity of the Pruritus NRS. Data collected daily from adults with moderate-to-severe AD enrolled in a phase 2b study (NCT03443024) were used to assess the Pruritus NRS' psychometric performance, including reliability, construct validity, and responsiveness. Meaningful within-patient change (MWPC) thresholds were also determined using anchor-based methods., Results: Qualitative findings highlighted the importance of itch in AD, including severity, persistence, frequency, and daily life interference. Patient debriefing of the Pruritus NRS indicated that the scale was relevant, appropriate, and interpreted as intended. Trial data supported overall good psychometric properties. MWPC was defined as a 3-point improvement in Pruritus NRS score, a finding supported by qualitative data., Conclusions: The Pruritus NRS provides a valid and reliable patient-reported measure of itching severity in patients with moderate-to-severe AD, and can detect change, indicating it is fit-for-purpose to evaluate the efficacy of AD treatments in this population., Trial Registration: ClinicalTrials.gov identifier, NCT03443024., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest see Appendix S1 for the full Conflicts of Interest statement.

Background: Lebrikizumab is a monoclonal antibody that binds with high affinity to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency., Objectives: To report integrated safety of lebrikizumab in adults and adolescents with moderate-to-severe atopic dermatitis from phase 2 and 3 studies., Methods: Five double-blind, randomized placebo-controlled studies; one randomized open-label study; one adolescent open-label, single-arm study; and one long-term safety study were summarized in two datasets: (1) placebo-controlled week 0-16 (All-PC Week 0-16) in patients who received lebrikizumab 250 mg every 2 weeks (LEBQ2W) versus placebo and (2) patients who received any dose of lebrikizumab at any time during the studies (All-LEB). Exposure-adjusted incidence rates (IR)/100 patient-years (PY) are provided., Results: A total of 1720 patients received lebrikizumab (1637.0 PY exposure). In All-PC Week 0-16, the frequency of treatment-emergent adverse events (TEAEs) was similar between treatment groups; most events were nonserious and mild or moderate in severity. The most frequently reported TEAEs were atopic dermatitis (placebo) and conjunctivitis (LEBQ2W). Frequencies of conjunctivitis cluster were 2.5% (placebo) and 8.5% (LEBQ2W), and all events were mild or moderate (All-LEB 10.6%, IR, 12.2). Frequencies of injection site reactions were 1.5% (placebo) and 2.6% (LEBQ2W; All-LEB 3.1%, IR, 3.3). Frequencies of adverse events leading to treatment discontinuation were 1.4% (placebo) and 2.3% (LEBQ2W; All-LEB 4.2%, IR, 4.5)., Conclusion: The safety profile for lebrikizumab consisted of TEAEs that were mostly nonserious, mild or moderate in severity, and did not lead to treatment discontinuation. The safety profile was similar in both adults and adolescents., Clinicaltrials: GOV: NCT02465606, NCT02340234, NCT03443024, NCT04146363, NCT04178967, NCT04250337, NCT04250350, NCT04392154 Safety of lebrikizumab in adults and adolescents with moderate-to-severe atopic dermatitis: an integrated analysis of eight clinical trials (MP4 34165 KB)., (© 2023. The Author(s).)

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., Competing Interests: Conflicts of interest A.B. has served as a speaker (received honoraria) for AbbVie, Arcutis, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, Regeneron, Sanofi and UCB; served as a scientific adviser (received honoraria) for AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, AnaptysBio, Arcutis, Arena, ASLAN Pharmaceuticals, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly and Company, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, LEO Pharma, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome and Xencor; and has acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, ACELYRIN, Almirall, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly and Company, Evelo, Evommune, Galderma, Incyte, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sun Pharma and UCB Pharma. J.P.T. is an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Coloplast, OM Pharma, ASLAN Pharmaceuticals, Union Therapeutics, Eli Lilly and Company, LEO Pharma, Pfizer, Regeneron and Sanofi Genzyme; a speaker for AbbVie, Almirall, Eli Lilly and Company, LEO Pharma, Pfizer, Regeneron and Sanofi Genzyme; and has received research grants from Pfizer, Regeneron and Sanofi Genzyme. E.G.-Y. is a consultant for AbbVie, Almirall, Amgen, Asana Biosciences, Boehringer Ingelheim, Cara Therapeutics, Celgene, Concert, DBV, Dermira, DS Biopharma, Eli Lilly and Company, EMD Serono, Escalier, Galderma, Glenmark, Kyowa Kirin, LEO Pharma, Mitsubishi Tanabe, Pfizer, RAPT Therapeutics, Regeneron, Sanofi, Sienna Biopharma and Union Therapeutics; and reports institute grants for research from AbbVie, Almirall, Amgen, AnaptysBio, Asana Biosciences, Boehringer Ingelheim, Celgene, Dermavant, DS Biopharma, Eli Lilly and Company, Glenmark, Galderma, Innovaderm, Janssen, Kiniska, Kyowa Kirin, Leo Pharma, Novan, Pfizer, Ralexar, Regeneron, Sienna Biopharma, UCB and Union Therapeutics. T.B. has been a speaker and/or consultant and/or investigator for AbbVie, Affibody, Almirall, AnaptysBio, Arena, Asana Biosciences, ASLAN Pharmaceuticals, Bayer Health, BioVerSys, Boehringer-Ingelheim, Bristol Myers Squibb, Connect Pharma, Dermavant, Domain Therapeutics, EQRx, Galderma, Glenmark, GSK, Incyte, Innovaderm, IQVIA, Janssen, Kirin, Kymab, LEO Pharma, LG Chem, Lilly, L’Oréal, MSD, Novartis, Numab, OM Pharma, Pfizer, Pierre Fabre, Q32bio, RAPT, Sanofi/Regeneron and UCB; he is the founder and chairman of the board of the nonprofit biotechnology company Davos Biosciences. E.S.-B. has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AbbVie, Novartis, Almirall, LEO Pharma, Sanofi, Pfizer and Eli Lilly and Company. E.S. reports personal fees from AbbVie, Amgen, Arena Pharmaceuticals, ASLAN Pharmaceuticals, Boston Consulting Group, Collective Acumen (CA, USA), Dermira, Eli Lilly and Company, Evidera, Excerpta Medica, Forte Bio RX, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin Pharmaceutical Development, LEO Pharma, Medscape, Merck, Pfizer, Physicians World, Regeneron, Roivant, Sanofi Genzyme, Trevi Therapeutics, Valeant and WebMD. These potential conflicts of interest have been reviewed and managed by Oregon Health & Science University (OHSU). E.S. reports grants from (or served as principal investigator for) AbbVie, Amgen, Arcutis Biotherapeutics, ASLAN Pharmaceuticals, CorEvitas, Dermavant, Dermira, Eli Lilly, Incyte, Kymab, Kyowa Hakko Kirin, LEO Pharma, Pfizer, Regeneron, Sanofi and TARGET-DERM. These potential conflicts of interest have been reviewed and managed by OHSU. D.R. has received honoraria as a consultant for AbbVie, Abcuro, AltruBio, Arena, Boehringer-Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Incyte, Janssen, Kyowa Kirin, Eli Lilly and Company, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharmaceuticals, UCB and VielaBio; has received research support from AbbVie, Amgen, Bristol Meyers Squibb, Celgene, Dermira, Galderma, Incyte, Janssen, Eli Lilly and Company, Merck, Novartis, Pfizer, and Regeneron Pharmaceuticals; and has served as a paid speaker for AbbVie, Amgen, Bristol Meyers Squibb, Celgene, Incyte, Janssen, Eli Lilly and Company, Novartis, Pfizer, Regeneron Pharmaceuticals and Sanofi. H.E., E.M., C.R.N., Z.L., C.X., E.P. and M.M.-C. are employees of Eli Lilly and Company. E.G.G. is an employee of Almirall S.A. J.I.S. has received grants and/or personal fees from AbbVie, AFYX Therapeutics, Arena Pharmaceuticals, Asana BioSciences, Bluefin, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly and Company, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Luna Pharma, Menlo Therapeutics, Novartis, Pfizer, RAPT Therapeutics, Regeneron and Sanofi., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Importance: Lebrikizumab (LEB), a high-affinity monoclonal antibody targeting interleukin (IL)-13, demonstrated efficacy and safety in patients with moderate-to-severe atopic dermatitis (AD) during 16 weeks of monotherapy in a phase 2b trial, and two 52-week phase 3 trials., Objective: To evaluate efficacy and safety of LEB combined with low- to mid-potency topical corticosteroids (TCS) in patients with moderate-to-severe AD., Design, Setting, and Participants: The ADhere trial was a 16-week randomized, double-blinded, placebo (PBO)-controlled, multicenter, phase 3 clinical trial conducted from February 3, 2020, to September 16, 2021. The study was conducted at 54 outpatient sites across Germany, Poland, Canada, and the US and included adolescent (aged ≥12 to <18 years weighing ≥40 kg) and adult patients with moderate-to-severe AD. The treatment allocation ratio was 2:1 (LEB:PBO)., Interventions: Overall, 211 patients were randomized to subcutaneous LEB (loading dose of 500 mg at baseline and week 2, followed by 250 mg every 2 weeks [Q2W] thereafter) or PBO Q2W in combination with TCS for 16 weeks., Main Outcomes and Measures: Efficacy analyses at week 16 included proportions of patients achieving Investigator's Global Assessment score of 0 or 1 (IGA [0,1]) with 2 or more points improvement from baseline, and 75% improvement in the Eczema Area and Severity Index (EASI-75). Key secondary end points included evaluation of itch, itch interference on sleep, and quality of life. Safety assessments included monitoring adverse events (AEs)., Results: The mean (SD) age of patients was 37.2 (19.3) years, 103 (48.8%) patients were women, 31 (14.7%) patients were Asian, and 28 (13.3%) patients were Black/African American. At week 16, IGA (0,1) was achieved by 145 (41.2%) patients in the LEB+TCS group vs 66 (22.1%) receiving PBO+TCS (P = .01); corresponding proportions of patients achieving EASI-75 were 69.5% vs 42.2% (P < .001). The LEB+TCS group showed statistically significant improvements in all key secondary end points. Most treatment-emergent adverse events (TEAEs) were nonserious, mild or moderate in severity, and did not lead to study discontinuation. The TEAEs frequently reported in the LEB+TCS group included conjunctivitis (7 [4.8%]), headache (7 [4.8%]), hypertension (4 [2.8%]), injection site reactions (4 [2.8%]), and herpes infection (5 [3.4%]) vs 1.5% or less patient-reported frequencies in the PBO+TCS group. Similar frequencies of patient-reported serious AEs following LEB+TCS (n = 2, 1.4%) and PBO+TCS (n = 1, 1.5%)., Conclusions and Relevance: In this randomized phase 3 clinical trial, LEB+TCS was associated with improved outcomes in adolescents and adults with moderate-to-severe AD compared with TCS alone, and safety was consistent with previously reported AD trials., Trial Registration: ClinicalTrials.gov Identifier: NCT04250337.

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., Competing Interests: Conflicts of interest Dr Blauvelt has served as a scientific advisor and/or clinical study investigator for AbbVie, Aclaris, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly and Company, Forte, Galderma, Janssen, Leo, Novartis, Ortho, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma and as a paid speaker for AbbVie. Dr Lebwohl is an employee of Mount Sinai; receives research funds from AbbVie, Amgen, Arcutis, AstraZeneca, Boehringer Ingelheim, Celgene, Clinuvel, Eli Lilly, Incyte, Janssen Research and Development, LLC, Kadmon Corp, LLC, Leo Pharmaceuticals, MedImmune, Novartis, Ortho Dermatologics, Pfizer, Sciderm, UCB, and Vida; and is a consultant for Allergan, Almirall, Arcutis, Inc, Avotres Therapeutics, BirchBioMed Inc, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Foundation for Research and Education in Dermatology, Inozyme Pharma, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy's Laboratories, Theravance, and Verrica. Dr Mabuchi has served as a paid speaker for Eli Lilly, Maruho, Kyowa Kirin, Celgene, and Janssen and has received research funds from Kyowa Kirin, Torii, Maruho, Taiho, and Leo Pharma. Author Leung is an employee of Syneos Health, on behalf of Eli Lilly. Dr Garrelts, Author Crane, Drs ElMaraghy and Patel, Author Ridenour, and Drs See and Gallo are employees of Eli Lilly and Company and own stock. Dr Paul is a consultant and investigator for Amgen, AbbVie, Almirall, Boehringer Ingelheim, Celgene, Dermira, Janssen-Cilag, Leo Pharma, Eli Lilly and Company, GlaxoSmithKline, Novartis, Pfizer, Pierre Fabre, Regeneron, Sanofi Genzyme, and UCB Pharma., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Long-term efficacy, safety, and quality of life with ixekizumab (IXE) through 5 years in UNCOVER-1 and UNCOVER-2 patients with baseline scalp, nail, or palmoplantar psoriasis were assessed., Methods: Patients included in this intent-to-treat subanalysis had baseline involvement in at least one of the three anatomic areas (scalp, fingernail, or palmoplantar locations) and 1) received IXE through week 60, with a 160-mg starting dose 80 mg Q2W through week 12 and Q4W thereafter, 2) achieved a static Physician&rsquo;s Global Assessment score of 0 or 1 at week 12, and 3) completed week 60 and continued treatment with IXE Q4W or were escalated to Q2W during the long-term extension. Efficacy outcomes (e.g., percent improvement in Psoriasis Scalp Severity Index [PSSI], Nail Psoriasis Severity Index [NAPSI], Palmoplantar Psoriasis Area and Severity [PPASI], and Dermatology Life Quality Index [DLQI]) were summarized by descriptive statistics through week 264., Results: Patients rapidly achieved and sustained improvements in scalp, nail, and palmoplantar psoriasis for up to 5 years with IXE. Patients achieved complete clearance at year 5: observed (scalp, 82%; nail, 73%; palmoplantar, 96%) and mNRI (scalp, 77%; nail, 67%; palmoplantar, 85%). Up to 80% of patients reported DLQI 0,1 responses at week 12, which were sustained through week 264. No increases in the number of annual treatment-emergent adverse events were observed from years 1&ndash;5., Conclusion: Patients receiving IXE for 5 years sustained high rates of improvement in scalp, nail, and palmoplantar psoriasis, with a long-term quality of life benefit with no unexpected safety signals. J Drugs Dermatol. 2021;20(8):880-887. doi:10.36849/JDD.6101.

Background: Significantly more patients with moderate-to-severe plaque psoriasis treated with the interleukin (IL)-17A inhibitor ixekizumab vs. the IL-23p19 inhibitor guselkumab in the IXORA-R head-to-head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 12., Objectives: To compare skin and nail clearance and patient-reported outcomes for ixekizumab vs. guselkumab, up to week 24., Methods: IXORA-R enrolled adults with moderate-to-severe plaque psoriasis, defined as static Physician's Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. Statistical comparisons were performed using the Cochran-Mantel-Haenszel test stratified by pooled site. Time-to-first-event comparisons were performed using Kaplan-Meier analysis, and P-values were generated using adjusted log-rank tests stratified by treatment group. Cumulative days at clinical and patient-reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323)., Results: Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 507 guselkumab). As early as week 2 and through week 16, more patients on ixekizumab achieved PASI 100 (P < 0·01). At week 24, ixekizumab was noninferior to guselkumab (50% vs. 52%, difference -2·3%), with no statistically significant difference in PASI 100 (P = 0·41). More patients receiving ixekizumab showed completely clear nails at week 24 (52% vs. 31%, P = 0·007). The median time to first PASI 50/75/90 and PASI 100 were 2 and 7·5 weeks shorter, respectively, for patients on ixekizumab vs. guselkumab (P < 0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, with Dermatology Life Quality Index of 0 or 1, and itch free (P < 0·05). The frequency of serious adverse events was 3% for each group, with no new safety signals., Conclusions: Ixekizumab was noninferior to guselkumab in complete skin clearance and superior in clearing nails at week 24. Ixekizumab cleared skin more rapidly in patients with moderate-to-severe plaque psoriasis, with a greater cumulative benefit, than guselkumab. Overall, the safety findings were consistent with the known safety profile for ixekizumab., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Introduction: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for treatment of moderate-to-severe plaque psoriasis. Our objective was to evaluate the long-term efficacy and safety of ixekizumab in moderate-to-severe plaque psoriasis through 5 years., Methods: Data were integrated from the UNCOVER-1 and UNCOVER-2, randomized, double-blinded, phase-3 trials. Patients who continuously received the labeled ixekizumab dose, were static Physician's Global Assessment (sPGA) (0,1) responders at Week 12 and completed 60 weeks of treatment could enter the long-term extension (LTE) period. Patients could escalate to every-2-week dosing per investigator opinion. Efficacy and health outcomes included proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1) and (0), absolute PASI ≤ 5/ ≤ 3/ ≤ 2/ ≤ 1 and Dermatology Life Quality Index (DLQI) (0,1). Results exclude patients who escalated to every-2-week dosing. A modified non-responder imputation method was used to account for missing data. Supplemental analyses include patients who escalated to every-2-week dosing and observed and multiple imputation results. Exposure-adjusted safety outcomes are also reported., Results: Of 206 patients who entered the LTE periods, 172 completed treatment. At Week 60, PASI 75/90/100 responses were 94.7%, 85.0% and 62.1%, respectively, and at year 5 were 90.3%, 71.3% and 46.3%, respectively. Similarly, meaningful responses were achieved for the other efficacy and health measures. Among patients with PASI 100 through 5 years, 92% achieved DLQI (0,1), indicating no impact of skin disease on quality of life. During the LTE period, exposure-adjusted incidence rates were 31.4 per 100 patient-years for treatment-emergent adverse events and 6.8 per 100 patient-years for serious adverse events. No deaths were reported. No new or unexpected safety findings were noted., Conclusions: The results demonstrate 80 mg ixekizumab maintains long-term efficacy and a safety profile consistent with previous data in patients with moderate-to-severe plaque psoriasis through 5 years of treatment., Trial Registration: ClinicalTrials.gov identifier, UNCOVER-1: NCT01474512, UNCOVER-2: NCT01597245.

Background: Patients with psoriasis value rapid and complete skin clearance. No head-to-head studies have focused on early responses to interleukin (IL)-17 vs. IL-23 inhibitors., Objectives: To compare early and complete skin clearance by the IL-17A inhibitor ixekizumab vs. the IL-23p19 inhibitor guselkumab., Methods: IXORA-R, a 24-week, randomized, double-blinded study, enrolled adults with moderate-to-severe plaque psoriasis [static Physician's Global Assessment of Disease (sPGA) score of ≥ 3, Psoriasis Area and Severity Index (PASI) ≥ 12, and ≥ 10% body surface area]. Patients were randomized (1 : 1) to receive the approved dose of subcutaneous ixekizumab or guselkumab. Primary end point was 100% improvement in PASI (PASI 100) at week 12. Major secondary end points included other levels of improved PASI and sPGA at different time points. Comparisons were made using the Cochran-Mantel-Haenszel test with a multiple testing strategy. Nonresponder imputation was used for missing data. After the completion of the study, the final secondary end point (PASI 100 at 24 weeks) and safety data through week 24 will be reported., Results: In total, 1027 patients were randomized. The primary end point PASI 100 at week 12 was met [215/520 ixekizumab (41%); 126/507 guselkumab (25%); P < 0·001]. All major secondary end points measured up to week 12 were met, including PASI 50 at week 1 and PASI 75 at week 2. Serious adverse event frequency was 3% for each group; no new safety signals were identified., Conclusions: Ixekizumab was superior to guselkumab for rapidly improving signs and symptoms in patients with moderate-to-severe plaque psoriasis by week 12. Adverse events were similar to previous ixekizumab and guselkumab studies. Compared with the IL-23 inhibitor guselkumab, ixekizumab can offer complete skin clearance more rapidly to patients with moderate-to-severe plaque psoriasis. What's already known about this topic? Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, has demonstrated greater and faster skin clearance than etanercept and ustekinumab, with consistent long-term efficacy, safety and durability of response. Clinical trial data and systematic reviews have suggested that IL-17 inhibitors can improve a patient's psoriasis more rapidly than IL-23 inhibitors. What does this study add? The head-to-head study design directly compares the efficacy and speed of response of ixekizumab and the IL-23 inhibitor guselkumab in moderate-to-severe plaque psoriasis. The primary end point was met, showing superiority of ixekizumab over guselkumab for achieving complete skin clearance at week 12. The safety profile of ixekizumab was consistent with previous studies. Ixekizumab can deliver patients complete skin clearance and improved quality of life more rapidly than guselkumab., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Long-term management of moderate-to-severe psoriasis is usually discussed in terms of continuous administration; however, there are many situations in clinical practice where treatment may be withdrawn with subsequent retreatment., Objective: To assess the clinical course after ixekizumab treatment withdrawal and retreatment, as well as the effectiveness of ixekizumab retreatment, in Japanese patients with plaque psoriasis., Methods: This single-arm, open-label study (UNCOVER-J; NCT01624233) comprised 78 patients with plaque psoriasis. After ixekizumab treatment (160-mg loading dose, 80 mg every 2 weeks for the first 12 weeks, and then 80 mg every 4 weeks (IXE Q4W) until Week 52), 70 patients achieved a Psoriasis Area Severity Index (PASI)75 response at Week 52. These 70 patients withdrew from ixekizumab treatment from Weeks 52 to 100. Patients who relapsed (PASI ≤50) during the Treatment Withdrawal Period were retreated with IXE Q4W for 192 weeks., Results: At Weeks 52, 76 and 100, PASI75 response rates were 100%, 26% and 7%; PASI90 response rates were 87%, 11% and 3%; and PASI100 response rates were 53%, 0% and 0%. After treatment withdrawal, 87% of patients relapsed; median time to relapse was 143 days. After 12 weeks of retreatment with IXE Q4W, 83% of relapsed patients achieved PASI75, 68% achieved PASI90 and 25% achieved PASI100; improvements were maintained up to 120 weeks of retreatment. Treatment-emergent adverse events and serious adverse events were reported in 56% and 4% of patients during the Treatment Withdrawal Period, and in 88% and 14% of patients during the Retreatment Period., Conclusion: In patients withdrawn from ixekizumab after achieving PASI75, approximately half relapsed within 5 months of withdrawal; however, most patients recaptured response within 12 weeks, and response was maintained for up to 120 weeks of retreatment., (© 2018 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Erythrodermic and generalized pustular psoriasis are rare, difficult to treat forms of psoriasis. In previous reports, we documented 24- and 52-week findings of an open-label, phase 3 trial (UNCOVER-J) of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis; most patients responded to treatment and maintained response through 52 weeks., Objective: To assess the long-term (>3 years) efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis., Methods: These subgroup analyses were of a partial population of patients from UNCOVER-J (NCT01624233; Sponsored by Eli Lilly and Company), specifically those with erythrodermic psoriasis (N = 8) or generalized pustular psoriasis (N = 5). These patients received 160 mg ixekizumab at Week 0, ixekizumab 80 mg every 2 weeks through Week 12, and ixekizumab 80 mg every 4 weeks thereafter up to Week 244. This regimen is consistent with the regimen approved in Japan for plaque, erythrodermic, and generalized pustular psoriasis and psoriatic arthritis. Efficacy assessments included Global Improvement Score (GIS), Psoriasis Area and Severity Index (PASI), dermal symptoms (for patients with generalized pustular psoriasis), Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS). Safety assessments included treatment-emergent adverse events and adverse events of special interest., Results: Most patients had a GIS of resolved or improved from Week 12 onwards, and all patients had early and sustained improvement in PASI and dermal symptom (generalized pustular psoriasis only) scores. Mean improvements in DLQI and Itch NRS at Week 12 were sustained through Week 244. Ixekizumab was well tolerated over 3 years of treatment in patients with erythrodermic psoriasis or generalized pustular psoriasis, and no new safety concerns were identified., Conclusion: These findings suggest that ixekizumab can be an effective long-term treatment option for erythrodermic or generalized pustular psoriasis., (© 2018 The Author. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Lebrikizumab monotherapy significantly improved signs and symptoms in patients with moderate-to-severe atopic dermatitis (AD) in phase 3 Advocate1 and ADvocate2 studies., Objective: To evaluate improvements in patient-reported symptoms and quality-of-life (QoL) measures by Eczema Area and Severity Index (EASI) response categories using pooled Advocate1 and ADvocate2 data (post hoc analysis)., Methods: In the 52-week (W) (16-W induction + 36-W maintenance) double-blind, placebo-controlled ADvocate1 and ADvocate2 studies, patients were randomized (2:1) to receive subcutaneous lebrikizumab 250 mg or placebo every 2 weeks. Investigator Global Assessment (IGA) 0/1 and improvements in QoL outcomes were assessed at W16 among lebrikizumab-treated patients., Results: At W16, 564 patients were categorized by EASI response (EASI <50: 32.8%; EASI ≥50-<75: 13.8%; EASI ≥75-<90: 20.2%; EASI ≥90: 33.2%). Patients with higher EASI responses showed higher IGA 0/1 response rates (EASI ≥75-<90: 37.7% and EASI ≥90: 86.1%). Pruritus NRS (least squares mean range: -1.5 to -4.4), sleep-loss score (-0.6 to -1.6), and Dermatology Life Quality Index (-3.3 to -10.6) improved across EASI response categories ( p  < 0.001). Anxiety and depression scores improved for most EASI response categories ( p  < 0.01)., Conclusion: Lebrikizumab-treated patients with moderate-to-severe AD showed improved symptoms and QoL across EASI response categories at W16, with greater improvements observed in patients with higher EASI responses.