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. 2023 Jul;13(7):1517-1534.
doi: 10.1007/s13555-023-00942-y. Epub 2023 Jun 15.

Safety and Efficacy of Lebrikizumab in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis: A 52-Week, Open-Label, Phase 3 Study

Amy S Paller  1 , Carsten Flohr  2 , Lawrence F Eichenfield  3 , Alan D Irvine  4 , Jamie Weisman  5 , Jennifer Soung  6 , Ana Pinto Correia  7 , Chitra R Natalie  7 , Claudia Rodriguez Capriles  7 , Evangeline Pierce  7 , Sarah Reifeis  7 , Renata Gontijo Lima  7 , Clara Armengol Tubau  8 , Vivian Laquer  9 , Stephan Weidinger  10
Affiliations

Safety and Efficacy of Lebrikizumab in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis: A 52-Week, Open-Label, Phase 3 Study

Amy S Paller et al. Dermatol Ther (Heidelb). 2023 Jul.

Abstract

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.

Keywords: Adolescents; Efficacy; IL-13; Lebrikizumab; Moderate-to-severe atopic dermatitis; Safety.

Plain language summary

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. 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).

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Conflict of interest statement

Amy S. Paller is a consultant with honorarium from AbbVie, Acrotech, Almirall, Amgen, Amryt, Arcutis, Arena, Azitra, BioCryst, BiomX, Boeringer Ingelheim, Botanix, Bridgebio, Castle Biosciences, Catawba, Eli Lilly and Company, Exicure, Gilead, Incyte, Janssen, Kamari, LEO Pharma, Novartis, Pfizer, Pierre Fabre, RAPT, Regeneron, Sanofi/Genzyme, Seanergy, UCB, and Union. She is an investigator for AbbVie, AnaptysBio, Dermavant, Eli Lilly and Company, Incyte, Janssen, Krystal, Regeneron, and UCB. She is on the Data Safety Monitoring Board for AbbVie, Abeona, Bausch, Bristol Myers Squibb, Galderma, Inmed, and Novan. Carsten Flohr is Chief Investigator of the UK National Institute for Health Research-funded TREAT (ISRCTN15837754) and SOFTER (Clinicaltrials.gov: NCT03270566) trials as well as the UK-Irish Atopic eczema Systemic Therapy Register (A-STAR; ISRCTN11210918) and a Principal Investigator in the European Union (EU) Horizon 2020-funded BIOMAP Consortium (http://www.biomap-imi.eu/). He also leads the EU Horizon 2020 Joint Program Initiative-funded Trans-Foods consortium. His department has received funding from Sanofi Genzyme and Pfizer for skin microbiome work. Lawrence F. Eichenfield has been a consultant/advisory board member, speaker, and/or has served as an investigator for Amgen, AbbVie, Arcutis, Aslan, Bausch, Castle Biosciences, Dermavant, Eli Lilly and Company, Forte, Galderma, Incyte, Janssen, Novartis, Otsuka, Pfizer, Regeneron, Sanofi Genzyme, Seanergy, and UCB. Alan D. Irvine is a consultant/advisory board member/DSMB for AbbVie, Novartis, Regeneron, Sanofi, Pfizer, Eli Lilly and Company, Benevolent AI, LEO Pharma, and Arena. He has received research grants from AbbVie and Pfizer; is on the board of directors of the International Eczema Council; provides research support to Regeneron; and is in the speakers bureau for AbbVie, Regeneron, Sanofi Genzyme, and Eli Lilly and Company. Jamie Weisman is an advisory board member for Sanofi, Regeneron, UCB, Eli Lilly and Company, and Novartis. She has received speaking fees from Eli Lilly and Company, Sanofi, Regeneron, and AbbVie and research grants from AbbVie, Aclaris, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Dermavent, Glaxo Smith Kline, Incyte, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, and UCB. Jennifer Soung has received speaker honoraria from AbbVie, Actelion, Amgen, Celgene, Dermira, Eli Lilly and Company, National Psoriasis Foundation, Novartis, Ortho Dermatologics, and Regeneron; consulting/advisory board honoraria from LEO Pharma, Lilly, and Novartis; and grant/research grant funding from AbbVie, Actavis, Actelion, Allergan, Boehringer Ingelheim, Cassiopea, Dr Reddy’s, Galderma, Glaxo Smith Kline, Janssen, Kadmon, Kyowa Kirin, LEO Pharma, Menlo, Novan, Novartis, Ortho Dermatologics, Pfizer, and UCB. Ana Pinto Correia was a full-time employee of Eli Lilly and Company at the time of the study and authoring of the manuscript. She is now a full-time employee of Glaxo Smith Kline; Chitra R. Natalie, Claudia Rodriguez Capriles, Evangeline Pierce, Sarah Reifeis, and Renata Gontijo Lima are full-time employees and stockholders of Eli Lilly and Company. Clara Armengol Tubau is a full-time employee of Almirall. Vivian Laquer is consultant with honorarium from Eli Lilly and Company, Galderma, and Cara. She is investigator for AbbVie, Amgen, Anaptys Bio, Arcutis, Argenx, Aslan, Biofrontera, Bristol Meyers Squibb, Castle, Dermavant, Eli Lilly and Company, Galderma, Incyte, Janssen Research & Development, Kiniksa, LEO Pharma, Moonlake, Novartis, Pfizer, Rapt Therapeutics, Sun Pharma, and UCB. Stephan Weidinger is a speaker, advisory board member, and/or investigator for AbbVie, Almirall, Galderma, Kymab, LEO Pharma, Eli Lilly and Company, Pfizer, Regeneron, and Sanofi. He has received research grants from Sanofi, Pfizer, LEO Pharma, and La Roche Posay.

Figures

Fig. 1
Fig. 1
CONSORT diagram outlining patient disposition, including patient numbers assessed for eligibility (N = 245), excluded (N = 39), enrolled (N = 206), discontinued treatment (N = 34), and completed treatment (N = 172)
Fig. 2
Fig. 2
Time course response for EASI clinical outcomes. Percentage of patients (%) achieving EASI-75 (A), EASI-90 (B), EASI-50 (C), and EASI percentage change from baseline (D) through 52 weeks. Missing data due to lack of efficacy were imputed with non-responder imputation. Other missing data were imputed with multiple imputation. Abbreviations: EASI Eczema Area and Severity Index, EASI-50 50% reduction in EASI, EASI-75 75% reduction in EASI, EASI-90 90% reduction in EASI, LEBRI lebrikizumab, Q2W every 2 weeks
Fig. 3
Fig. 3
Time course response for IGA (0,1) with ≥ 2-point reduction from baseline. Percentage of patients (%) with IGA 0,1 and ≥ 2-point reduction from baseline through 52 weeks. A total of 62.6% of patients (N = 129) achieved IGA 0 or 1 with ≥ 2-point reduction from baseline at Week 52. Missing data due to lack of efficacy were imputed with non-responder imputation. Other missing data were imputed with multiple imputation. Abbreviations: IGA Investigator’s Global Assessment, LEBRI lebrikizumab, Q2W every 2 weeks
Fig. 4
Fig. 4
Time course response for BSA mean change from baseline. Mean change from baseline in BSA score. Data presented as observed value by visit. Abbreviations: BSA Body Surface Area, LEBRI lebrikizumab, Q2W every 2 weeks
Fig. 5
Fig. 5
Mean change from baseline in DLQI (A) and CDLQI (B) scores. Missing data due to lack of efficacy were imputed with non-responder imputation. Other missing data were imputed with multiple imputation. Abbreviations: CDLQI Children’s Dermatology Life Quality Index, DLQI Dermatology Life Quality Index, LEBRI lebrikizumab, Q2W every 2 weeks
Fig. 6
Fig. 6
Mean change from baseline in PROMIS Anxiety (A) and PROMIS Depression (B) scores. Data presented as the as-observed analyses. Abbreviation: PROMIS patient-reported outcomes measurement information system
See this image and copyright information in PMC

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