PMID- 37318750
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230702
IS  - 2193-8210 (Print)
IS  - 2190-9172 (Electronic)
VI  - 13
IP  - 7
DP  - 2023 Jul
TI  - Safety and Efficacy of Lebrikizumab in Adolescent Patients with 
      Moderate-to-Severe Atopic Dermatitis: A 52-Week, Open-Label, Phase 3 Study.
PG  - 1517-1534
LID - 10.1007/s13555-023-00942-y [doi]
AB  - 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.
CI  - (c) 2023. The Author(s).
FAU - Paller, Amy S
AU  - Paller AS
AUID- ORCID: 0000-0001-6187-6549
AD  - Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 
      apaller@northwestern.edu.
FAU - Flohr, Carsten
AU  - Flohr C
AD  - St John's Institute of Dermatology, King's College London, London, UK.
FAU - Eichenfield, Lawrence F
AU  - Eichenfield LF
AD  - University of California, San Diego, USA.
FAU - Irvine, Alan D
AU  - Irvine AD
AD  - Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
FAU - Weisman, Jamie
AU  - Weisman J
AD  - Medical Dermatology Specialists, Atlanta, GA, USA.
FAU - Soung, Jennifer
AU  - Soung J
AD  - Southern California Dermatology, Inc., Santa Ana, CA, USA.
FAU - Pinto Correia, Ana
AU  - Pinto Correia A
AD  - Eli Lilly and Company, Indianapolis, USA.
FAU - Natalie, Chitra R
AU  - Natalie CR
AD  - Eli Lilly and Company, Indianapolis, USA.
FAU - Rodriguez Capriles, Claudia
AU  - Rodriguez Capriles C
AD  - Eli Lilly and Company, Indianapolis, USA.
FAU - Pierce, Evangeline
AU  - Pierce E
AD  - Eli Lilly and Company, Indianapolis, USA.
FAU - Reifeis, Sarah
AU  - Reifeis S
AD  - Eli Lilly and Company, Indianapolis, USA.
FAU - Gontijo Lima, Renata
AU  - Gontijo Lima R
AD  - Eli Lilly and Company, Indianapolis, USA.
FAU - Armengol Tubau, Clara
AU  - Armengol Tubau C
AD  - Almirall S.A., Barcelona, Spain.
FAU - Laquer, Vivian
AU  - Laquer V
AD  - First OC Dermatology Research, California, USA.
FAU - Weidinger, Stephan
AU  - Weidinger S
AD  - Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, 
      Kiel, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT04250350
PT  - Journal Article
DEP - 20230615
PL  - Switzerland
TA  - Dermatol Ther (Heidelb)
JT  - Dermatology and therapy
JID - 101590450
PMC - PMC10307734
OAB - 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).
OABL- eng
OTO - NOTNLM
OT  - Adolescents
OT  - Efficacy
OT  - IL-13
OT  - Lebrikizumab
OT  - Moderate-to-severe atopic dermatitis
OT  - Safety
COIS- 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.
EDAT- 2023/06/15 13:07
MHDA- 2023/06/15 13:08
PMCR- 2023/06/15
CRDT- 2023/06/15 11:16
PHST- 2023/03/15 00:00 [received]
PHST- 2023/05/17 00:00 [accepted]
PHST- 2023/06/15 13:08 [medline]
PHST- 2023/06/15 13:07 [pubmed]
PHST- 2023/06/15 11:16 [entrez]
PHST- 2023/06/15 00:00 [pmc-release]
AID - 10.1007/s13555-023-00942-y [pii]
AID - 942 [pii]
AID - 10.1007/s13555-023-00942-y [doi]
PST - ppublish
SO  - Dermatol Ther (Heidelb). 2023 Jul;13(7):1517-1534. doi: 
      10.1007/s13555-023-00942-y. Epub 2023 Jun 15.