Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis.
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
23 Mar 2023
23 Mar 2023
Historique:
pubmed:
16
3
2023
medline:
25
3
2023
entrez:
15
3
2023
Statut:
ppublish
Résumé
Lebrikizumab, a high-affinity IgG4 monoclonal antibody targeting interleukin-13, prevents the formation of the interleukin-4Rα-interleukin-13Rα1 heterodimer receptor signaling complex. We conducted two identically designed, 52-week, randomized, double-blind, placebo-controlled, phase 3 trials; both trials included a 16-week induction period and a 36-week maintenance period. Eligible patients with moderate-to-severe atopic dermatitis (adults [≥18 years of age] and adolescents [12 to <18 years of age, weighing ≥40 kg]) were randomly assigned in a 2:1 ratio to receive either lebrikizumab at a dose of 250 mg (loading dose of 500 mg at baseline and week 2) or placebo, administered subcutaneously every 2 weeks. Outcomes for the induction period were assessed up to 16 weeks and are included in this report. The primary outcome was an Investigator's Global Assessment (IGA) score of 0 or 1 (indicating clear or almost clear skin; range, 0 to 4 [severe disease]) with a reduction (indicating improvement) of at least 2 points from baseline at week 16. Secondary outcomes included a 75% improvement in the Eczema Area and Severity Index score (EASI-75 response) and assessments of itch and of itch interference with sleep. Safety was also assessed. In trial 1, the primary outcome was met in 43.1% of 283 patients in the lebrikizumab group and in 12.7% of 141 patients in the placebo group (P<0.001); an EASI-75 response occurred in 58.8% and 16.2%, respectively (P<0.001). In trial 2, the primary outcome was met in 33.2% of 281 patients in the lebrikizumab group and in 10.8% of 146 patients in the placebo group (P<0.001); an EASI-75 response occurred in 52.1% and 18.1%, respectively (P<0.001). Measures of itch and itch interference with sleep indicated improvement with lebrikizumab therapy. The incidence of conjunctivitis was higher among patients who received lebrikizumab than among those who received placebo. Most adverse events during the induction period were mild or moderate in severity and did not lead to trial discontinuation. In the induction period of two phase 3 trials, 16 weeks of treatment with lebrikizumab was effective in adolescents and adults with moderate-to-severe atopic dermatitis. (Funded by Dermira; ADvocate1 and ADvocate2 ClinicalTrials.gov numbers, NCT04146363 and NCT04178967, respectively.).
Sections du résumé
BACKGROUND
BACKGROUND
Lebrikizumab, a high-affinity IgG4 monoclonal antibody targeting interleukin-13, prevents the formation of the interleukin-4Rα-interleukin-13Rα1 heterodimer receptor signaling complex.
METHODS
METHODS
We conducted two identically designed, 52-week, randomized, double-blind, placebo-controlled, phase 3 trials; both trials included a 16-week induction period and a 36-week maintenance period. Eligible patients with moderate-to-severe atopic dermatitis (adults [≥18 years of age] and adolescents [12 to <18 years of age, weighing ≥40 kg]) were randomly assigned in a 2:1 ratio to receive either lebrikizumab at a dose of 250 mg (loading dose of 500 mg at baseline and week 2) or placebo, administered subcutaneously every 2 weeks. Outcomes for the induction period were assessed up to 16 weeks and are included in this report. The primary outcome was an Investigator's Global Assessment (IGA) score of 0 or 1 (indicating clear or almost clear skin; range, 0 to 4 [severe disease]) with a reduction (indicating improvement) of at least 2 points from baseline at week 16. Secondary outcomes included a 75% improvement in the Eczema Area and Severity Index score (EASI-75 response) and assessments of itch and of itch interference with sleep. Safety was also assessed.
RESULTS
RESULTS
In trial 1, the primary outcome was met in 43.1% of 283 patients in the lebrikizumab group and in 12.7% of 141 patients in the placebo group (P<0.001); an EASI-75 response occurred in 58.8% and 16.2%, respectively (P<0.001). In trial 2, the primary outcome was met in 33.2% of 281 patients in the lebrikizumab group and in 10.8% of 146 patients in the placebo group (P<0.001); an EASI-75 response occurred in 52.1% and 18.1%, respectively (P<0.001). Measures of itch and itch interference with sleep indicated improvement with lebrikizumab therapy. The incidence of conjunctivitis was higher among patients who received lebrikizumab than among those who received placebo. Most adverse events during the induction period were mild or moderate in severity and did not lead to trial discontinuation.
CONCLUSIONS
CONCLUSIONS
In the induction period of two phase 3 trials, 16 weeks of treatment with lebrikizumab was effective in adolescents and adults with moderate-to-severe atopic dermatitis. (Funded by Dermira; ADvocate1 and ADvocate2 ClinicalTrials.gov numbers, NCT04146363 and NCT04178967, respectively.).
Identifiants
pubmed: 36920778
doi: 10.1056/NEJMoa2206714
doi:
Substances chimiques
Antibodies, Monoclonal
0
Interleukin-13
0
lebrikizumab
U9JLP7V031
Immunoglobulin G
0
Banques de données
ClinicalTrials.gov
['NCT04146363', 'NCT04178967']
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase III
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1080-1091Investigateurs
Rodney Sinclair
(R)
Michael Freeman
(M)
Louise Murdoch
(L)
Lynda Spelman
(L)
Kurt Gebauer
(K)
Ernest Tan
(E)
Peter Foley
(P)
Stephen Shumack
(S)
Johannes Kern
(J)
Jessie Lee
(J)
Ebrahim Abdulla
(E)
Michael Robern
(M)
Mani Raman
(M)
Isaiah Day
(I)
Melinda Gooderham
(M)
David Adam
(D)
Airi Poder
(A)
Mireille Ruer-Mulard
(M)
Carle Paul
(C)
Jean-David Bouaziz
(JD)
Silvestrs Rubins
(S)
Aija Smite
(A)
Ingmars Mikazans
(I)
Diana Viba
(D)
Redzinaldas Narbutas
(R)
Nemira Vaiciulioniene
(N)
Jurate Grigaitiene
(J)
Brigita Sitkauskiene
(B)
Odilija Rudzeviciene
(O)
Laura Malinauskiene
(L)
Jurate Staikuniene-Kozonis
(J)
Magdalena Kolanko
(M)
Adam Reich
(A)
Marcin Zakrzewski
(M)
Anna Rajchel
(A)
Andrzej Langner
(A)
Grazyna Pulka
(G)
Kamila Padlewska
(K)
Bernadetta Majorek-Olechowska
(B)
Tadeusz Debniak
(T)
Barbara Rewerska
(B)
Irena Walecka-Herniczek
(I)
Teresa Hofman
(T)
Jacek Szepietowski
(J)
Pablo De la Cueva
(P)
Juan Salvador
(J)
Rosa Belloso
(R)
Eulalia Torres
(E)
Jose Carrillo
(J)
Esther Serra-Baldrich
(E)
Sang Wook Son
(SW)
Tae-Gyun Kim
(TG)
Chang Ook Park
(CO)
Chong-Hyun Won
(CH)
Moon-Bum Kim
(MB)
Chun Wook Park
(CW)
Beom Joon Kim
(BJ)
Young-Lip Park
(YL)
Dong-Ho Nahm
(DH)
Sang Hyun Cho
(SH)
Joo Yeon Ko
(JY)
Young Suck Ro
(YS)
Yangwon Lee
(Y)
Andrew Blauvelt
(A)
Leon Kircik
(L)
Abel Jarell
(A)
Scott Guenthner
(S)
Gretel Trullenque
(G)
Victoria Kuohung
(V)
Emma Guttman-Yassky
(E)
Francis Averill
(F)
Seth Forman
(S)
Neil Sadick
(N)
Iftikhar Hussain
(I)
William Werschler
(W)
Paul Wallace
(P)
Vivian Laquer
(V)
Melody Stone
(M)
Mark Lee
(M)
Jeffrey Kingsley
(J)
William Paull
(W)
James Del Rosso
(J)
Adnan Nasir
(A)
Sandra Johnson
(S)
Mirwais Saifi
(M)
John Delgado
(J)
Gregg Lucksinger
(G)
Kevin Parks
(K)
Edward Kerwin
(E)
Linda Gold
(L)
Howard Sofen
(H)
Mona Shahriari
(M)
Vassilios Dimitropoulos
(V)
Stacy Smith
(S)
Kathleen Gordon
(K)
Ellen Frankel
(E)
Craig Teller
(C)
Kristina Milkova
(K)
Antoaneta Grunova
(A)
Irida Vasileva
(I)
Vessel Kantardjiev
(V)
Steliyana Kraeva
(S)
Mariela Hitova
(M)
Snejina Vassileva
(S)
Firouzeh Niakosari
(F)
Chih-Ho Hong
(CH)
William Yang
(W)
Maryam Alam
(M)
Kim Papp
(K)
Charles Lynde
(C)
Marc Radtke
(M)
Helena Sigal
(H)
Jana Nikula
(J)
Maria Lehertz
(M)
Diamant Thaci
(D)
Margrit Simon
(M)
Margitta Worm
(M)
Peter Radny
(P)
Andreas Pinter
(A)
Virgil-Oreste Mihaescu
(VO)
Sylvia Pauser
(S)
Thomas Wildfeuer
(T)
Beate Schwarz
(B)
Oliver Weirich
(O)
Christian Termeer
(C)
Georg Popp
(G)
Athanasios Tsianakas
(A)
Nina Magnolo
(N)
Kristian Reich
(K)
Johannes Niesmann
(J)
Jan Simon
(J)
Eduardo Vazquez
(E)
Luis Gonzalez
(L)
Yik Weng Yew
(YW)
Nisha Chandran
(N)
Mark Koh
(M)
Haur Yueh Lee
(HY)
Wen-Hung Chung
(WH)
Chih-Hung Lee
(CH)
Chia-Yu Chu
(CY)
Cheng-Chung Wei
(CC)
Po-Yuan Wu
(PY)
Cheng-Che Lan
(CC)
Woan-Ruoh Lee
(WR)
Nataliya Reznichenko
(N)
Yuriy Andrashko
(Y)
Nataliya Manyak
(N)
Sunil Dhawan
(S)
David Greenstein
(D)
Edward Lain
(E)
Catherine Pointon
(C)
Angela Moore
(A)
Mark Knautz
(M)
Todd Schlesinger
(T)
Mark McCune
(M)
Pearl Kwong
(P)
Jeffrey Weinberg
(J)
Stephen Schleicher
(S)
Rosalyn George
(R)
Bruce Torkan
(B)
David Pariser
(D)
Jose Mendez
(J)
Peter Jenkin
(P)
Scott Gottlieb
(S)
James Moretti
(J)
Swapnil Vaidya
(S)
Wendy McFalda
(W)
Anais Badia
(A)
Jeffrey Crowley
(J)
Michael Heffernan
(M)
Nicole Harrell
(N)
Tracy Bridges
(T)
David Rosmarin
(D)
Jamie Weisman
(J)
Steven Kempers
(S)
Jamie Rhoads
(J)
Jose Carpio
(J)
Michael Bukhalo
(M)
Walter Nahm
(W)
Theresa Knoepp
(T)
Joel Joyce
(J)
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