Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis

Jonathan I. Silverberg, From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.); the Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany (D.T.); the Department of Clinical Medicine, Trinity College Dublin, Dublin (A.D.I.); Dermatology Clinical Research, Henry Ford Health System, Detroit (L.S.G.); Oregon Medical Research Center (A.B.), and the Department of Dermatology, Oregon Health and Science University (E.L.S.) - both in Portland; the Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei (C.-Y.C.); Eli Lilly, Indianapolis (Z.L., R.G.L., S.G.P.); and the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hospital Saint-André, Bordeaux University, Centre National de la Recherche Scientifique, ImmunoConcept, Unité Mixte de Recherche 5164, Bordeaux, France (J.S.).
Emma Guttman-Yassky, From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.); the Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany (D.T.); the Department of Clinical Medicine, Trinity College Dublin, Dublin (A.D.I.); Dermatology Clinical Research, Henry Ford Health System, Detroit (L.S.G.); Oregon Medical Research Center (A.B.), and the Department of Dermatology, Oregon Health and Science University (E.L.S.) - both in Portland; the Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei (C.-Y.C.); Eli Lilly, Indianapolis (Z.L., R.G.L., S.G.P.); and the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hospital Saint-André, Bordeaux University, Centre National de la Recherche Scientifique, ImmunoConcept, Unité Mixte de Recherche 5164, Bordeaux, France (J.S.).
Diamant Thaçi, From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.); the Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany (D.T.); the Department of Clinical Medicine, Trinity College Dublin, Dublin (A.D.I.); Dermatology Clinical Research, Henry Ford Health System, Detroit (L.S.G.); Oregon Medical Research Center (A.B.), and the Department of Dermatology, Oregon Health and Science University (E.L.S.) - both in Portland; the Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei (C.-Y.C.); Eli Lilly, Indianapolis (Z.L., R.G.L., S.G.P.); and the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hospital Saint-André, Bordeaux University, Centre National de la Recherche Scientifique, ImmunoConcept, Unité Mixte de Recherche 5164, Bordeaux, France (J.S.).
Alan D. Irvine, From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.); the Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany (D.T.); the Department of Clinical Medicine, Trinity College Dublin, Dublin (A.D.I.); Dermatology Clinical Research, Henry Ford Health System, Detroit (L.S.G.); Oregon Medical Research Center (A.B.), and the Department of Dermatology, Oregon Health and Science University (E.L.S.) - both in Portland; the Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei (C.-Y.C.); Eli Lilly, Indianapolis (Z.L., R.G.L., S.G.P.); and the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hospital Saint-André, Bordeaux University, Centre National de la Recherche Scientifique, ImmunoConcept, Unité Mixte de Recherche 5164, Bordeaux, France (J.S.).
Linda Stein Gold, From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.); the Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany (D.T.); the Department of Clinical Medicine, Trinity College Dublin, Dublin (A.D.I.); Dermatology Clinical Research, Henry Ford Health System, Detroit (L.S.G.); Oregon Medical Research Center (A.B.), and the Department of Dermatology, Oregon Health and Science University (E.L.S.) - both in Portland; the Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei (C.-Y.C.); Eli Lilly, Indianapolis (Z.L., R.G.L., S.G.P.); and the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hospital Saint-André, Bordeaux University, Centre National de la Recherche Scientifique, ImmunoConcept, Unité Mixte de Recherche 5164, Bordeaux, France (J.S.).
Andrew Blauvelt, From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.); the Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany (D.T.); the Department of Clinical Medicine, Trinity College Dublin, Dublin (A.D.I.); Dermatology Clinical Research, Henry Ford Health System, Detroit (L.S.G.); Oregon Medical Research Center (A.B.), and the Department of Dermatology, Oregon Health and Science University (E.L.S.) - both in Portland; the Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei (C.-Y.C.); Eli Lilly, Indianapolis (Z.L., R.G.L., S.G.P.); and the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hospital Saint-André, Bordeaux University, Centre National de la Recherche Scientifique, ImmunoConcept, Unité Mixte de Recherche 5164, Bordeaux, France (J.S.).
Eric L. Simpson, From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.); the Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany (D.T.); the Department of Clinical Medicine, Trinity College Dublin, Dublin (A.D.I.); Dermatology Clinical Research, Henry Ford Health System, Detroit (L.S.G.); Oregon Medical Research Center (A.B.), and the Department of Dermatology, Oregon Health and Science University (E.L.S.) - both in Portland; the Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei (C.-Y.C.); Eli Lilly, Indianapolis (Z.L., R.G.L., S.G.P.); and the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hospital Saint-André, Bordeaux University, Centre National de la Recherche Scientifique, ImmunoConcept, Unité Mixte de Recherche 5164, Bordeaux, France (J.S.).
Chia-Yu Chu, From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.); the Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany (D.T.); the Department of Clinical Medicine, Trinity College Dublin, Dublin (A.D.I.); Dermatology Clinical Research, Henry Ford Health System, Detroit (L.S.G.); Oregon Medical Research Center (A.B.), and the Department of Dermatology, Oregon Health and Science University (E.L.S.) - both in Portland; the Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei (C.-Y.C.); Eli Lilly, Indianapolis (Z.L., R.G.L., S.G.P.); and the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hospital Saint-André, Bordeaux University, Centre National de la Recherche Scientifique, ImmunoConcept, Unité Mixte de Recherche 5164, Bordeaux, France (J.S.).
Zhuqing Liu, From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.); the Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany (D.T.); the Department of Clinical Medicine, Trinity College Dublin, Dublin (A.D.I.); Dermatology Clinical Research, Henry Ford Health System, Detroit (L.S.G.); Oregon Medical Research Center (A.B.), and the Department of Dermatology, Oregon Health and Science University (E.L.S.) - both in Portland; the Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei (C.-Y.C.); Eli Lilly, Indianapolis (Z.L., R.G.L., S.G.P.); and the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hospital Saint-André, Bordeaux University, Centre National de la Recherche Scientifique, ImmunoConcept, Unité Mixte de Recherche 5164, Bordeaux, France (J.S.).
Renata Gontijo Lima, From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.); the Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany (D.T.); the Department of Clinical Medicine, Trinity College Dublin, Dublin (A.D.I.); Dermatology Clinical Research, Henry Ford Health System, Detroit (L.S.G.); Oregon Medical Research Center (A.B.), and the Department of Dermatology, Oregon Health and Science University (E.L.S.) - both in Portland; the Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei (C.-Y.C.); Eli Lilly, Indianapolis (Z.L., R.G.L., S.G.P.); and the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hospital Saint-André, Bordeaux University, Centre National de la Recherche Scientifique, ImmunoConcept, Unité Mixte de Recherche 5164, Bordeaux, France (J.S.).
Sreekumar G. Pillai, From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.); the Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany (D.T.); the Department of Clinical Medicine, Trinity College Dublin, Dublin (A.D.I.); Dermatology Clinical Research, Henry Ford Health System, Detroit (L.S.G.); Oregon Medical Research Center (A.B.), and the Department of Dermatology, Oregon Health and Science University (E.L.S.) - both in Portland; the Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei (C.-Y.C.); Eli Lilly, Indianapolis (Z.L., R.G.L., S.G.P.); and the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hospital Saint-André, Bordeaux University, Centre National de la Recherche Scientifique, ImmunoConcept, Unité Mixte de Recherche 5164, Bordeaux, France (J.S.).
Julien Seneschal, From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.); the Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany (D.T.); the Department of Clinical Medicine, Trinity College Dublin, Dublin (A.D.I.); Dermatology Clinical Research, Henry Ford Health System, Detroit (L.S.G.); Oregon Medical Research Center (A.B.), and the Department of Dermatology, Oregon Health and Science University (E.L.S.) - both in Portland; the Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei (C.-Y.C.); Eli Lilly, Indianapolis (Z.L., R.G.L., S.G.P.); and the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hospital Saint-André, Bordeaux University, Centre National de la Recherche Scientifique, ImmunoConcept, Unité Mixte de Recherche 5164, Bordeaux, France (J.S.).

Document Type

Journal Article

Publication Date

3-23-2023

Journal

The New England journal of medicine

Volume

388

Issue

12

DOI

10.1056/NEJMoa2206714

Abstract

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: 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: 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: 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.).

Department

Dermatology

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