• Marcus Maurer, Ana M Giménez-Arnau, Gordon Sussman, Martin Metz, Diane R Baker, Andrea Bauer, Jonathan A Bernstein, Randolf Brehler, Chia-Yu Chu, Wen-Hung Chung, Inna Danilycheva, Clive Grattan, Jacques Hébert, Constance Katelaris, Michael Makris, Raisa Meshkova, Sinisa Savic, Rodney Sinclair, Karl Sitz, Petra Staubach, Bettina Wedi, Jürgen Löffler, Avantika Barve, Kenneth Kobayashi, Eva Hua, Thomas Severin, and Reinhold Janocha.
• From the Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin (M. Maurer, M. Metz), the Department of Dermatology, University Allergy Center, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden (A. Bauer), the Department of Dermatology, University Hospital Münster, Münster (R.B.), the Department of Dermatology, University Medical Center Mainz, Mainz (P.S.), and the Department of Dermatology and Allergy, Comprehensive Allergy Center, Hannover Medical School, Hannover (B.W.) - all in Germany; the Dermatology Department, Hospital del Mar-Institut Hospital del Mar d'Investigacions Mèdiques, Universitat Autònoma Barcelona, Barcelona (A.M.G.-A.); the Division of Allergy and Clinical Immunology, St. Michael's Hospital and University of Toronto, Toronto (G.S.), Service d'Allergie, Centre Hospitalier Université Laval-Centre Hospitalier Universitaire de Québec, Quebec, QC (J.H.), and the Department of Medicine, University of Ottawa, Ottawa (K.K.) - all in Canada; Baker Allergy Asthma and Dermatology Clinic, Portland, OR (D.R.B.); University of Cincinnati College of Medicine, Department of Internal Medicine, Division of Immunology, Rheumatology, and Allergy and Bernstein Clinical Research Center, Cincinnati (J.A.B.); the Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine (C.-Y.C.), and the Department of Dermatology, Chang Gung Memorial Hospital (W.-H.C.), Taipei, Taiwan; the National Research Center-Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow (I.D.), and the Department of Clinical Immunology and Allergology, Smolensk State Medical University, Smolensk (R.M.) - both in Russia; St. John's Institute of Dermatology, Guy's and St. Thomas' Hospitals NHS Foundation Trust, London (C.G.), and the National Institute for Health Research-Leeds Biomedical Research Centre and Leeds Institute of Rheumatic and Musculoskeletal Medicine, and the Department of Clinical Immunology and Allergy, St. James's University Hospital, Leeds (S.S.) - all in the United Kingdom; the School of Medicine, Western Sydney University, and the Immunology and Allergy Unit, Campbelltown Hospital, Campbelltown, NSW (C.K.), and Sinclair Dermatology and the Epworth Hospital, Melbourne, VIC (R.S.) - all in Australia; the Second Department of Dermatology and Venereology, Attikon University Hospital, Athens (M. Makris); Little Rock Allergy and Asthma Clinic, Little Rock, AR (K.S.); Novartis Pharma, Basel, Switzerland (J.L., T.S., R.J.); Novartis Pharmaceuticals, East Hanover, NJ (A. Barve, K.K.); and Shanghai Novartis Trading, Shanghai, China (E.H.).
• N. Engl. J. Med. 2019 Oct 3; 381 (14): 1321-1332.

BackgroundIn the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose-response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H1-antihistamines at approved or increased doses, alone or in combination with H2-antihistamines or leukotriene-receptor antagonists.MethodsIn a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose-response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial.ResultsA total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose-response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged.ConclusionsA higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332.).Copyright © 2019 Massachusetts Medical Society.

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