Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials,The Lancet

当前位置： X-MOL 学术 › Lancet › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials
The Lancet ( IF 168.9 ) Pub Date : 2023-11-23 , DOI: 10.1016/s0140-6736(23)01684-7
Marcus Maurer ₁ , Luis Felipe Ensina ₂ , Ana Maria Gimenez-Arnau ₃ , Gordon Sussman ₄ , Michihiro Hide ₅ , Sarbjit Saini ₆ , Clive Grattan ₇ , Daria Fomina ₈ , Dimitrios Rigopoulos ₉ , Frederic Berard ₁₀ , Giorgio Walter Canonica ₁₁ , Heike Rockmann ₁₂ , Carla Irani ₁₃ , Jacek C Szepietowski ₁₄ , Jeffrey Leflein ₁₅ , Jonathan A Bernstein ₁₆ , Jonny G Peter ₁₇ , Kanokvalai Kulthanan ₁₈ , Kiran Godse ₁₉ , Ledit Ardusso ₂₀ , Olga Ukhanova ₂₁ , Petra Staubach ₂₂ , Rodney Sinclair ₂₃ , Shaila Gogate ₂₄ , Simon Francis Thomsen ₂₅ , Tonny Tanus ₂₆ , Young Min Ye ₂₇ , Alis Burciu ₂₈ , Avantika Barve ₂₉ , Darshna Modi ₂₉ , Emil Scosyrev ₂₉ , Eva Hua ₃₀ , Kerstin Letzelter ₂₈ , Vineeth Varanasi ₃₁ , Manmath Patekar ₂₈ , Thomas Severin ₂₈ ,

Affiliation

Urticaria Center of Reference and Excellence (UCARE), Institute of Allergology, Charité-Universitätsmedizin Berlin, Germany; Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany.
Federal University of São Paulo, São Paulo, Brazil; CPAlpha Clinical Research Center, Barueri, Brazil.
Department of Dermatology, Hospital del Mar-IMIM, Universitat Pompeu Fabra, Barcelona, Spain.
Division of Allergy and Clinical Immunology, University of Toronto, Canada.
Department of Dermatology, Hiroshima University, Hiroshima, Japan; Department of Dermatology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan.
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland, MD, USA.
St John's Institute of Dermatology, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK.
Center of Allergy and Immunology, Clinical State Hospital 52, Moscow Ministry of Healthcare, Moscow, Russia; Department of Clinical Allergology and Immunology, I M Sechenov First Moscow State Medical University, Moscow, Russia.
A Sygros University Hospital of Venereal and Skin Diseases, Athens, Greece.
Département d'Allergologie et Immunologie Clinique, CHU Lyon-Sud, Pierre Bénite Cedex, France.
Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy; Department of Biomedical Science, Humanitas University-Pieve Emanuele, Milan, Italy.
Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Internal Medicine and Clinical Immunology, Saint Joseph University, Beirut, Lebanon.
Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland.
Allergy and Immunology Associates of Ann Arbor, PC Ann Arbor, Michigan, MI, USA.
University of Cincinnati College of Medicine Division of Rheumatology, Allergy, and Immunology and Bernstein Clinical Research Center, Cincinnati, OH, USA.
Division of Allergology and Clinical Immunology, Department of Medicine, University of Cape Town, Cape Town, South Africa; Allergy and Immunology Unit, University of Cape Town Lung Institute, Cape Town, South Africa.
Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Department of Dermatology, D Y Patil School of Medicine, Navi Mumbai, Maharashtra, India.
Department of Pulmonology, Allergy and Immunology, School of Medicine, National University of Rosario, Rosario, Santa Fe, Argentina.
Scientific Medical Center of General Therapy and Pharmacology, Stavropol, Russia.
Department of Dermatology, University Medical Center, Mainz, Germany.
Department of Dermatology, St Vincent's Hospital, The Skin and Cancer Foundation of Victoria and The University of Melbourne, Victoria, VIC, Australia.
Colorado Allergy and Asthma Centers, Denver, Colorado, CO, USA.
Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Biomedical Sciences, Copenhagen, Denmark.
Kern Allergy Medical Clinic, Bakersfield, CA, USA.
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
Novartis Pharma, Basel, Switzerland.
Novartis Pharmaceuticals, East Hanover, New Jersey, NJ, USA.
China Novartis Institutes for Biomedical Research, Shanghai, China.
Novartis Healthcare Private, Hyderabad, India.

Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies. PEARL-1 and PEARL-2 were identically designed randomised, double-blind, active-controlled and placebo-controlled parallel-group studies. Patients aged 12 years or older with moderate-to-severe H1-AH refractory CSU were recruited from 347 sites in 46 countries and randomly allocated in a 3:3:3:1 ratio via Interactive Response Technology to 72 mg ligelizumab, 120 mg ligelizumab, 300 mg omalizumab, or placebo, dosed every 4 weeks, for 52 weeks. Patients allocated to placebo received 120 mg ligelizumab from week 24. The primary endpoint was change-from-baseline (CFB) in weekly Urticaria Activity Score (UAS7) at week 12, and was analysed in all eligible adult patients according to the treatment assigned at random allocation. Safety was assessed throughout the study in all patients who received at least one dose of the study drug. The studies were registered with , (PEARL-1) and (PEARL-2). Both trials are now complete. Between Oct 17, 2018, and Oct 26, 2021, 2057 adult patients were randomly allocated across both studies (72 mg ligelizumab n=614; 120 mg ligelizumab n=616; 300 mg omalizumab n=618, and placebo n=209). A total of 1480 (72%) of 2057 were female, and 577 (28%) of 2057 were male. Mean UAS7 at baseline across study groups ranged from 29·37 to 31·10. At week 12, estimated treatment differences in mean CFB-UAS7 were as follows: for 72 mg ligelizumab versus placebo, –8·0 (95% CI –10·6 to –5·4; PEARL-1), –10·0 (–12·6 to –7·4; PEARL-2); 72 mg ligelizumab versus omalizumab 0·7 (–1·2 to 2·5; PEARL-1), 0·4 (–1·4 to 2·2; PEARL-2); 120 mg ligelizumab versus placebo –8·0 (–10·5 to –5·4; PEARL-1), –11·1 (–13·7 to –8·5; PEARL-2); 120 mg ligelizumab versus omalizumab 0·7 (–1·1 to 2·5; PEARL-1), –0·7 (–2·5 to 1·1; PEARL-2). Both doses of ligelizumab were superior to placebo (p<0·0001), but not to omalizumab, in both studies. No new safety signals were identified for ligelizumab or omalizumab. In the phase 3 PEARL studies, ligelizumab demonstrated superior efficacy versus placebo but not versus omalizumab. The safety profile of ligelizumab was consistent with previous studies. Novartis Pharma.

更新日期：2023-11-23

点击分享查看原文

点击收藏

阅读更多本刊最新论文

全部期刊列表>>