Publication Type : Journal Article
Publisher : Elsevier BV
Source : The Lancet
Url : https://doi.org/10.1016/s0140-6736(23)01684-7
Campus : Faridabad
School : School of Medicine
Department : Dermatology
Year : 2024
Abstract : Background 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. Methods 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 ClinicalTrials.gov, NCT03580369 (PEARL-1) and NCT03580356 (PEARL-2). Both trials are now complete. Findings 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. Interpretation 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. Funding Novartis Pharma.
Cite this Research Publication : Marcus Maurer, Luis Felipe Ensina, Ana Maria Gimenez-Arnau, Gordon Sussman, Michihiro Hide, Sarbjit Saini, Clive Grattan, Daria Fomina, Dimitrios Rigopoulos, Frederic Berard, Giorgio Walter Canonica, Heike Rockmann, Carla Irani, Jacek C Szepietowski, Jeffrey Leflein, Jonathan A Bernstein, Jonny G Peter, Kanokvalai Kulthanan, Kiran Godse, Ledit Ardusso, Olga Ukhanova, Petra Staubach, Rodney Sinclair, Shaila Gogate, Simon Francis Thomsen, Tonny Tanus, Young Min Ye, Alis Burciu, Avantika Barve, Darshna Modi, Emil Scosyrev, Eva Hua, Kerstin Letzelter, Vineeth Varanasi, Manmath Patekar, Thomas Severin, Agondi Rosana, Al Waily Ahmed, Almerigogna Fabio, Alonso Miguel Angel Tejedor, Ammoury Alfred, Anne Goh Eng Kim, Anolik Robert, Ardusso Ledit, Arenberger Petr, AS Nandini, Asefi Mohammad, Astafieva Natalia, Badhwar Anil, Baldrich Esther Serra, Bangert Christine, Barbaud Annick, Bata-Csorgo Zsuzsanna, Bauer Andrea, Berard Frederic, Bergler-Czop Beata, Berman Gary D, Bernstein Jonathan, Bharija Subhash Chandra, Bhat Ramesh M, Boccon-Gibod Isabelle, Botev Ivan, Brockow Knut, Buck Philipp, Busse Paula, Campos Regis, Canonica Giorgio Walter, Carla Irani, Carmen Julia Maria Del, Carpio Jaime Del, Chadalavada Mamatha, Chang Yoon-Seok, Cheema Amarjit, Chen Yi Hsing, Chinuki Yuko, Cho Soyun, Choi Jeong-Hee, Chu Chia-Yu, Confino Ronit, Corren Jonathan, Criado Roberta, Cruz Claudia De La, Cypcar David M, Daftary Pramila, Danilycheva Inna, Dawes Kenneth, De Vera Michelle Joy, Deangelo James, Del Giacco Stefano, Deleanu Diana, Delgado John, DeMera Richard, Denguezli Mohamed, Dickel Heinrich, Doanh Le Huu, Dogan Sinan, Doutre Marie Sylvie, Dupond Anne Sophie, Edin Anton, EDWARD Kent, Ekanayake-Bohling Swarna, Elbirt Daniel, Elkayam David, Ellis Anne, Emanuel Shaunagh, Emeliyanov Alexander, Engin Burhan, Ensina Luis Felipe, Ercoreca Ignacio Antepara, Ergun Safiye, Estebaranz Jose Luis Lopez, Fassakhov Rustem, Fomina Daria, Ford Linda, Francomano Mariangela, Funkhouser Todd, Gagnon Remi, Galimberti Ricardo, Galvan Calle Cesar Alberto, Galvao Clovis, Gattolin Gabriel, Ghislain Pierre-Dominique, Gimenez Arnau Ana Maria, Ginchansky Elliot, Giordano-Labadie Francoise, Givirovsky Stanislav, Godse Kiran, Gogate Shaila, Goldsobel Alan, Gomez Francisca, Gomez Rene Maximiliano, Gonzalez Erika, Gonzalez Paula Ribo, Gospodinov Dimitar, Grattan Clive, Grosber Martine, Gross Gary, Guimera Martin-Neda Francisco Jose Gomez, Gyulai Rolland, Hadvabova Svetlana, Hadzavdic Suzana Ljubojevic, Hamam Hadi, Hasicova Daniela, Hayama Koremasa, Hissaria Pravin, Hjerppe Anna, Hlinka Ivan, Horrillo Moises Labrador, Hsu Connie, Huang Yu-Huei, Hussain Iftikhar, Igarashi Atsuyuki, IMKO-WALCZUK Beata, Inaloz Huseyin Serhat, Intravaia Rossella, Jain Neal, Jain Sanjeev, Jain Sanjeev, Jakob Thilo, Javier Ruth Cerino, João Antonio, Jozefowicz Luiza Marek, Jung Chang-Gyu, Kaatz Martin, Kacar Nida, Kanarek Henry, Karlova Iva, Kastanayan Alexander, Kazandjieva Jana, Kern Johannes, Kessel Aharon, Khanna Neena, Kim HeeJoo, Kim Nancy, Kim Sang-Ha, Kim Tae-bum, Kingo Kulli, Kleinheinz Andreas, Komova Janka, Kompoti Evangelia, Kopal Tomas, Kozub Peter, Krasowska Dorota, Krecisz Beata, Kreft Burkhard, Kubota Satsuki, Kudo Hitoshi, Kulkarni Teja, Kulthanan Kanokvalai, Kume Akihiro, Kupczyk Maciej, Lain Edward, Lanier Bobby, Lapeere Hilde, Lasanta Griselle Ortiz, Lazareva Svetlana, Lazzeri Laura, Ledford Dennis, Lee Donghun, Lee Haur Yueh, Leflein Jeffrey, Leitz Nicolas, Levin Nancy, Lima Hermenio, Lippert Undine, Lipson Brian, Luna Paula, Magarinos Gabriel, Mahajan Satyaprakash, Makris Michail, Malbran Alejandro, Manjra Ahmed Manjra, Manning Michael, Manrique Maria, Marcipar Adriana, Marini Mariano, Marmol Veronique Del, Maspero Jorge, Matsuda Tomoko, Matz Jonathan, Maurer Marcus, McFalda Wendy, Mclaughlin Anne, Medina Iris, Mehta Rajesh Dutt, Meller Stephan, MELTZER Steven, Meshkova Raisa, Mihalache Dorin, Miquel Francisco Javier, Mokni Mourad, Molhoek J, Montano Efrain, Mueller Sabine, Munoz Javier Pedraz, Nagakura Toshikazu, Narbutt Joanna, Nart Ignasi Figueras, Nebrida-Idea Ma. Lourdes M, Nguyen Trong Hao, Niesmann Johannes, Ninet Violeta Zaragoza, Noguchi Hiromitsu, Nomura Yuko Chinuki, Nowicki Roman, Omi Tokuya, Onder Robert, Orojan Ivan, Ortiz de Frutos Francisco Javier, Papp Kim, Parisi Claudio, Park Chun Wook, Park Heungwoo, Park Jungwon, Park Young Min, Parra Viviana, Passeron Thierry, Pasteur Justine, Patil Shivakumar, Patrascu Vergil, Pauser Sylvia, Pelc Anna Wojas, Peter Jonathan Grant, Pfuetzner Wolfgang, Pimpinelli Nicola, Pinter Andreas, Pizarro Cristian, Pizinger Karel, Plutinska Jarmila, Popov Todor, Popova Veronika, Puga Marta Ferrer, Pulido Lara Ferrandiz, Purcaru Anca, Raap Ulrike, Rajchel Anna, Ramey John, Ramiscal Ma Deanna Santos, Ramon German Dario, Rehman Syed, Reich Adam, Reider Norbert, Ress Krista, Rigopoulos Dimitrios, Rivas Enrique, Rockmann Heike, Roquet-Gravy Pierre-Paul, Rottem Menachem, Rowell Vermen Verallo, Rueff Franziska, Ruiz Juan Alberto Ruano, Russo Juan, Saff Ronald, Saini Sarbjit, Salazar Maria, Salvador Juan Francisco Silvestre, Sanchez Jorge, Sandru Florica, Scarupa Mark, Schaekel Knut, Schliemann Sibylle, Schrijvers Rik, Schwarz Beate, Schwinn Andreas, Sekhsaria Sudhir, Senturk Nilgun, Seo Seong Jun, Serna Mercedes Rodriguez, Serpa Faradiba, Shapero Paul A, Shinkawa Eriko, Simon Jan-Christoph, Sinclair Rodney, Singer Ralfi, Siri Dareen D, Sitz Karl, Smialowski Adam, Smith Andrew, Soerensen Morten, Sondermann Wiebke, Song Haejun, Sonin Dmitrii, Soong Weily, Soteres Daniel, Staevska-Kotasheva Maria, Staubach-Renz Petra, Subash Nisha Su Yien, Sussman Gordon, Svensson Ake Svensson, Syrigou Ekaterini, Szegedi Andrea, Szepietowski Jacek, Takahagi Shunsuke, Tal Yuval, Talreja Neetu, Tan Wooi Chiang, Tan Ricardo, Tang Jyh Jong, Tanus Tonny, Tarpay Martha, Tee Shang Ian, Teller Craig, Tetart Florence, Thanh Aurelie Du, Thevarajah Suganthi, Thomsen Simon Francis, Thornblade Carl, Tjioe Milan, Tolcachier Alberto, Tolentino Celeste, Tsianakas Athanasios, Tsingov Ilia, Turki Hamida, Ukhanova Olga, Ulrich Jens, Uslu Meltem, Valenzuela Fernando, Valle Solange, van Doorn Martijn, Vankova Jirina, Vartak Suneel, Vidouria Christine, Volc Sebastian, Volcheck Gerald, Wagner Nicola, Walecka-Herniczek Irena, Wattanakrai Penpun, Wedi Bettina, Weinstein Steven, Wessagowit Vesarat, Windom Hugh, Yagami Akiko, Yamamoto Aisaku, Yasumoto Shinichiro, Ye Young Min, Yepez Jose Cevallos, Youn Sang Woong, Zelenkova Hana, Ziganshin Oleg, Zook Matthew, Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials, The Lancet, Elsevier BV, 2024, https://doi.org/10.1016/s0140-6736(23)01684-7