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

Issued Date

2024-01-13

Resource Type

Article

eISSN

1474547X

DOI

10.1016/S0140-6736(23)01684-7

Scopus ID

2-s2.0-85178245469

Pubmed ID

38008109

Journal Title

Lancet (London, England)

Volume

403

Issue

10422

Start Page

147

End Page

159

Rights Holder(s)

SCOPUS

Bibliographic Citation

Lancet (London, England) Vol.403 No.10422 (2024) , 147-159

Suggested Citation

Maurer M., Ensina L.F., Gimenez-Arnau A.M., Sussman G., Hide M., Saini S., Grattan C., Fomina D., Rigopoulos D., Berard F., Canonica G.W., Rockmann H., Irani C., Szepietowski J.C., Leflein J., Bernstein J.A., Peter J.G., Kulthanan K., Godse K., Ardusso L., Ukhanova O., Staubach P., Sinclair R., Gogate S., Thomsen S.F., Tanus T., Ye Y.M., Burciu A., Barve A., Modi D., Scosyrev E., Hua E., Letzelter K., Varanasi V., Patekar M., Severin T., Rosana A., Ahmed A.W., Fabio A., Miguel Angel Tejedor A., Alfred A., Eng Kim A.G., Robert A., Ledit A., Petr A., Nandini A.S., Mohammad A., Natalia A., Anil B., Esther Serra B., Christine B., Annick B., Zsuzsanna B.C., Andrea B., Frederic B., Beata B.C., Gary D B., Jonathan B., Subhash Chandra B., Ramesh M B., Isabelle B.G., Ivan B., Knut B., Philipp B., Paula B., Regis C., Giorgio Walter C., Julia Maria Del C., Jaime Del C., Mamatha C., Yoon-Seok C., Amarjit C., Yi Hsing C., Yuko C., Soyun C., Jeong-Hee C., Chia-Yu C., Ronit C., Jonathan C., Roberta C., Claudia De La C., David M C., Pramila D., Inna D., Kenneth D., Michelle Joy D.V., James D., Stefano D.G., Diana D., John D., Richard D.M., Mohamed D., Heinrich D., Le Huu D., Sinan D., Marie Sylvie D., Anne Sophie D., Anton E., Kent E., Swarna E.B. Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials. Lancet (London, England) Vol.403 No.10422 (2024) , 147-159. 159. doi:10.1016/S0140-6736(23)01684-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/95745

Title

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

Author(s)

Maurer M.
 Ensina L.F.
 Gimenez-Arnau A.M.
 Sussman G.
 Hide M.
 Saini S.
 Grattan C.
 Fomina D.
 Rigopoulos D.
 Berard F.
 Canonica G.W.
 Rockmann H.
 Irani C.
 Szepietowski J.C.
 Leflein J.
 Bernstein J.A.
 Peter J.G.
 Kulthanan K.
 Godse K.
 Ardusso L.
 Ukhanova O.
 Staubach P.
 Sinclair R.
 Gogate S.
 Thomsen S.F.
 Tanus T.
 Ye Y.M.
 Burciu A.
 Barve A.
 Modi D.
 Scosyrev E.
 Hua E.
 Letzelter K.
 Varanasi V.
 Patekar M.
 Severin T.
 Rosana A.
 Ahmed A.W.
 Fabio A.
 Miguel Angel Tejedor A.
 Alfred A.
 Eng Kim A.G.
 Robert A.
 Ledit A.
 Petr A.
 Nandini A.S.
 Mohammad A.
 Natalia A.
 Anil B.
 Esther Serra B.
 Christine B.
 Annick B.
 Zsuzsanna B.C.
 Andrea B.
 Frederic B.
 Beata B.C.
 Gary D B.
 Jonathan B.
 Subhash Chandra B.
 Ramesh M B.
 Isabelle B.G.
 Ivan B.
 Knut B.
 Philipp B.
 Paula B.
 Regis C.
 Giorgio Walter C.
 Julia Maria Del C.
 Jaime Del C.
 Mamatha C.
 Yoon-Seok C.
 Amarjit C.
 Yi Hsing C.
 Yuko C.
 Soyun C.
 Jeong-Hee C.
 Chia-Yu C.
 Ronit C.
 Jonathan C.
 Roberta C.
 Claudia De La C.
 David M C.
 Pramila D.
 Inna D.
 Kenneth D.
 Michelle Joy D.V.
 James D.
 Stefano D.G.
 Diana D.
 John D.
 Richard D.M.
 Mohamed D.
 Heinrich D.
 Le Huu D.
 Sinan D.
 Marie Sylvie D.
 Anne Sophie D.
 Anton E.
 Kent E.
 Swarna E.B.

Author's Affiliation

Siriraj Hospital
 Université Saint-Joseph de Beyrouth
 Universitat Pompeu Fabra Barcelona
 University Medical Center Utrecht
 Johns Hopkins Asthma & Allergy Center
 Andreas Sygros Hospital
 Hiroshima University
 Allergy Medical Clinic
 Ajou University School of Medicine
 University of Melbourne
 Charité – Universitätsmedizin Berlin
 Bispebjerg Hospital
 Universidad Nacional de Rosario
 Humanitas Research Hospital
 Universitätsmedizin Mainz
 Colorado Allergy and Asthma Centers, P.C.
 University of Cincinnati College of Medicine
 University of Toronto
 Universidade Federal de São Paulo
 CHU de Lyon
 Sechenov First Moscow State Medical University
 Novartis International AG
 Wroclaw Medical University
 Guy's and St Thomas' NHS Foundation Trust
 University of Cape Town
 Scientific Medical Center of General Therapy and Pharmacology
 Y Patil University School of Medicine
 China Novartis Institutes for BioMedical Research
 Novartis Healthcare Private Limited
 Allergy and Immunology Associates of Ann Arbor

Corresponding Author(s)

Maurer M.

Other Contributor(s)

Mahidol University

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.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/95745

Collections

Scopus 2024