B cell depletion and BAFF receptor blockade with ianalumab (VAY736) for the treatment of moderate-to-severe systemic lupus erythematosus: a phase 2 randomised, double-blind, placebo-controlled trial with subsequent open-label treatment
Issued Date
2025-01-01
Resource Type
ISSN
00034967
eISSN
14682060
Scopus ID
2-s2.0-105025241510
Pubmed ID
41353079
Journal Title
Annals of the Rheumatic Diseases
Rights Holder(s)
SCOPUS
Bibliographic Citation
Annals of the Rheumatic Diseases (2025)
Suggested Citation
Agmon-Levin N., Ignatenko S., Gordienko A., Cortés-Hernández J., Narongroeknawin P., Romanowska-Próchnicka K., Shen N., Ciferská H., Kodera M., Cheng-Chung W.J., Leszczynski P., Lan J.L., Mysler E., Wojciechowski R., Tarr T., Vishneva E., Chen Y.H., Kaneko Y., Finzel S., Hoi A., Okada M., Koolvisoot A., Lee S.S., Lie D., Kaneko H., Rojkovich B., Sun L., Zotkin E., Viallard J.F., López B.P.M., Ghanshani S.A., Lau C., Avrameas A., Sips C., Oliver S.J. B cell depletion and BAFF receptor blockade with ianalumab (VAY736) for the treatment of moderate-to-severe systemic lupus erythematosus: a phase 2 randomised, double-blind, placebo-controlled trial with subsequent open-label treatment. Annals of the Rheumatic Diseases (2025). doi:10.1016/j.ard.2025.11.015 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/113678
Title
B cell depletion and BAFF receptor blockade with ianalumab (VAY736) for the treatment of moderate-to-severe systemic lupus erythematosus: a phase 2 randomised, double-blind, placebo-controlled trial with subsequent open-label treatment
Author(s)
Agmon-Levin N.
Ignatenko S.
Gordienko A.
Cortés-Hernández J.
Narongroeknawin P.
Romanowska-Próchnicka K.
Shen N.
Ciferská H.
Kodera M.
Cheng-Chung W.J.
Leszczynski P.
Lan J.L.
Mysler E.
Wojciechowski R.
Tarr T.
Vishneva E.
Chen Y.H.
Kaneko Y.
Finzel S.
Hoi A.
Okada M.
Koolvisoot A.
Lee S.S.
Lie D.
Kaneko H.
Rojkovich B.
Sun L.
Zotkin E.
Viallard J.F.
López B.P.M.
Ghanshani S.A.
Lau C.
Avrameas A.
Sips C.
Oliver S.J.
Ignatenko S.
Gordienko A.
Cortés-Hernández J.
Narongroeknawin P.
Romanowska-Próchnicka K.
Shen N.
Ciferská H.
Kodera M.
Cheng-Chung W.J.
Leszczynski P.
Lan J.L.
Mysler E.
Wojciechowski R.
Tarr T.
Vishneva E.
Chen Y.H.
Kaneko Y.
Finzel S.
Hoi A.
Okada M.
Koolvisoot A.
Lee S.S.
Lie D.
Kaneko H.
Rojkovich B.
Sun L.
Zotkin E.
Viallard J.F.
López B.P.M.
Ghanshani S.A.
Lau C.
Avrameas A.
Sips C.
Oliver S.J.
Author's Affiliation
Monash University
Sun Yat-Sen University
Tel Aviv University
Charles University
Charité – Universitätsmedizin Berlin
Universitätsklinikum Freiburg
China Medical University
Medical University of Warsaw
Semmelweis Egyetem
Hospital Universitari Vall d'Hebron
Novartis International AG
China Medical University Hospital
Poznan University of Medical Sciences
Keio University School of Medicine
Medical School of Nanjing University
Hospital de La Santa Creu I Sant Pau
Renji Hospital
Siriraj Hospital
Chung Shan Medical University Hospital
Általános Orvostudományi Kar
Veterans General Hospital-Taichung Taiwan
Chonnam National University Medical School
Hopital Haut-Lévêque C.H.U de Bordeaux
Military Medical Academy, Saint Petersburg
St. Luke's International Hospital Tokyo
V.A. Nasonova Research Institute of Rheumatology
Phramongkutklao College of Medicine
Japan Community Healthcare Organization Chukyo Hospital
Novartis India Limited
Organizacion Medica de Investigacion
University Hospital No. 2
National Centre for Global Health and Medicine
LLC Family Clinic
Sun Yat-Sen University
Tel Aviv University
Charles University
Charité – Universitätsmedizin Berlin
Universitätsklinikum Freiburg
China Medical University
Medical University of Warsaw
Semmelweis Egyetem
Hospital Universitari Vall d'Hebron
Novartis International AG
China Medical University Hospital
Poznan University of Medical Sciences
Keio University School of Medicine
Medical School of Nanjing University
Hospital de La Santa Creu I Sant Pau
Renji Hospital
Siriraj Hospital
Chung Shan Medical University Hospital
Általános Orvostudományi Kar
Veterans General Hospital-Taichung Taiwan
Chonnam National University Medical School
Hopital Haut-Lévêque C.H.U de Bordeaux
Military Medical Academy, Saint Petersburg
St. Luke's International Hospital Tokyo
V.A. Nasonova Research Institute of Rheumatology
Phramongkutklao College of Medicine
Japan Community Healthcare Organization Chukyo Hospital
Novartis India Limited
Organizacion Medica de Investigacion
University Hospital No. 2
National Centre for Global Health and Medicine
LLC Family Clinic
Corresponding Author(s)
Other Contributor(s)
Abstract
Objectives: B cell depletion or B cell activating factor (BAFF) blockade has shown benefits in systemic lupus erythematosus (SLE). We compared ianalumab, a monoclonal antibody targeting BAFF receptor (BAFF-R)-expressing B cells to lyse B cells and block BAFF-R, with placebo for SLE treatment combined with standard therapies. Methods: Patients with active SLE were randomised (1:1) to monthly subcutaneous ianalumab 300 mg or placebo. The primary outcome was a composite of SLE Responder Index (SRI)-4 at week 28 in patients successfully achieving corticosteroid (CS) tapering criteria. Patients subsequently received open-label (OL) ianalumab until week 48, followed by exploratory assessments at week 52 and off-treatment to week 68. Safety monitoring continued until B cell recovery. This report describes interim analyses conducted on the week 68 dataset. Results: Sixty-seven patients were randomised and received blinded treatments until week 28. The primary composite endpoint was more frequently achieved with ianalumab vs placebo: 15/34 (44.1%) vs 3/33 (9.1%), with responses sustained to week 52 and replicated by placebo transitioned to OL ianalumab: 15/33 (45.5%) and 13/32 (40.6%). Positive treatment effects were consistently observed across other lupus disease activity outcomes (SRI-6, Definition of Remission in SLE, Lupus Low Disease Activity State, flare reduction, and CS use) at week 28, with clinical benefits until weeks 52 and 68. Ianalumab was not associated with increased serious adverse events or serious infections. Nonserious local injection site reactions occurred more frequently with ianalumab. Conclusions: At week 28, reduced disease activity was observed in patients with SLE receiving ianalumab plus standard therapies compared with those receiving standard therapies alone, with sustained benefits with further treatment until 1 year, which was well tolerated.