Efficacy and safety of sequential therapy with subcutaneous belimumab and one cycle of rituximab in patients with systemic lupus erythematosus: the phase 3, randomised, placebo-controlled BLISS-BELIEVE study.

Autor:	Aranow C; Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA caranow@northwell.edu., Allaart CF; Leids Universitair Medisch Centrum, Leiden, The Netherlands., Amoura Z; Assistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Inserm UMRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Paris, France., Bruce IN; Kellgren Centre for Rheumatology, Manchester University Hospitals NHS Trust, Manchester, UK.; Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Cagnoli PC; University of Michigan Medical Center, Ann Arbor, Michigan, USA., Chatham WW; University of Alabama at Birmingham, Birmingham, Alabama, USA., Clark KL; Clinical Science, GSK, Stevenage, UK., Furie R; Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA., Groark J; Clinical Development, GSK, Collegeville, Pennsylvania, USA., Urowitz MB; Toronto Western Hospital, University of Toronto, Lupus Clinic, Toronto, Ontario, Canada., van Vollenhoven R; Amsterdam University Medical Center, Amsterdam Rheumatology Center, Amsterdam, The Netherlands., Daniels M; Global Medical Affairs, GSK, Brentford, UK., Fox NL; Clinical Development, GSK, Collegeville, Pennsylvania, USA., Gregan YI; Clinical Science Immunology, GSK, Collegeville, Pennsylvania, USA., Henderson RB; Clinical Biomarker Group, GSK, Stevenage, UK., van Maurik A; Clinical Biomarker Group, GSK, Stevenage, UK., Ocran-Appiah JC; Clinical Science, Respiratory and Immunology Clinical Research and Early Programs, GSK, Philadelphia, Pennsylvania, USA., Oldham M; Biostatistics, GSK, Stevenage, UK., Roth DA; Research and Development, GSK, Collegeville, Pennsylvania, USA., Shanahan D; Development Biostatistics, GSK, GSK House, Brentford, UK., Tak PP; Research and Development, GSK, Stevenage, UK., Teng YO; Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2024 Oct 21; Vol. 83 (11), pp. 1502-1512. Date of Electronic Publication: 2024 Oct 21.
DOI:	10.1136/ard-2024-225686
Abstrakt:	Objectives: Disease activity control in patients with systemic lupus erythematosus (SLE) with corticosteroid and immunosuppressant withdrawal is a treatment goal. We evaluated whether this could be attained with sequential subcutaneous belimumab (BEL) and one cycle of rituximab (RTX). Methods: In this phase 3, double-blind BLISS-BELIEVE trial (GSK Study 205646), patients with active SLE initiating subcutaneous BEL 200 mg/week for 52 weeks were randomised to intravenous placebo (BEL/PBO) or intravenous RTX 1000 mg (BEL/RTX) at weeks 4 and 6 while stopping concomitant immunosuppressants/tapering corticosteroids; standard therapy for 104 weeks (BEL/ST; reference arm) was included. Primary Endpoint: proportion of patients achieving disease control (SLE Disease Activity Index-2000 (SLEDAI-2K) ≤2; without immunosuppressants; prednisone equivalent ≤5 mg/day) at week 52 with BEL/RTX versus BEL/PBO. Major (alpha-controlled) secondary endpoints: proportion of patients with clinical remission (week 64; clinical SLEDAI-2K=0, without immunosuppressants/corticosteroids); proportion of patients with disease control (week 104). Other assessments: disease control duration, anti-dsDNA antibody, C3/C4 and B cells/B-cell subsets. Results: The modified intention-to-treat population included 263 patients. Overall, 16.7% (12/72) of BEL/PBO and 19.4% (28/144) of BEL/RTX patients achieved disease control (OR (95% CI) 1.27 (0.60 to 2.71); p=0.5342) at week 52. For major secondary endpoints, differences between BEL/RTX and BEL/PBO were not statistically significant. Anti-dsDNA antibodies and most assessed B cells/B-cell subsets were lower with BEL/RTX versus BEL/PBO. Mean disease control duration through 52 weeks was significantly greater with BEL/RTX versus BEL/PBO. Conclusions: BEL/RTX showed no superiority over BEL/PBO for most endpoints analysed; however, it led to significant improvements in disease activity markers compared with BEL/PBO. Further investigation of combination treatment is warranted. Trial Registration Number: NCT03312907. Competing Interests: Competing interests: CA has received research support from GSK; consulting fees from GSK, AstraZeneca, BMS, Kezar Life Sciences Inc., Merck Sharp & Dohme and Alumis Inc. CFA has received research support from Janssen, AbbVie, and Eli Lilly. ZA has received research support from GSK, Roche, AstraZeneca, and Amgen; and consulting fees from GSK, AstraZeneca, Amgen, Kezar Life Sciences Inc, and Novartis. INB has received research support from Genzyme, Sanofi, and GSK; consulting fees from AstraZeneca, Eli Lilly, Aurinia Pharmaceuticals, GSK, and ILTOO; and has served as an advisory board member for AstraZeneca and Merck Serono. INB is a National Institute for Health Research (NIHR) Senior Investigator Emeritus and is funded by the NIHR Manchester Biomedical Research Centre (NIHR203308). PCC has received consulting and speaker fees from GSK, Aurinia Pharmaceuticals, and Eli Lilly. WWC has received research support from GSK, UCB, Amgen, Pfizer, and BMS; consulting fees from GSK and Aurinia Pharmaceuticals; honoraria from GSK and Aurinia Pharmaceuticals for disease awareness presentations and curricula on achieving disease control and remission in SLE. RF has received research support and consulting fees from GSK. MBU has received research support from GSK; consulting fees from GSK and UCB; and speaker fees from GSK, Eli Lilly, and AstraZeneca. RvV has received research support for educational programmes and institutional grants from AstraZeneca, Pfizer, and UCB; consulting fees from AbbVie, AstraZeneca, Biogen, Biotest, BMS, Galapagos, Gilead, Janssen, Pfizer, Sanofi, Servier, UCB, and Vielabio; speaker fees from AbbVie, Galapagos, GSK, Janssen, Pfizer, and UCB; and research support from BMS, GSK Eli Lilly, and UCB. RBH, AvM, JCO-A, MO and DAR are employees of GSK and hold stocks and shares in the company. RBH is also an inventor for the following patents: US-20220195062-A1, US-11180569-B2, and US-20180265588-A1. KLC, JG, MD, YIG, DS and PPT were employees of GSK at the time of the study and hold stocks and shares in the company. NLF is a former employee and consultant for GSK and holds stocks in the company. YOT has received unrestricted research grants from GSK, Aurinia Pharmaceuticals, and Vifor Pharma; and consulting fees from Aurinia Pharmaceuticals, Novartis, GSK, Kezar Life Sciences Inc, Vifor Pharma, and Otsuka Pharmaceuticals (paid to Leiden University Medical Center). (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)
Databáze:	MEDLINE
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