Fecha de publicación: -- Fuente: PubMed "nature biotechnology" Lancet Rheumatol. 2026 Nov 8:S2665-9913(26)00315-2. doi: 10.1016/S2665-9913(26)00315-2. Online ahead of print.ABSTRACTBACKGROUND: B cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE) and are a therapeutic target. We therefore assessed the efficacy and safety of obinutuzumab β, a glycoengineered type II anti-CD20 monoclonal antibody, in patients with active SLE.METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, we enrolled patients who were aged 18-80 years, fulfilled the 2019 European Alliance of Associations for Rheumatology-American College of Rheumatology classification criteria for SLE, and had active disease (defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] score of 8 or more and positivity for antinuclear antibodies or anti-double stranded DNA antibodies) at 30 tertiary hospitals in China. Participants were randomly allocated 1:1 to receive obinutuzumab β or placebo, stratified by SLEDAI-2K score and 24-h urine protein level. Patients, investigators, and the sponsor were masked to treatment allocation. Patients received intravenous infusions of obinutuzumab β (1000 mg) or placebo on days 1, 15, 169, 183, 365, and 379. All patients maintained their background standard therapy. The primary efficacy endpoint was the proportion of patients with an SLE Responder Index (SRI)-4 response at week 12 assessed in all patients who were randomly assigned and received at least one dose of study treatment (ie, the full analysis set). Safety was assessed in all patients who received any study treatment and had at least one post-dose safety assessment (ie, the safety analysis set) over 52 weeks. The study was registered at ClinicalTrials.gov (NCT05796206) and is complete. People with lived experience were not involved as research partners in this study.FINDINGS: Between May 26, 2023, and July 29, 2024, 171 patients were screened for eligibility. Of these, 123 patients were randomly assigned to receive obinutuzumab β (n=61) or placebo (n=62) and were included in both the full analysis set and safety analysis sets. The mean age was 36·1 years (SD 10·3). 115 (93%) of 123 patients were female, eight (7%) were male, and 117 (95%) were Han Chinese ethnicity. At week 12, 32 (52%) of 61 patients in the obinutuzumab β group and 21 (34%) of 62 in the placebo group had an SRI-4 response (adjusted risk difference 19 percentage points, 95% CI 3-36; p=0·022). Serious adverse events occurred in 12 (20%) patients in the obinutuzumab β group and 14 (23%) in the placebo group. One fatal treatment-emergent adverse event (sepsis) occurred in the placebo group.INTERPRETATION: Obinutuzumab β plus standard therapy improved SRI-4 response at week 12 in Chinese patients with active SLE, with a generally manageable safety profile over 52 weeks. These phase 2 findings support further evaluation and longer-term safety follow-up.FUNDING: Beijing Mabworks Biotech.PMID:43000040 | DOI:10.1016/S2665-9913(26)00315-2