Obexelimab in Systemic Lupus Erythematosus With Exploration of Response Based on Gene Pathway Co‐Expression Patterns: A Double‐Blind , Randomized, Placebo‐Controlled , Phase 2 Trial

作者：Joan T. Merrill, Joel M. Guthridge, Miles Smith, Joshua June, Fotios Koumpouras, Wambui Machua, Anca Askanase, Arezou Khosroshahi, Saira Z. Sheikh, Gaurav Rathi, Bart Burington, Paul Foster, Mark Matijevic, Sujata Arora, Xiaodong Wang, Minggeng Gao, Stephen Wax, Judith A. James, Debra Zack · 发表于：Arthritis & Rheumatology · 年份：2023 · DOI：10.1002/art.42652 · 被引用次数：66 · 研究领域：Systemic Lupus Erythematosus Research、Monoclonal and Polyclonal Antibodies Research、T-cell and B-cell Immunology

OBJECTIVE: Obexelimab is an investigational, bifunctional, noncytolytic monoclonal antibody that binds CD19 and FcyRIIb to inhibit B cells, plasmablasts, and plasma cells. This trial evaluated the efficacy and safety of obexelimab in the treatment of patients with systemic lupus erythematosus (SLE). METHODS: During screening, patients with active, non-organ-threatening SLE received corticosteroid injections to ameliorate symptoms while immunosuppressants were withdrawn (≤10 mg/day prednisone equivalent and ≤400 mg/day hydroxychloroquine allowed). Patients with improved disease activity were randomized 1:1 to obexelimab 5 mg/kg intravenously or placebo once every 2 weeks until week 32 or loss of improvement (LOI). RESULTS: In this study, 104 patients were randomized. Analysis of the primary endpoint, proportion of patients reaching week 32 without LOI, used an efficacy-evaluable (EE) population defined as patients who completed the study or withdrew for flare or treatment-related toxicity. This endpoint did not reach statistical significance: 21 of 50 obexelimab-treated patients (42.0%) versus 12 of 42 patients (28.6%) treated with a placebo (P = 0.183). Time to LOI was increased in obexelimab-treated patients versus patients treated with a placebo in the EE (hazard ratio [HR] 0.53, P = 0.025) and intention-to-treat (HR 0.59, P = 0.062) populations. In obexelimab-treated patients, B cells decreased approximately 50%, and trough concentration and inclusion in baseline gene expr...