Background:Autoantibody production by long-lived plasma cells (PCs) have been implicated in the pathogenesis of systemic lupus erythematosus (SLE) but targeting them remains a therapeutic challenge.Objectives:We aimed to investigate the safety and efficacy of the anti-CD38 monoclonal antibody daratumumab in moderate to severe SLE. This reagent depletes PCs and is approved for the treatment of multiple myeloma.Methods:A single-center, phase 2, open-label investigator-initiated study was conducted in 10 patients with SLE receiving background standard therapy. Eligible patients were adults meeting the 2019 EULAR/ACR classification criteria, had a baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6, were positive for anti-double-stranded (ds)DNA antibodies and had failed or did not tolerate at least 2 previous state-of-the-art immunosuppressive drugs. Patients received 8 subcutaneous injections once weekly of 1800mg daratumumab and were followed-up for 36 weeks. Primary endpoint was the reduction of anti-dsDNA antibody levels at week 12. Secondary endpoints included safety and tolerability, reductions in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and Clinical Disease Activity Index (CDAI), SRI-4 responses, pharmacokinetics and immunological changes. This trial was supported by Janssen-Cilag and registered at www.clinicaltrials.gov (NCT04810754).Results:Between August 2021 and January 2023, 10 patients were enrolled and received at least six doses of daratumumab. Anti-dsDNA antibodies decreased from a median 166.3 at baseline to 61.1 U/ml at week 12 (p=0.002), accompanied by significant clinical improvements, reflected in median reductions of SLEDAI-2K from 12 to 4 (p=0....

LBA0007 SAFETY AND EFFICACY OF DARATUMUMAB IN SYSTEMIC LUPUS ERYTHEMATOSUS – A SINGLE-CENTER PHASE 2 OPEN-LABEL TRIAL

10.1136/annrheumdis-2024-eular.LBA26