Promising therapeutic approach for systemic lupus erythematosus
Phase II study shows clinical improvement with daratumumab
A team led by PD Dr. Tobias Alexander, head of the Translational Rheumatology program area at the DRFZ and of the rheumatology outpatient clinic at Charité – Universitätsmedizin Berlin, has shown in a phase-II study that treatment of SLE patients with daratumumab, a drug directed against the CD38 molecule, can significantly reduce disease activity. Among other effects, daratumumab eliminates plasma cells, which are considered key drivers of the disease through production of autoantibodies. The study results were published in the renowned journal Nature Communications.
A new phase II study led by PD Dr. Tobias Alexander, head of the Translational Rheumatology program area at the DRFZ and of the rheumatology outpatient clinic at Charité, provides promising evidence for a new treatment approach for patients with systemic lupus erythematosus (SLE) who have responded inadequately to previous therapies. In the study, published in Nature Communications, treatment with the anti-CD38 antibody daratumumab led to rapid and sustained clinical improvement as well as a marked reduction in disease-relevant autoantibodies.
In the phase II trial, ten women with active SLE were treated, all of whom had shown an inadequate response to at least two previous immunosuppressive therapies. In addition to their background medication, the patients received eight weekly subcutaneous injections of daratumumab. Alongside a significant reduction in disease-relevant autoantibodies, the researchers observed rapid and sustained clinical improvement across all organ systems examined. The study also revealed clear immunological changes: treatment with daratumumab led to a depletion of circulating antibody-secreting cells, a reduction in inflammatory type I interferon activity, and profound modulation of T-cell responses. These findings underscore the central role of antibody-producing cells in the development and persistence of SLE.
Daratumumab is an antibody drug against CD38, a molecule that is highly expressed particularly on antibody-secreting cells. The newly published study data build upon the group´s earlier findings from a small case series, suggesting that targeted CD38 therapy could also have therapeutic potential in autoimmune diseases such as SLE.
