Background/Purpose: Sjögren’s disease (Sjo) is a systemic autoimmune disease. In 80% of the patients, Sjo is responsible for dryness, fatigue, and joint pain. In 10% of the patients, severe and potentially life-threatening systemic disease occur. B cell-targeted therapies have shown efficacy in some of these systemic manifestations, but some patients remain refractory to anti-CD20 therapy. Plasmablasts and plasma cells have been identified as key drivers of disease activity in Sjo, suggesting them as a potential therapeutic target. Daratumumab, a monoclonal antibody targeting CD38 and approved for multiple myeloma, depletes plasmablasts and plasma cells. Here, we present the two first cases of patients with severe Sjo complications refractory to rituximab (RTX) successfully treated with daratumumab.

Methods: Patient 1 is, an 18-year-old woman with a diagnosis of Sjo at age of 13 years old. She had positive anti-SSA and SSB antibodies, positive rheumatoid factor, hypergammaglobulinemia at 18 g/l and severe hypertriglyceridemia at 52 g/l due to an autoimmune hyperchylomicronemia with positive anti GPIHBP1 complicating Sjo. RTX treatment had no effect on triglyceride levels, leading to the decision to treat the patient with daratumumab at a dose of 16 mg per kilogram of body weight once a week for 4 weeks. Patient 2, a 68-year-old woman with Sjo, presented with positive anti-SSA and SSB antibodies, type II cryoglobulinemia-associated vaculitis, polyneuropathy, and glomerulonephritis. Despite multiple lines of treatment-included cyclophosphamide and the association rituximab/belimumab, vasculitis relapsed. Daratumumab treatment was initiated following the protocol used for Patient 1.

Results: The follow-up after daratumumab was 8 months for the 2 patients. After daratumumab treatment, Patient 1 showed normalized triglyceride levels (0.67 g/L), decreased gammaglobulin levels from 18 g/l to 9 g/l, and a dramatic decrease in anti-GPIHBP1 antibodies from 6121 U/ml to 234 U/ml(Figure 1). Patient 2 experienced no more purpura flare, negative proteinuria, normalization of complement level, negativation of cryoglobulinemia, and a very important decrease in rheumatoid factor titer from 339 to 48 UI/ml (Figure 2). For the 2 patients, no severe adverse events occurred during follow-up, and no hospitalization was required for the management of Sjo, infections or comorbidities.

Conclusion: Daratumumab may be an effective therapeutic strategy in severe and refractory Sjo patients, particularly when systemic manifestations are driven by pathogenic autoantibodies. Further studies are needed to assess the long-term efficacy and impact of daratumumab on autoreactive B cell repertoire and the room of daratumumab in the therapeutic arsenal of the disease.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-anti-cd38-treatment-with-daratumumab-in-two-cases-of-refractory-and-severe-sjogren-disease/