Assessment of the use of biologic drugs in the treatment of primary antiphospholipid syndrome.

Abstract

The objective of this review was to assess the clinical efficacy, safety, and immunological effects of biologic therapies in patients with primary APS (pAPS) and catastrophic APS (CAPS). A systematic literature review was performed using PubMed and Embase (January 2005-January 2025), including studies involving adult patients diagnosed with pAPS or CAPS treated with rituximab, eculizumab, belimumab, or daratumumab. Data on clinical features, therapeutic indications, treatment responses, serological changes, and adverse events were extracted and synthesized. Fifty publications, encompassing over 100 patients, were included. Rituximab was the most frequently used biologic therapy and showed substantial efficacy in haematologic and cutaneous manifestations, notably thrombocytopenia and livedoid vasculopathy, though with limited impact on aPL levels. Eculizumab was effective in complement-mediated presentations such as thrombotic microangiopathy (TMA), thrombocytopenia, and renal involvement, with minimal serological changes. Belimumab led to both clinical and serologic improvement in select high-risk individuals. Daratumumab, reported in a single refractory case, temporarily reduced aPL titres, suggesting potential benefit from plasma cell-targeted approaches. Biologic therapies may represent valuable adjunctive options for specific APS phenotypes, especially refractory or complement-driven cases. However, the data remain limited by the heterogeneity in patient populations, the absence of standardized disease activity metrics, and unclear definitions of treatment response. Future studies should prioritize multicentre prospective designs, standardized outcome measures, and biomarker-driven stratification to guide personalized use of biologics in APS.