Emerging Targeted Therapies for Antiphospholipid Syndrome Go Far Beyond Blood Thinners
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A 2025 review in Arthritis and Rheumatology outlines a wave of clinical trials testing targeted, disease-modifying therapies for antiphospholipid syndrome, including daratumumab, CAR T cells, complement inhibitors, and certolizumab for obstetric APS. The authors argue that treatment must move beyond anticoagulation to address the underlying immune process.
Abstract
Antiphospholipid syndrome (APS) is an autoimmune thromboinflammatory disease defined by persistent antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin, anti-beta-2 glycoprotein I) and associated thrombosis and/or obstetric morbidity. Standard anticoagulation reduces thrombotic risk but does not address the underlying autoimmune process or non-thrombotic manifestations.
This review summarizes emerging therapeutic opportunities including B cell depletion and plasma cell-directed therapies (rituximab, belimumab, daratumumab, zanubrutinib, anti-CD19 CAR T cells), complement pathway inhibitors (eculizumab, C3/C5-targeted agents), BTK inhibitors, and anti-TNF agents for obstetric APS (certolizumab, IMPACT Study). Active trials include the DARE APS trial evaluating daratumumab and the IMPACT Study evaluating certolizumab in pregnant patients. The review argues for a disease-modifying paradigm targeting aPL production and downstream complement and coagulation activation, particularly for refractory or non-thrombotic manifestations.