Brief report: induction of sustained remission in recurrent catastrophic antiphospholipid syndrome via inhibition of terminal complement with eculizumab.

Catastrophic antiphospholipid syndrome (CAPS) is characterized by histopathologic evidence of small vessel thrombosis, dysfunction of multiple organs occurring over a short period of time, and laboratory confirmation of the presence of antiphospholipid antibodies (aPL). Treatment of CAPS focuses on anticoagulation therapy and on removal of aPL that promote thrombosis by activating endothelial cells, monocytes, and platelets. Studies in animal models support the hypothesis that a more targeted intervention, such as complement inhibition, may be an effective means to prevent aPL-induced thrombosis. Herein we describe use of an inhibitor of complement activation to treat CAPS that was refractory to conventional therapy. Our patient was a young man who had recurrent CAPS characterized by multiple arterial thromboses in large and small vessels despite maximal anticoagulation, immunosuppression, and plasma exchange therapy. We treated him with eculizumab, an anti-C5 monoclonal antibody that blocks activation of terminal complement. Administration of eculizumab, at doses that blocked complement activity, aborted acute progressive thrombotic events, reversed thrombocytopenia, and was associated with no further clinical episodes of thrombosis during >3 years of therapy. This first report of the use and clinical efficacy of eculizumab, an inhibitor of complement activation, in the treatment of CAPS demonstrates both the importance of complement (specifically, terminal complement components) in the pathogenesis of CAPS and the therapeutic benefit of complement inactivation.

Shapira I ，Andrade D ，Allen SL ，Salmon JE ... -  《-》

Eculizumab in refractory catastrophic antiphospholipid syndrome: a case report and systematic review of the literature.

Tinti MG ，Carnevale V ，Inglese M ，Molinaro F ，Bernal M ，Migliore A ，De Cata A ... -  《-》

Case report: Timing of eculizumab treatment in catastrophic antiphospholipid syndrome.

Carrara C ，Mataj B ，Gastoldi S ，Ruggenenti P ，Sciascia S ，Roccatello D ... -  《Frontiers in Immunology》

Eculizumab Induces Sustained Remission in a Patient With Refractory Primary Catastrophic Antiphospholipid Syndrome.

Zikos TA ，Sokolove J ，Ahuja N ，Berube C ... -  《-》

Catastrophic antiphospholipid syndrome: The current management approach.

The current recommendation for catastrophic antiphospholipid syndrome (CAPS) management is the standard triple therapy with anticoagulation (AC), glucocorticoids (GCs), plasma exchange (PE), and/or intravenous immunoglobulins (IVIGs). Of note, only AC has a significant effect on the prognosis of these patients. However, from the experimental or basic point of view, there is only indirect evidence to advocate the use of these immunomodulatory therapies (GC, PE, and IVIG) in CAPS. Recently, there have been reports of severe or refractory CAPS patients treated with the monoclonal antibodies rituximab and eculizumab. The first blocks CD20, a surface protein expressed on the cytoplasmic membrane of B cells, and decreases the generation of pathogenic autoantibodies such as antiphospholipid (aPL) antibodies. The second binds with high affinity to C5 complement protein, inhibiting its cleavage and thus preventing the generation of C5b-C9 complex.

Rodriguez-Pintó I ，Espinosa G ，Cervera R 《-》