A Pilot Open-Label Phase II Trial of Rituximab for Non-Criteria Manifestations of Antiphospholipid Syndrome

Associate Professor of Medicine, Weill Medical College of Cornell University, New York, NY. .
Arthritis & Rheumatology (Impact Factor: 7.87). 02/2013; 65(2). DOI: 10.1002/art.37759
Source: PubMed

ABSTRACT BACKGROUND: Few studies address the treatment of non-criteria manifestations of antiphospholipid syndrome (APS). METHODS: The primary objective of this 12-month pilot, Phase II study was to evaluate the safety of rituximab in antiphospholipid antibody (aPL)-positive patients with non-criteria APS manifestations. The secondary objectives were to evaluate the effect of rituximab on aPL profile and non-criteria APS manifestations. Adult aPL-positive patients with thrombocytopenia, cardiac valve disease (CVD), skin ulcer, aPL-nephropathy (aPLN), and/or cognitive dysfunction (CD) received two doses of rituximab (1000mg) on days one and 15. Antiphospholipid antibody profiles and clinical outcome measures (COMs) were analyzed at preset time points, which were categorized as: "complete response (CR)", "partial response (PR)", "no response (NR)", and "recurrence (RC)". RESULTS: Two of 19 patients developed infusion reactions resulting in early termination. There were 12 serious and 49 non-serious adverse events. All patients with baseline positive lupus anticoagulant as well as anticardiolipin and anti-β(2) -glycoprotein-I antibody IgG tests remained positive at 24 and 52 weeks. The number of patients with CR/PR/NR/RC for COMs at 24 weeks was: 1/1/2/0 for thrombocytopenia; 0/0/3/- for CVD; 3/1/0/1 for skin ulcer; 0/1/0/0 for aPLN; and 3/1/1/- for CD. CONCLUSION: Our uncontrolled and non-randomized pilot study suggests that safety is consistent with rituximab's safety profile in aPL-positive patients; and despite no substantial change in aPL profiles, rituximab may be effective in controlling some but not all non-criteria aPL manifestations. © 2012 American College of Rheumatology.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The catastrophic antiphospholipid syndrome (CAPS) is characterized by thrombosis in more than three organs or systems developing over a short period of time. Despite conventional treatment with a combination of anticoagulation plus corticosteroids plus plasma exchange, and/or intravenous immunoglobulin, mortality remains high and some patients suffer from recurrent CAPS episodes. In selected patients, new therapies such as rituximab may be a treatment option. In this review, the rationale for using rituximab in CAPS is discussed.
    Therapeutic advances in musculoskeletal disease 02/2015; 7(1):26-30. DOI:10.1177/1759720X14554793
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Antiphospholipid syndrome (APS) or "Hughes Syndrome" is a prothrombotic disease characterized by thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). More than three decades have passed and experts are still uncovering new pieces of this disease complex pathogenesis and management. We searched literature using MEDLINE and PubMed databases focusing on the latest development on disease pathogenesis, risk assessment of thrombosis and treatment in APS. The phosphatidylinositol 3-kinase (PI3K)-AKT-mTORC pathway was most recently identified to have a crucial role in activating inflammation among endothelial vessel wall causing vascular lesions in APS. Additionally, new variables are being implemented to assess risk of thrombosis in APS patients. Global APS Score (GAPSS) utilizes cardiovascular risk factors and new autoimmune antibodies as part of the score assessment and is the most valid so far. It can be a promising tool in the future for prediction of thrombosis. Anticoagulation remains the corner stone in APS, however, many new potential therapeutic agents are developing and currently under investigation. The most recent advances in pathogenesis, risk stratification and treatment provide a platform for high yield studies with the ultimate goal of providing the optimal management to APS patients. This article is protected by copyrights. All rights reserved.
    European Journal of Clinical Investigation 04/2015; DOI:10.1111/eci.12449 · 2.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The association between antiphospholipid antibod-ies (aPL) and clinical problems goes beyond what is stated in the antiphospholipid syndrome (APS) classification criteria, namely thrombosis and pregnancy morbidity, and thrombocy-topenia is the most common non-criteria hematologic manifestation of aPL with a frequency ranging from 20 to 50 %. Thrombocytopenia is rarely severe, and hemorrhage is far less common than thrombosis. However, when anticoagulation is considered, it may constitute a clinical problem with increased bleeding risk. Furthermore, thrombocytopenia represents a risk factor for thrombosis in aPL-positive patients. Therefore, it is important to understand the pathogenesis and the clinical associations of thrombocytopenia to build the right medical approach in aPL-positive patients. In this paper, we review the literature on aPL/APS-associated thrombocytopenia and briefly discuss the other conditions that can result in thrombocyto-penia as they have commonalities with APS and their recognition is important to establish the most appropriate treatment strategy.
    Current Rheumatology Reports 03/2015; 17(3). DOI:10.1007/s11926-014-0494-8 · 2.45 Impact Factor