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Objective The objective of this study was to determine the efficacy of hydroxychloroquine (HCQ) in the primary thrombosis prevention of antiphospholipid antibody (aPL)-positive patients with no other systemic autoimmune diseases. Methods Under the auspices of Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking, a multicenter, international, randomized controlled trial (RCT) was initiated, in which persistently aPL-positive but thrombosis-free patients without systemic autoimmune diseases were randomized to receive HCQ or no treatment in addition to their standard regimen. The primary objective was the efficacy of HCQ in preventing the first thrombosis. The secondary objectives were the thrombosis incidence rate, and the effects of HCQ on aPL profile and mortality rate. Patients were risk-stratified based on antiplatelet agent use. The goal was to follow patients every 6 months for 5 years. Results We recruited 20 persistently aPL-positive patients (female: 19, mean age: 46.6 ± 9.9 years, and baseline antiplatelet medication: 14); 9/20 were randomized to HCQ. During the mean follow-up of 1.7 years, no patients developed thrombosis or a serious adverse event. The study was terminated early due to the low recruitment rate, exacerbated by the prolonged manufacturing shortage and significant price increase of HCQ in the United States. Conclusion Given that a small number of patients with a relatively short follow-up were enrolled in our RCT, and no patients developed thrombosis, we cannot accurately assess the effectiveness of HCQ for primary thrombosis prevention in persistently aPL-positive patients with no other systemic autoimmune diseases. Our experience suggests that conducting an international RCT, especially without pharmaceutical support, is an extremely challenging undertaking. [ABSTRACT FROM AUTHOR]

The antiphospholipid syndrome (APS) is defined by the presence of thrombosis and/or pregnancy morbidity in combination with the persistent presence of circulating antiphospholipid antibodies: lupus anticoagulant, anticardiolipin antibodies and/or anti-β2-glycoprotein I antibodies in medium to high titers. The management of thrombosis in patients with APS is a subject of controversy. This set of recommendations is the result of an effort to produce guidelines for therapy within a group of specialist physicians in Cardiology, Neurology, Hematology, Rheumatology and Internal Medicine, with a clinical and research focus on APS. [ABSTRACT FROM PUBLISHER]

The presence of antiphospholipid antibodies (aPL) has been closely related to the development of thrombosis and complications in pregnancy. However, not all patients with aPL will develop those clinical features. The exact pathogenic mechanisms leading to thrombosis and/or pregnancy morbidity are poorly understood. Currently, biomarkers which enable one to predict the prognosis of patients with positive aPL are not readily available. Current advances in genomics and proteomics provide the opportunity to discover novel biomarkers based on changes in concentration levels or post-translational modifications of proteins and peptides. These techniques are now being applied in various areas of medicine with very promising results. This review covers recent studies that have used this approach for a better understanding of the pathogenic mechanisms involved in the development of thrombosis in patients with antiphospholipid syndrome (APS). Although, there are very few qualified biomarkers that have arisen as a result of efforts in proteomics, it is expected that these techniques will deliver biomarkers that might ultimately identify different subgroups of APS patients with various prognoses that might have implications with respect to management and prognosis. [ABSTRACT FROM AUTHOR]

The complexity of the therapeutic approach in systemic lupus erythematosus (SLE) is increased by the large number of patients who do not respond to the first-line therapies and by relapses after initial clinical remission. In these patients, second-line drugs are often prescribed according to individual clinical decisions. The emergence of biological therapies has increased the therapeutic armamentarium available in these complex situations, but their use is limited by the lack of licensing. Available data on the use of rituximab in SLE rely on a large number of case reports and some observational studies. We analyzed current evidence on the therapeutic use of rituximab in adult SLE patients by a systematic review of reports included in the PubMed database between 2002 and 2007. A total of 188 SLE patients treated with rituximab were identified; 171 (91%) patients showed a significant improvement in one or more of the systemic SLE manifestations. There were 103 patients with lupus nephritis, with an overall rate of therapeutic response of renal involvement of 91%. Adverse events were reported in 44 (23%) patients; themost frequent were infections (19%). Although it is not yet possible to make definite recommendations, the global analysis of all cases reported to date support the off-label use of rituximab in severe, refractory SLE cases, whereas its use as a first-line therapy or in patients with a predominantly mild form of the disease is not advised. [ABSTRACT FROM AUTHOR]

Several systemic autoimmune conditions, including rheumatoid arthritis, systemic lupus erythematosus and antiphospholipid syndrome, are characterised by enhanced atherosclerosis and, consequently, higher cardiovascular morbidity and mortality rates. The association of these diseases with atherosclerosis suggests a common pathogenic mechanism. Genomic and proteomic studies per formed on atherosclerotic plaques have further confirmed the presence of a gene and protein profile similar to that observed in autoimmune diseases with cardiovascular risks. Human sera and body fluids have been analysed and have resulted in the identification of auto-antibodies that can be used as diagnostic markers in specific autoimmune diseases, and proteomic fingerprints of blood cells, tissues and body fluids have resulted in the identification of individual proteins or patterns of protein expression that are deregulated. The information provided by these proteomic studies is of diagnostic and therapeutic potential. In this review, we discuss new approaches available for assessing thrombotic risk in autoimmune diseases, focusing in the genomic and proteomic methods now available to deep into the origin of the mechanisms associated with vascular involvement in systemic autoimmune diseases. The increasing data available suggests that when treating patients with these autoimmune disorders, paying attention to the increased risk of cardiovascular disease is essential. [ABSTRACT FROM AUTHOR]