Abetimus sodium

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease that significantly affects health-related quality of life (HRQOL): physical, psychologic, mental, and social aspects of well-being that are influenced by disease, in the context of life experiences and expectations specific to each patient1. A relapsing, remitting chronic disease, SLE results in disability in 20%–40% of afflicted young and middle-aged women and men2. In patients with SLE, HRQOL is influenced by disease activity and symptoms of fatigue, depression, pain, sleep disturbances, and cognitive dysfunction3. Across 5 randomized controlled trials (RCT) in SLE, baseline HRQOL scores were low and were similar to those of subjects following myocardial infarction or with chronic congestive heart failure4. Lower scores were highly correlated with history of renal disease, presence of anti-dsDNA antibodies, higher disease activity scores by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and/or Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA-SLEDAI), hypocomplementemia, African American descent, and age. A variety of therapeutic interventions, including pharmacologic and biologic therapies, have been shown in RCT to improve HRQOL, including prasterone, mycophenolate mofetil, abetimus sodium, oral contraceptive, and hormone replacement therapy in the SELENA trials, as well as monoclonal antibodies epratuzumab and belimumab5,6,7,8. In 1998, an international consensus conference on outcome measures in rheumatology (OMERACT 4) recommended that 4 core domains be assessed in RCT and longitudinal observational studies (LOS) in SLE: disease activity, HRQOL, adverse events, and damage9. OMERACT has also recommended that both generic and disease-specific instruments be utilized to measure HRQOL. Ongoing efforts to develop promising therapies for SLE have demonstrated the importance of including patient-reported outcomes (PRO) to assess HRQOL in RCT. Measurement of HRQOL adds a unique dimension to … Address correspondence to Dr. Strand; E-mail: vstrand{at}stanford.edu

Loss of B‐cell tolerance is a hallmark feature of the pathogenesis in systemic lupus erythematosus (SLE), an autoimmune disease that is characterized by hypergammaglobulinemia and autoantibody production. These autoantibodies lead to formation of immune‐complex deposition in internal organs causing inflammation and damage. Autoreactive B‐cells are believed to be central in the pathophysiology of SLE. Other than its role in the production of antibodies that mediate humoral immune response, B‐cells also function as antigen‐presenting cells and are capable of activating T‐cells. Activated B‐cells may also produce pro‐inflammatory cytokines that aggravate local inflammation. Abnormal B‐cell homeostasis has been described in SLE patients. This may occur as a result of intrinsic B‐cell defect or from aberrant regulation by maturation and survival signals. B‐cell‐based therapy is the current mainstream of research and development of novel therapies in SLE patients with severe and refractory disease. Potential cellular and molecular targets for B‐cell therapies include cell surface molecules such as CD20 (rituximab) and CD22 (epratuzumab); co‐stimulatory molecules involved in B‐cell–T‐cell interaction such as CTLA4 and B7 molecules (abatacept); maturation and growth factors such as B‐cell activating factor and a proliferation‐inducing ligand (belimumab, briobacept, atacicept) and B‐cell tolerogen (abetimus). This article provides an overview on normal B‐cell physiology and abnormal B‐cell biology in SLE that form the immunological basis of B‐cell‐targeted therapy in the treatment of these patients with refractory diseases.