Belimumab and the clinical data.

Benlysta (belimumab) is a fully human recombinant monoclonal IgG antibody that neutralizes soluble B-lymphocyte stimulator and inhibits its biologic activity. Benlysta was recently approved by the US Food and Drug Administration to treat systemic lupus erythematosus (SLE). The current review discusses the data from the belimumab clinical trials and the role of this new medication in the treatment of SLE. We propose that Benlysta should be used in antinuclear antibody-positive patients with active disease in whom the goal of therapy is to decrease SLE activity, reduce flares, and help lower background medications. With this being the first drug approved for treatment of SLE in 50 years, patients have more treatment options, while researchers have a greater understanding of SLE and clinical trial design in such a heterogeneous disease.

Systemic lupus erythematosus: an overview.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology in which the normal immune responses are directed against healthy organs and tissues. The disregulated immune system produces antibodies that attack the skin, joints, kidneys, heart, and brain. Some people experience mild rashes and arthritis, others suffer debilitating fever, fatigue, joint pain, and severe organ and/or life-threatening disease. This article provides a medical overview of the epidemiology of SLE, the challenges of diagnosing SLE, the complexity of the clinical manifestations and treatment issues, and the impact of SLE on patients' lives. We also discuss the progress in understanding the disease and its therapy over the last century.

Treatment of lupus nephritis.

The treatment of lupus nephritis has evolved over the past few decades. Standard practice is to define the first 6 months of therapy as an induction phase, during which the goal of therapy is to achieve renal remission, usually with bolus intravenous infusions of the cytotoxic cyclophosphamide or the immunosuppressant mycophenolate mofetil (MMF). Following induction, therapy is continued, with some decrease in aggressive dosing for a more prolonged period of time-typically 24 months-that is aimed at preventing renal flares and smoldering disease, which could lead to continuous deterioration of renal function. During maintenance, the usual therapeutic option is immunosuppression with MMF or azathioprine. In recent years, MMF has been increasingly replacing intravenous cyclophosphamide as an initial standard of care. The current paper reviews data on these treatment strategies and suggests a possible treatment algorithm for clinical care.

Preliminary test of the LFA rapid evaluation of activity in lupus (LFA-REAL): an efficient outcome measure correlates with validated instruments.

OBJECTIVE: Current disease activity measures for systemic lupus erythematosus (SLE) are difficult to score or interpret and problematic for use in clinical practice. Lupus Foundation of America (LFA)-Rapid Evaluation of Activity in Lupus (REAL) is a pilot application composed of anchored visual analogue scores (0-100 mm each) for each organ affected by lupus. This study evaluated the use of LFA-REAL in capturing SLE disease activity. METHODS: In a preliminary test of LFA-REAL, this simplified, organ-based system was compared with the most widely used outcome measures in clinical trials, the British Isles Lupus Assessment Group 2004 Index (BILAG), the SLE Disease Activity Index (SLEDAI) and the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI Physician's Global Assessment (SS-PGA). The level of agreement was analysed using Spearman rank correlations. RESULTS: 91 patients with SLE with mild to severe disease activity were evaluated, their median SLEDAI score was 4.0 (range 0-28) and BILAG score 8.0 (0-32). The median SS-PGA was 38 mm (4-92) versus the total REAL 50 mm (0-268), which expands in range by additive organ scores. Thirty-three patients had moderate to severe disease activity (≥1.5 on SS-PGA landmarks). The median SS-PGA score of this group was 66 mm (50-92) versus median REAL score of 100 mm (59-268), confirming ability to detect a wider distribution of scores at higher disease activity. Total REAL correlated with SLEDAI, BILAG and SS-PGA (correlation coefficient=0.816, 0.933 and 0.903, respectively; p<0.001 for all). Individual LFA-REAL organ scores for musculoskeletal and mucocutaneous also correlated with corresponding BILAG domain scores (correlation coefficient=0.925 and 0.934, p<0.001). CONCLUSIONS: In this preliminary exercise, there were strong correlations between LFA-REAL and validated lupus disease activity indices. Further development may be valuable for consistent scoring in clinical trials, grading optimal assessment of change in disease activity and reliable monitoring of patients in practice.

Biological performance of biodegradable amino acid-based poly(ester amide)s: Endothelial cell adhesion and inflammation in vitro.

Functionalized amino-acid-based poly(ester-amide)s (PEA) are a new family of synthetic biodegradable polymers consisting of three naturally occurring building blocks (amino acids, diols, and dicarboxylic acids) that have been suggested to be promising biomaterials for therapeutic use. However, little is known about their cytotoxicity, ability to support cell growth, inflammatory properties, or mechanical properties, key aspects to most biomaterials designed for in vivo implantation and tissue engineering applications. In this study, we investigated the ability of two functionalized PEA materials (amino-functionalized and carboxylic acid functionalized) and a neutral PEA control to support endothelial cell viability, proliferation, and adhesion. Additionally, we investigated the inflammatory response elicited by these functionalized PEA materials using a macrophage cell model. Our results indicate that all forms of PEA were noncytotoxic and noninflammatory in vitro. The amino-functionalized PEA bests supports endothelial cell adhesion, growth, and monolayer formation. Mechanical testing indicates that the elastic moduli of these materials are strongly dependent on the charge formulation, but do exhibit linearly elastic behavior at small strains (<10%). Our data suggest that PEA may be a viable biomaterial for use in tissue engineering applications, particularly for use as a vascular graft.