SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by periods of illness and remissions in which the immune system produces antibodies to cells within the body leading to widespread inflammation and tissue damage. Immunologic abnormalities, especially the production of a number of antinuclear antibodies (ANA), are a prominent feature of the disease. SLE has a variety of clinical manifestations, and it can affect joints, skin, brain, lungs, kidneys, and blood vessels. Individuals with SLE may experience fatigue, pain or swelling in joints, skin rashes, and fevers.
On March 9, 2011, the US Food and Drug Administration (FDA) approved belimumab (Benlysta) for intravenous (IV) use, an intravenously delivered agent, for use in individuals with active, autoantibody-positive lupus (systemic lupus erythematosus [SLE]) who are receiving standard therapy, including corticosteroids, antimalarials, immunosuppressives, and nonsteroidal anti-inflammatory drugs (NSAIDs). It is the first inhibitor intended to target B-lymphocyte stimulator (BLyS) protein, which may reduce the number of abnormal B cells. BLyS is overexpressed in patients with SLE and other autoimmune diseases. After subsequent studies using the IV formulation, the FDA granted approval in pediatric individuals age five years and older. Additionally, a subcutaneous formulation of belimumab (Benlysta) for use in adults was also FDA approved.
LUPUS NEPHRITIS (LN)
Systemic Lupus Erythematosus (SLE)
Two clinical studies involving 1,684 individuals with lupus demonstrated the safety and effectiveness of belimumab (Benlysta) for IV use. The studies diagnosed individuals with active lupus and randomized them to receive belimumab (Benlysta) for IV use plus standard therapy, or an inactive infused solution (placebo) plus standard therapy. The studies excluded anyone who had received prior B-cell targeted therapy or IV cyclophosphamide, and those who had active lupus involving the kidneys or central nervous system.
The individuals treated with belimumab (Benlysta) for IV use and standard therapies experienced less disease activity than those who received a placebo and standard-of-care medicines. Results suggested, but did not definitively establish, that some patients had a reduced likelihood of severe flares, and some reduced their steroid doses.
Subsequent safety and efficacy results for subjects treated up to seven years continue to support disease control and safety profile in individuals with active SLE taking belimumab (Benlysta) plus standard therapy.
Lupus Nephritis (LN)
A clinical study involving 448 individuals with active proliferative and/or membranous LN demonstrated the safety and effectiveness of belimumab (Benlysta) for IV use. The individuals had a clincial diagnosis of SLE according to American College of Rheumatology classification criteria; biopsy-proven LN Class III, IV, and/or V; and had active renal disease at screening requiring standard therapy: corticosteroids with 1) mycophenolate for induction followed by mycophenolate for maintenance, or 2) cyclophosphamide for induction followed by azathioprine for maintenance.
The proportion of individuals achieving Primary Efficacy Renal Response (PERR) at week 104 was significantly higher in individuals receiving belimumab (Benlysta) plus standard therapy compared with placebo plus standard therapy (p=0.031). The major secondary endpoints also showed significant improvement with belimumab (Benlysta) plus standard therapy compared with placebo plus standard therapy. In descriptive subgroup analyses, the PERR and Complete Renal Response (CRR) rates were examined by induction therapy (mycophenolate or cyclophosphamide), biopsy class (Class III or IV, Class III + V or Class IV + V, or Class V), and urine protein:creatinine ratio (uPCR) levels at baseline (<3 g/g or ≥3 g/g; post-hoc analysis). In descriptive subgroup analyses of time to renal-related event or death, results were consistent with the overall endpoint regardless of induction therapy (mycophenolate or cyclophosphamide), biopsy class (Class III or IV, Class III + V or Class IV + V, or Class V; post-hoc analysis), and baseline proteinuria (<3 g/g or ≥3 g/g; post-hoc analysis). The treatment difference was primarily driven by the renal worsening and renal-related treatment failure components of the endpoint.
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