Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Belimumab (Benlysta), which recently received marketing approval, is the first of a new class of immunomodulators with a novel mechanism of action. It is a specific inhibitor of the soluble B-lymphocyte stimulator (BLyS) cytokine, which has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Two large phase III randomized controlled clinical trials evaluated the safety and efficacy of belimumab combined with standard therapy and showed that the efficacy of this treatment was significantly superior to placebo plus standard therapy. Belimumab is an evidence-based therapeutic option for patients with general lupus disease activity and may signal a shift in the existing treatment paradigm from therapeutic selection targeting specific organ involvement to an approach directed at tackling multisystem disease activity and preventing the disease from worsening.
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PMID:Belimumab: a BLyS-specific inhibitor for the treatment of systemic lupus erythematosus. 2213 Jan 21

Today corticosteroids plus hydroxychloroquine are the cornerstone in the treatment of Systemic Lupus Erythematosus (SLE). In severe cases, particularly in proliferative glomerulonephritis, cyclophosphamide or mycofenolate mofetil are used in induction and mycofenolate mofetil or azathioprine are used to maintain the remission. Corticosteroid sparing is an important goal. New and future treatments of SLE focus on B and T cells down regulation and co-stimulation, cytokine inhibition, and open the concept of immune vaccination. However, positive phase III randomized studies in SLE remain rare. Rituximab (a chimeric monoclonal anti-CD 20 antibody) was the first promising biologic agent showing interesting results in large case series but 2 phases III randomised studies didn't reach their primary objective. This probably emphasizes the limit of the current tools used for the evaluation of the disease and point out the design of the studies using high dose of corticosteroids, immunosuppressive drugs and the use of rituximab as add on treatment and are not face to face with conventional treatment. Abatacept (CTLA4-Ig) also failed to meet its primary end point in a randomised controlled trial in non-nephritis SLE. A post-hoc analysis suggests however that abatacept may be beneficial in lupus patients with arthritis however, it will probably never be approved for that indication. Belimumab (a human monoclonal antibody to BLyS) is the first biologic agent which reached its primary end point in 2 different randomised controlled trials using a new index for the evaluation of the activity of the diseases taking into account the physicians judgement (SLE responder index). Lots of phase I/II studies are currently ongoing particular targeting on interferon alpha, interleukin 6, B cell CD22 and C5 complement component.
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PMID:[What's new in internal medicine: emerging treatments for systemic lupus erythematosus]. 2220 45

Belimumab is the first biologic approved for patients with systemic lupus erythematosus (SLE). Belimumab is the first of a new class of drug targeting B cell-stimulating factors or their receptors to reach the market. Its target, BLyS, also known as BAFF (B cell-activating factor from the tumor necrosis factor family), is a type II transmembrane protein that exists in both membrane-bound and soluble forms. Additionally to a robust rational from murine experiments conducted in lupus prone mice, BLyS circulating levels are increased in SLE patients. After the negative results of a Phase II trial, two Phase III trials met their primary endpoints. Some SLE patients are still refractory to the standard options of care or necessitate prolonged high-dose corticotherapy and/or long-term immunosuppressive regimens. However, some experts still feel that the effect of this biologic might not be clinically relevant and blame the use of the new systemic lupus response index as well as the discrepancies between both trials and the noninclusion of the severe form of the disease as nephritis. In this review, we aim to discuss the characteristics of belimumab, critically evaluate the different steps of its development, and consider its future place in the arsenal against SLE, taking into account the patients' perspectives.
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PMID:New treatment options for lupus - a focus on belimumab. 2234 56

Neuropsychiatric systemic lupus erythematosus (NPSLE) is the least understood, yet perhaps the most prevalent manifestation of lupus. The pathogenesis of NPSLE is multifactorial and involves various inflammatory cytokines, autoantibodies, and immune complexes resulting in vasculopathic, cytotoxic and autoantibody-mediated neuronal injury. The management of NPSLE is multimodal and has not been subjected to rigorous study. Different treatment regimens include nonsteroidal anti-inflammatory drugs, anticoagulation, and immunosuppressives such as cyclophosphamide, azathioprine, mycophenolate mofetil, and methotrexate. For refractory NPSLE, intravenous immunoglobulin (IVIG), plasmapheresis, and rituximab have been used. Adjunctive symptomatic treatment complements these therapies by targeting mood disorders, psychosis, cognitive impairment, seizures or headaches. Several new biological agents are being tested including Belimumab, a human monoclonal antibody that targets B lymphocyte stimulator. This review focuses on the pathophysiology, treatment, and new potential therapies for neuropsychiatric manifestations of systemic lupus erythematosus.
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PMID:Neuropsychiatric systemic lupus erythematosus. 2237 59

In November 2009, Human Genome Sciences and Glaxo-Smith Kline [HGS (Rockville, Maryland) and GSK, respectively] announced that Belimumab, a neutralizing antibody to the tumour necrosis factor (TNF)-like ligand, B-cell activating factor (BAFF belonging to the TNF family, also named BLyS), met the primary endpoints in two phase III clinical trials in systemic lupus erythematosus (SLE, lupus). In March 2011, Belimumab was approved by the US Federal Drug Agency for treatment of SLE patients; this was followed in May with approval by the European Medicines Agency for use in the European Union. This is an exciting development as it is the first successful late-stage clinical trial in SLE in over 40 years. In the light of this breakthrough, we review the key data and research outcomes and examine how blocking BAFF in patients with SLE significantly improves clinical outcomes.
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PMID:BAFF/BLyS inhibitors: A new prospect for treatment of systemic lupus erythematosus. 2264 24

Systemic lupus erythematosus is a multisystem autoimmune disease characterized by the formation of autoantibodies that target a variety of self antigens. B cells are fundamental to the development of these antibodies and are a target for intervention in the disease. This review discusses four therapies that target B cells by inducing B-cell depletion, reduction in B-cell proliferation and differentiation, or modulation of B-cell function. Rituximab is an anti-CD20 chimeric monoclonal antibody that depletes B cells but not plasma cells. Systematic reviews of open label studies, particularly in lupus patients refractory to conventional therapy, have suggested that rituximab can be an effective treatment for non-renal lupus and lupus nephritis. However, randomized, double-blind, controlled trials comparing rituximab with placebo in addition to standard of care therapy for non-renal lupus and lupus nephritis over 12 months failed to demonstrate efficacy using the planned primary endpoints, although there were some post-hoc analyses suggesting that rituximab may have beneficial effects that would be worthy of further study as no significant toxicity has been demonstrated. Treatment with belimumab, a humanized monoclonal antibody targeted against B lymphocyte stimulator (BLys), was more efficacious than placebo and had no significant increase in adverse events in two non-renal, phase III lupus trials when given in addition to standard of care therapy for 52 weeks. Belimumab is licensed for the management of lupus in the US and in Europe. Atacicept is a humanized fusion protein that binds BLys and APRIL (a proliferation-inducing ligand) that might be more effective than belimumab in the management of lupus. Unfortunately a phase II/III trial of atacicept in lupus nephritis had to be stopped due to the development of low immunoglobulin levels and pneumonias in some patients. However, in retrospect these complications may have been due to concomitant treatment with mycophenolate mofetil and results of a 52-week, non-renal, phase III trial with atacicept are awaited. Epratuzumab is a humanized monoclonal antibody that targets CD22 on B cells and results in modulation of B-cell function and migration, as CD22 regulates adhesion and inhibits B-cell receptor (BCR) signalling. Epratuzumab at a cumulative dose of 2,400 mg over 4 weeks has been shown to improve lupus disease activity compared with placebo 12 weeks after initiation of therapy in a phase II study, and a 12-month phase III study is on-going. B-cell targeted therapies are an attractive prospect for treating lupus disease and the results of current phase III trials are eagerly awaited. Finding the most appropriate trial design to demonstrate efficacy in lupus trials has been a challenge. The SRI (SLE response index) used in the belimumab studies and the BICLA (British Isles Lupus Assessment Group-based Composite Lupus Assessment) used in the epratuzumab studies are currently the promising trial designs for non-renal studies. For lupus nephritis it is important that trials are of adequate duration to be able to demonstrate benefit of new therapies over conventional therapy.
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PMID:B-cell targeted therapies in systemic lupus erythematosus: successes and challenges. 2345 53

B lymphocyte stimulator (BLyS), a protein discovered in the 1990s that induces B cell proliferation and differentiation, promotes B cell survival, and is important in immunoglobulin class switching, was the target of a drug development program launched by Human Genome Sciences in the early part of the last decade. Belimumab, a human monoclonal antibody specific for soluble BLyS, was ultimately approved by the United States Food and Drug Administration (FDA) in March 2011 for active autoantibody patients with systemic lupus erythematosus (SLE) despite standard therapy. This program, whose studies spanned approximately 10 years from phase I through phase III, was founded on sound biology and advanced on logic and perseverance. Pre-clinical experimentation in murine models of SLE as well as observational studies in human SLE provided sufficient evidence to support the use of an inhibitor of BLyS as a novel therapy to reduce SLE disease activity. Progressing from phase I through a robust phase III program was no easy task given the complexities of SLE trial design. These challenges were overcome with the implementation of strict study entry requirements, the development of a novel responder index, and rigorous rules regarding background therapies. The success of two phase III studies and the approval of belimumab by the US Food and Drug Administration represent an unprecedented milestone in the history of SLE drug development. Belimumab was the first drug approved in SLE in over 50 years and was the first drug ever approved in SLE through the conventional route of randomized controlled trials. This article reviews the biology of BLyS, clinical trial results, and some of the emerging data from the robust phase II and III datasets.
Lupus 2013 Apr
PMID:Breaking the ice in systemic lupus erythematosus: belimumab, a promising new therapy. 2355 79

Systemic lupus erythematosus (SLE) is a complex heterogeneous disease, posing challenges to clinical trials. As in other autoimmune diseases, B-lymphocytes play a central role in lupus pathogenesis. The finding that selection and survival of B cells are controlled by a variety of signals, including those provided by the longevity factor BAFF (B-cell activating factor), also called BLyS (B-lymphocyte stimulator), led to preclinical trials that revealed that BAFF represents a promising therapeutic target for human lupus. Belimumab is a fully human monoclonal antibody directed against BAFF. Lessons learned from early clinical trials led to improved methods and success of phase III trials, with recruitment of patients with both clinically and serologically active disease, development and use of a novel SLE Responder Index, and progressive and special restrictions on immunosuppressive and corticosteroid use. These studies offer an attractive blueprint to conduct future clinical trials in SLE. The overall steroid-sparing ability and benefits of belimumab on musculoskeletal and mucocutaneous organ systems suggest that it has an impact on the clinical management of SLE patients. Future directions include studies to determine the role of belimumab in early SLE, as well as in renal or CNS involvement.
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PMID:Belimumab therapy in systemic lupus erythematosus. 2356 79

We report the case of a 19-year-old woman with progressive proliferative lupus nephritis (LN) class III after induction and maintenance therapy with mycophenolate mofetil (MMF). Despite a satisfying clinical improvement proteinuria progressed under this medication. We treated the patient with additional belimumab after discussing other options. Following treatment with belimumab, proteinuria rapidly improved to almost normal levels and clinical remission lasted. Belimumab might hold promise for this indication.
Lupus 2013 Dec
PMID:Successful treatment of a mycophenolate mofetil-refractory proliferative lupus nephritis with Belimumab in a 19-year-old woman. 2401 69

The efficacy and safety of targeted biological therapies have been analyzed in patients suffering from systemic lupus erythematosus. In renal lupus, infliximab has shown prolonged improvement of the renal function after the induction period (small open studies), whereas abatacept had no significant efficacy (randomised controlled study). In renal and non renal lupus, rituximab did not confirm its efficacy in two randomised controlled studies. In non renal lupus, epratuzumab has shown efficacy in a phase IIb. Belimumab at the high posology of 10 mg/kg has also shown significant efficacy in two large randomised controlled studies.
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PMID:[The management of systemic lupus erythematosus with biological therapies]. 2402 19


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