Study BEL115123 is a randomized, placebo-controlled, double-blind, multinational study of belimumab (10 mg/kg) to investigate the efficacy and safety of belimumab in subjects with MG. The study will enroll male and female outpatients (\> or equal to 18 years of age) with a diagnosis of MG who are 1) acetylcholine receptor (AChR) antibody positive or muscle specific kinase (MuSK) antibody positive, 2) on current standard of care therapy, and 3) continue to exhibit signs of MG. The study will include 3 phases: a 4 week screening period, a 24 week treatment period, and a 12 week follow-up period. IP will be administered intravenously on Days 0, 14, 28 and then every 28 days through and including Week 20. At Week 24, primary outcomes will be obtained. Follow up evaluations will be conducted at Weeks 28, 32 and 36 for all subjects. The primary objective of this study is to assess the efficacy of belimumab as evaluated by the change in the quantitative myasthenia gravis (QMG) score.

The investigators propose to perform RNA-sequencing of the whole blood initially, in a cohort of 80 SLE patients who will receive belimumab as part of standard clinical practice, in order to assess intra-patient longitudinal (baseline, 1, 3 and 6 months) transcriptome changes and examine whether treatment can ameliorate the activity/flare, severity and major organ disease gene signatures. The investigators will also obtain preliminary information on molecular signatures predicting clinical responses and the impact of belimumab on gene signatures of host defense against viral and bacterial (including mycobacterial) pathogens. Using modules of cell type-specific genes and co-expression gene networks, The investigators will deconvolute our data to define pertinent molecular alterations in specific immune cell types. Results will be validated and functionally characterized by single-cell mass cytometry (performed at the aforementioned time points), which enables investigation of the cell identity (including subsets of B-cells and myeloid cells of particular relevance to the disease) and activation status at protein level (e.g. phosphorylation) through next-generation, high-dimensional flow cytometry. Through a focused analysis followed by targeted gene expression and function studies in purified monocytes, the investigators will determine whether belimumab can restore \"SLE-primed\" monocytes thus, alleviating their inflammatory and pro-atherogenic phenotype and enhancing their bactericidal activity. Collectively, these studies will provide novel mechanistic insights on the beneficial efficacy/toxicity ratio of belimumab therapy in SLE.

This study is a phase II trial of belimumab in combination with rituximab/venetoclax in patients with refractory or relapsed chronic lymphocytic leukemia (CLL). Treatment of CLL has drastically changed in the past years as new therapeutic agents have gained clinical approval. The combination rituximab/venetoclax over a course of two years is approved as second line therapy especially in patients with high risk CLL (del17p), showing high remission rates and achievement of MRD (minimal residual disease) negativity. The next goals in CLL therapy are now to increase the rate of MRD negativity and to achieve an earlier MRD negativity during the course of treatment to allow for a reduction of treatment time and therefore treatment-induced toxicities. In line with other hematologic diseases, progression free survival depends on remission status, especially MRD negativity, after last treatment as MRD positivity after therapy indicates the persistence of treatment resistant CLL cells. One mechanism of therapy resistance has been described as reduced sensitivity to rituximab-induced antibody dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) cell production of B-lymphocyte stimulator (BlyS, also called BAFF), which can be bound by belimumab, a human anti-BAFF antibody. Moreover, recombinant human (rh)BAFF can dose dependently reverse cytotoxic effects of venetoclax, which could also be restored by the application of belimumab. This led to the conceptualization of this clinical trial, in which belimumab is applied as a weekly subcutaneous injection in combination with standardrituximab/venetoclax treatment for up to 24 months in relapsed and refractory CLL patients. By removing BAFF from the CLL microenvironment we aim to increase the efficacy of rituximab/venetoclax treatment to achieve higher and earlier MRD negativity rates and allow for an abbreviated treatment.

To investigate the efficacy of belimumab in early SLE patients (disease duration less than 6 months).

INTRODUCTION:

Childhood systemic lupus erythematosus (cSLE) is a complex multisystem autoimmune disease. In 2019, belimumab was approved for the clinical treatment for cSLE, making it the only biological agent approved for cSLE children aged 5 and older in 60 years.

OBJECTIVE:

To review emerging evidence on belimumab in cSLE published up to April 2022, so as to provide information for clinical decision-making.

METHOD:

A comprehensive search of relevant publications up to the date of April 2022 in PUBMED, EMBASE, WOS, COCHRANE, ClinicalTrials.gov, CBM, CNKI and WANFANG was performed using the following criteria: (a) English and Chinese language studies; (b) RCT studies, cohort studies, or case-control studies; (c) patients with age <18; (d) Observational studies or case series studies contain more than 5 patients. All relevant literature was independently screened and reviewed by at least two reviewers and the obtained literature data were extracted and reviewed by two authors.

RESULTS:

Five publications met the inclusion/exclusion criteria for c

SLE:

one randomized controlled trial, one retrospective cohort study, and three case series. There was a high degree of heterogeneity among several studies, and the availability of baseline and outcome data provided was uneven.

CONCLUSION:

At present, there is a lack of high-quality clinical trials of belimumab in the treatment of cSLE. Based on the current research, it is believed that the use of belimumab can inhibit cSLE activity, reduce the dose of corticosteroids and immunosuppressants, and delay kidney damage. Also it shows clinical benefit in alleviating symptoms of monogenic cSLE refractory to standard therapy. More studies are urgently needed to validate the clinical efficacy of belimumab in cSLE and to evaluate its long-term safety in pediatric populations to promote evidence-based practice.

There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: nonsteroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxychloroquine for mild disease, and broad spectrum immunosuppressants plus antiinflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity. Drug metabolism and clearance may be severely compromised. Therefore, it is a priority to develop better treatments with fewer adverse events that can be used at different stages of disease activity. In recent years, a member of the tumor necrosis factor (TNF) family, soluble human B Lymphocyte Stimulator protein (BLyS), also referred to as B-cell activating factor (BAFF) and TNFSF13B has been studied extensively. This protein is synthesized by myeloid cell lines, specifically interacts with B lymphocytes and increases their life-span. BlyS plays a key role in the selection, maturation and survival of B cells and it has a significant role in the pathogenesis of SLE. In this review, we analyzed the role of BLyS as a diagnostic/prognostic marker and/or therapeutic target for lupus patients, and the different clinical studies published using belimumab.

There is a vital role of B cells in the pathogenesis of Systemic Lupus Erythematosus (SLE). Belimumab (Bel), an inhibitor of B cell activating factor (BAFF), and Rituximab (RTX), a monoclonal antibody targeting Cd20 antigen, have been used to manage systemic lupus. Several randomized controlled trials (RCTs) have evaluated these two agents' clinical efficacy and safety in different manifestations of SLE. This study aims to review the randomized control trials involving these two agents systematically and to explain if any disparity is noticed in the primary and secondary outcomes between these two agents. This study is done according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After applying the inclusion criteria and quality assessment by independent reviewers and co-authors, relevant papers were identified, and data were extracted. The results have shown that RCTs involving Belimumab achieved primary endpoints; however, targeted endpoints were not achieved in studies involving Rituximab. It is concluded that despite the conflicting results obtained in clinical trials, both are effective in systemic lupus, as indicated in real-world clinical experience. However, better-designed multicenter studies evaluating these B-cell-targeting drugs are needed.

This global Belimumab Pregnancy Registry will collect prospective data on pregnancies and pregnancy outcomes on a voluntary basis in women with systemic lupus erythematosus (SLE) who have received commercially supplied belimumab within the 4 months prior to and/or during pregnancy. The registry will also evaluate outcomes of infants born to mothers who were exposed to belimumab within the 4 months prior to and/or during pregnancy. This registry will add to the current clinical experience with belimumab and will complement reproductive data from animal toxicology studies. It will also assist clinicians in weighing the potential risks against the benefits of treatment for individual patients with SLE. GlaxoSmithKline (GSK) will sponsor the Belimumab Pregnancy Registry in countries where it holds Marketing Authorization.

The BeliLES-GEAS project pretends to obtain an extensive data registry of patients with systemic lupus erythematosus (SLE).

The main objective is to create a national SLE patients registry treated with belimumab to describe effectiveness and safety of intravenous (IV) or subcutaneous (SC) belimumab in patients with active SLE treated in the Spanish departments of Internal Medicine in a real-life setting. This research project aspires to cover the vast majority (if not the whole) of SLE patients treated with belimumab in all of the Spanish Departments of Internal Medicine.

GlaxoSmithKline (GSK) have submitted a Biologic License Application (BLA) for the subcutaneous formulation of belimumab which is currently under review by the Food and Drug Administration (FDA). The goal of this individual patient compassionate use supply is to provide a patient with subcutaneous belimumab for the period of 1 year or until the subcutaneous formulation of belimumab becomes approved for use by the FDA and is commercially available to this patient, whichever is sooner. You can access GSK\'s Policy on Compassionate via http://www.gsk.com/media/3368/compassionate-use.pdf.