Benlysta (belimumab) / GSK - LARVOL DELTA

Aged B cells as a candidate cell of origin for diffuse large B cell lymphoma: A multi-modal analysis of somatic mutation, clonality, and transcriptional programs (ASH 2025) - "To establish a biological connection between ABCsand DLBCL, we analyzed paired blood and tumor samples to identify shared mutations and CDR3 clones.Longitudinal immune monitoring in autoimmune patients treated with biologic agents (adalimumab,belimumab, etanercept) was used to assess treatment-related changes in ABC dynamics. Our findings implicate ABCs as a likely reservoir of lymphoma-initiating clones and a candidate cell oforigin for DLBCL. The enrichment of AID-driven mutations, clonal dominance, and overlapping betweenABC and tumor clones supports a model in which aberrant persistence and ongoing mutagenesis in ABCspromote lymphomagenesis. This work establishes a framework for mutation-informed MRD surveillanceand highlights the clinical relevance of ABC biology across both AI and B cell malignancy."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • AICDA • ARID1A • CD14 • ITGAX • ITGB2 • KMT2D • PRDM1 • ZEB2

P048 Lenalidomide use in recalcitrant inflammatory dermatoses: a trio of successes. (PubMed, Br J Dermatol) - "A 36-year-old woman with recurrent aphthous stomatitis had not responded to treatment with colchicine, pentoxifylline, azathioprine, dapsone or mycophenolate mofetil...A 49-year-old woman with severe recalcitrant cutaneous discoid lupus erythematosus (CDLE), systemic lupus and Raynaud phenomenon with chilblains had not responded to, had intolerance to or had adverse side-effects with multiple systemic agents including hydroxychloroquine, mepacrine, dapsone, rituximab biosimilar, mycophenolate mofetil, fumaric acid esters, acitretin, ciclosporin, thalidomide (tremor/loss of concentration), belimumab and methotrexate...Baseline and renal function monitoring is required for dose adjustment, and strict adherence to pregnancy prevention programmes is necessitated due to teratogenicity. Our three cases demonstrate lenalidomide to be a clinically beneficial, fast-acting and well-tolerated alternative off-label option for recalcitrant inflammatory dermatoses."

Journal • Cardiovascular • Cataract • Dental Disorders • Dermatology • Discoid Lupus Erythematosus • Hematological Disorders • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Movement Disorders • Multiple Myeloma • Myelodysplastic Syndrome • Neutropenia • Oncology • Ophthalmology • Pain • Peripheral Neuropathic Pain • Rheumatology • Stomatitis • Systemic Lupus Erythematosus • Thrombocytopenia • IL12A • IL6

A Study of GSK4527363 in Healthy Participants, Systemic Lupus Erythematosus (SLE) Participants and Healthy Chinese and Japanese Participants (clinicaltrials.gov) - P1 | N=142 | Recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Jun 2027 ➔ Jan 2028 | Trial primary completion date: Jun 2027 ➔ Jan 2028

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

BTLA-Expressing Memory B Cells Are Associated with Belimumab-Induced Improvement in Systemic Lupus Erythematosus. (PubMed, Int J Mol Sci) - "To validate these findings, we plan to further assess the effects of belimumab on BTLA expression and B cell signaling pathways in treatment-naive patients with SLE by western blotting. Collectively, our results provide a novel foundation for establish appropriate belimumab administration criteria."

Journal • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • BTLA • PLCG2

Systemic Lupus Erythematosus: Ophthalmological Safety Considerations of Emerging and Conventional Therapeutic Agents. (PubMed, Int J Mol Sci) - "With the advent of targeted immunomodulatory agents, the therapeutic landscape of SLE has expanded beyond conventional drugs such as hydroxychloroquine and corticosteroids toward biologics and small molecules designed to interfere with specific immunological pathways...In contrast, recently approved or investigational therapies-such as belimumab, anifrolumab, voclosporin, dual BAFF/APRIL inhibitors, rituximab, JAK inhibitors, CD40/CD40L blockade, CD38 inhibition, and mesenchymal stromal cell-based strategies-have limited but evolving safety data, with potential ocular adverse events spanning inflammatory, vascular, neuro-ophthalmic, and structural domains...These findings highlight the need for systematic ophthalmological surveillance in patients receiving immunomodulatory therapies for SLE. Early recognition and timely management of ocular toxicity are crucial to safeguarding visual function and optimizing long-term therapeutic outcomes in this vulnerable patient..."

Journal • Review • Cataract • Glaucoma • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Ophthalmology • Retinal Disorders • Systemic Lupus Erythematosus • CD40LG

Update on cutaneous lupus erythematosus pathogenesis, diagnosis and management. (PubMed, J Eur Acad Dermatol Venereol) - "Antimalarials, particularly hydroxychloroquine, remain the cornerstone of systemic therapy. Second-line or third-line agents such as methotrexate, retinoids, dapsone, thalidomide and lenalidomide are recommended in refractory cases. Biological therapies, including belimumab and anifrolumab, are approved in the setting of SLE. Promising results from recent trials of targeted therapies including inhibitors of plasmacytoid dendritic cells, TLR7/8 and TYK2 are paving the way for novel treatment strategies in CLE."

Journal • Review • Cutaneous Lupus Erythematosus • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • TLR7 • TYK2

Indirect comparative efficacy and safety of belimumab vs. anifrolumab in systemic lupus erythematosus and lupus nephritis: a meta-analysis of randomized trials. (PubMed, Z Rheumatol) - "Belimumab confers greater benefit in terms of SRI‑4 response for SLE, while anifrolumab is more effective for corticosteroid tapering and immunologic parameter normalization. In LN, the comparative efficacy remains uncertain. Both agents exhibit similar safety profiles, but anifrolumab is associated with an increased risk of herpes zoster. Differences in study design, inclusion criteria, and assessment protocols among included trials may limit direct comparability."

Journal • Retrospective data • Glomerulonephritis • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus • Varicella Zoster

A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE) (clinicaltrials.gov) - P3 | N=514 | Recruiting | Sponsor: GlaxoSmithKline | N=225 ➔ 514 | Trial primary completion date: Jul 2028 ➔ Dec 2029

Enrollment change • Trial primary completion date • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

Efficacy and Safety of Belimumab in Patients with Lupus Nephritis Complicated with End-stage Renal Disease (Frontiers) - "This study analyzed data from eight ESRD-LN patients treated with belimumab over a median follow-up period of 28.01 ± 14.57 months. Belimumab significantly reduced extra-renal SLEDAI scores (from 6.13 ± 3.09 to 1.50 ± 1.41, p<0.01) and improved complement C3 levels (from 0.64 ± 0.12 g/L to 0.8 ± 0.16 g/L). Prednisone Glucocorticoids dosages were markedly decreased (from 21.25 ± 9.64 mg/day to 3.91±3.98 mg/day), with three patients discontinuing glucocorticoid therapy entirely. Mild infections were observed, but no severe infections requiring mechanical ventilation occurred."

Clinical data • Lupus Nephritis

CD19/BCMA CAR-T Cell Therapy for Refractory Systemic Lupus Erythematosus - Safety and Preliminary Efficacy Data from a Phase I Clinical Study (ASH 2023) - "After lymphodepleting chemotherapy with cyclophosphamide/fludarabine (D-4 to D-2), patients receive a single infusion of 1-2x106 CD19 CAR-T cells and BCMA CAR-T cells per kilogram of body weight at D0...All patients had active severe SLE and had received glucocorticoids, hydroxychloroquine, tacrolimus, total glucosides of paeony, merti-macrolide, leflunomide, azathioprine, methotrexate, cyclophosphamide, immunoglobulin, rituximab, belimumab, and Tetracycline before treatment with CAR-T cells, which were standard treatments that were either ineffective or difficult to withdraw.3 patients received 1x10^6/kg of each of CD19 CAR-T cells and BCMA CAR-T cells, and 9 patients received 2x10^6/kg of each of CD19 CAR-T cells and BCMA CAR-T cells 2x10^6/kg... These data suggest that CD19/BCMA CAR-T cell therapy is well tolerated and can induce rapid and durable remission in severe refractory SLE."

CAR T-Cell Therapy • Clinical • P1 data • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases • Systemic Lupus Erythematosus

Beyond systemic lupus erythematosus: a systematic review on the use of belimumab in other connective tissue diseases and vasculitides. (PubMed, Clin Rheumatol) - "The SLR showed that data on the use of belimumab in rheumatic conditions, other than SLE, are still scarce. However, belimumab may have therapeutic potential in specific subsets of patients with rheumatic diseases characterized by aberrant B cell activation. Future research should focus on large, randomized phase 3 trials with extended follow-up to better define the role of belimumab in rheumatic diseases beyond SLE, particularly in combination with standard-of-care therapies."

Journal • Review • Immunology • Inflammatory Arthritis • Lupus • Rheumatology • Systemic Lupus Erythematosus • Vasculitis

A real-world safety analysis of infection-related adverse events associated with belimumab, rituximab, and TNF inhibitors using the FAERS database. (PubMed, Sci Rep) - "Results Belimumab and rituximab are more likely to cause progressive multifocal leukoencephalopathy (PML), while infliximab show a greater variety tuberculosis (TB)-related AEs than other biological agents. Clinicians should prioritize monitoring for severe events like PML, TB, and hepatitis B viral reactivation. However, epidemiological investigations and further causality assessments are required."

Adverse events • Journal • Real-world evidence • Chikungunya • CNS Disorders • Dengue Fever • Dermatology • Hepatitis B • Infectious Disease • Inflammation • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Septic Shock • Tuberculosis

Using a multi-institutional pediatric learning health system to characterize induction therapy for incident lupus nephritis in children. (PubMed, Pediatr Nephrol) - "We utilized a validated, sensitive and specific computable phenotype to identify children and adolescents with LN and subsequently characterize their induction therapy regimens, a critical first step in designing future pragmatic clinical trials."

Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Pediatrics • Renal Disease • Systemic Lupus Erythematosus

Initial Report of Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in Autoimmune Cytopenias: The RUBY-4 Study (ASH 2023) - P1/2 | "Patients with ITP or AIHA have elevated serum BAFF and APRIL levels and belimumab, a BAFF inhibitor, has exhibited encouraging efficacy in the treatment of lupus-associated ITP as well as alone or in combination with rituximab for the treatment of primary ITP. To our knowledge, povetacicept is the first dual BAFF/APRIL inhibitor to be evaluated for the treatment of autoimmune cytopenias. Previous preclinical and healthy volunteer studies suggest the potential of povetacicept for suppression of the pathogenic autoimmunity that mediates platelet/erythrocyte destruction in ITP, wAIHA, and CAD, which may lead to more durable responses and improved outcomes for patients."

Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Inflammatory Arthritis • Lupus • Thrombocytopenia • Thrombocytopenic Purpura

Povetacicept (ALPN-303), a Potent Dual BAFF/APRIL Antagonist in Development for the Treatment of Autoimmune Cytopenias, Suppresses Disease in a Mouse Model of Autoimmune Hemolytic Anemia (ASH 2023) - P1/2 | "Belimumab, an anti-BAFF antibody, has demonstrated encouraging efficacy in the treatment of ITP associated with systemic lupus erythematosus [De Marchi, et al. , Clin Exp Rheumatol, 2017] and in combination with rituximab in patients with ITP [Mahévas, et al... Povetacicept effectively reduced pathogenic autoantibodies and key B cell populations (e. g. , ASC) and limited serum LDH elevations in this mouse model of erythrocyte autoimmunity."

Preclinical • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • Thrombocytopenia • Thrombocytopenic Purpura

Belimumab combined with mycophenolate mofetil in a child with frequently relapsing, steroid-dependent nephrotic syndrome. (PubMed, Pediatr Nephrol) - "Rituximab, a B-cell-depleting agent, is effective and widely used for FRNS/SDNS, but its use can be limited by rare, serious adverse effects. This case suggests that belimumab combined with MMF is effective for refractory NS. However, as a single case report, its efficacy requires further strengthening through more cases."

Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Pediatrics • Renal Disease • Systemic Lupus Erythematosus

A Case of Novel Combination Therapy for Refractory Lupus Nephritis (KIDNEY WEEK 2025) - "She was treated with mycophenolate mofetil (MMF), hydroxychloroquine, and prednisone but required frequent steroids for persistent symptoms and serologic activity. She had an allergic reaction to rituximab and no response to 14 months of belimumab...She received six months of cyclophosphamide, with ocrelizumab later added due to poor response...Discussion In patients with LN who have suboptimal response to MMF/cyclophosphamide and prednisone, current literature recommends addition of voclosporin if high proteinuria or belimumab if prior flares...Belimumab therapy is known to have good serological and extrarenal outcomes (BLISS-LN). Our patient did not respond to either therapies individually with MMF and steroid; however, the novel combination of both achieved both clinical and serological remission for the first time in her 10 years of complicated SLE and LN history."

Clinical • Combination therapy • Acute Kidney Injury • Cardiovascular • Glomerulonephritis • Hypertension • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Systemic Lupus Erythematosus • Vasculitis

Rare Case of Podocyte Infolding Glomerulopathy in a Patient with Systemic Lupus Erythematosus (KIDNEY WEEK 2025) - "Case Description A 45-year-old female with longstanding SLE [complicated by leukopenia, thrombocytopenia, pericarditis] treated with mycophenolate mofetil, SC belimumab, hydroxychloroquine, and prednisone presented with non-oliguric AKI with concern for nephritic pattern of glomerular injury...In addition to her ongoing SLE treatment, intravenous rituximab [2 doses of 1g two weeks apart] was administered...PIG has relatively good outcomes following immunosuppression. Further investigation is warranted into its pathogenesis, clinical significance, and optimal management."

Clinical • Cardiovascular • Glomerulonephritis • Hematological Disorders • Immunology • Inflammatory Arthritis • Leukopenia • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Systemic Lupus Erythematosus • Thrombocytopenia

Successful autologous CD19 CAR T cell therapy following severe lupus flare during immunosuppressive washout in refractory lupus nephritis. (PubMed, Lupus Sci Med) - "This case report illustrates that targeted pulse corticosteroids during CAR T cell therapy washout can effectively manage severe lupus flares without impairing therapeutic efficacy."

Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Rheumatology • Systemic Lupus Erythematosus

Belimumab modulates type I interferon signalling in the treatment of systemic lupus erythematosus. (PubMed, Clin Exp Rheumatol) - "These results revealed a novel mechanism of belimumab action, advancing our understanding of the immune atlas in SLE patients before and after belimumab-targeting treatment."

Journal • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Effects of telitacicept and belimumab on systemic lupus erythematosus: a systematic review and meta-analysis. (PubMed, Sci Rep) - "Secondary outcomes included prednisone dose reduction, anti-dsDNA change, adverse events (AEs) and serious AEs. Dual inhibition of BLyS and APRIL by telitacicept may offer an effective option for reducing SLE activity. Further large-scale, long-term head-to-head trials are needed to confirm these findings."

Journal • Retrospective data • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Efficacy of adding belimumab to hydroxychloroquine for patients with serologically active clinically quiescent in systemic lupus erythematosus: A retrospective study. (PubMed, Lupus) - "The primary outcome, time-to-event achievement to reduce PSL dose to 7.5 mg/day and 5 mg/day had an HR value of 1.21 (95% confidence interval (CI) 0.78-1.89, p = 0.396) and 1.19 (95% CI 0.74-1.89, p = 0.471) in the two groups, respectively, with no significant difference between the two groups. No significant differences were observed in other outcomes.ConclusionsAdding BLM to HCQ in patients in the SACQ state did not demonstrate effects in preventing flares or reducing glucocorticoids (GC) dose."

Journal • Retrospective data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Clinical efficacy and short-term prognosis of belimumab in the treatment of systemic lupus erythematosus in children. (PubMed, Am J Transl Res) - "Conventional glucocorticoid therapy combined with belimumab effectively enhances treatment outcomes in pediatric SLE patients, reduces the risk of short-term recurrence, and does not increase adverse reactions."

Journal • Immunology • Inflammatory Arthritis • Lupus • Pediatrics • Systemic Lupus Erythematosus • CRP

A Rare Case of Lupus Nephritis in a Patient with Ulcerative Colitis (KIDNEY WEEK 2025) - "IgG subclass staining showed IgG1 and IgG2 predominance, consistent with LN class V. The patient was treated with hydroxychloroquine 200 mg/day, prednisolone 30 mg/day, and tacrolimus 3 mg/day...Therefore, the treatment regimen was augmented with mycophenolate mofetil (200 mg/day) and belimumab (200 mg/week)...Although the possibility of mesalazine-induced LN cannot be entirely excluded, the patient's nephropathy demonstrated improvement with the continuation of mesalazine therapy alongside comprehensive immunosuppressive treatment, while UC remained stable. This case highlights the importance of considering LN in UC patients presenting with nephrotic syndrome and demonstrates that kidney biopsy is essential for accurate diagnosis and appropriate management."

Clinical • Gastroenterology • Gastrointestinal Disorder • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Lupus • Lupus Nephritis • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Orthopedics • Renal Disease • Systemic Lupus Erythematosus • Ulcerative Colitis

Effect of Cyclosporine- vs. Voclosporin-Based Regimen in a Patient with Class V Lupus Nephritis (KIDNEY WEEK 2025) - "She was started on Plaquenil (hydroxychloroquine) 300 mg daily...She was initially treated with Benlysta (Belimumab) with no response. In Feb 2023, she was started on multiple-targeted therapy with prednisone, mycophenolate mofetil and cyclosporine...Further studies are needed to distinguish if this is an isolated phenomenon or not. Cyclosporine vs Voclosporin in Class V Lupus Nephritis"

Clinical • Alopecia • Dyslipidemia • Fatigue • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Musculoskeletal Pain • Nephrology • Renal Disease