tabalumab (LY2127399) / Eli Lilly - LARVOL DELTA

Current status of BAFF targeting immunotherapy in B-cell neoplasm. (PubMed, Int J Clin Oncol) - "Therefore, BAFF-targeted therapies, such as belimumab, atacicept, and tabalumab, are being explored in clinical trials for conditions like chronic lymphocytic leukemia (CLL) and multiple myeloma. Belimumab, an anti-BAFF monoclonal antibody, is being investigated in combination with rituximab/venetoclax for CLL...The review emphasizes the importance of understanding the roles of BAFF and its receptors in the microenvironment of hematologic malignancies. Targeting BAFF and its receptors presents potential therapeutic avenues, and ongoing clinical trials provide valuable insights."

IO biomarker • Journal • Review • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Multiple Myeloma • Oncology

Anti-B-Cell-Activating Factor (BAFF) Therapy: A Novel Addition to Autoimmune Disease Management and Potential for Immunomodulatory Therapy in Warm Autoimmune Hemolytic Anemia. (PubMed, Biomedicines) - "Although rituximab is not specifically approved for the treatment of warm autoimmune hemolytic anemia (WAIHA), the First International Consensus Group recommends considering its use as part of the initial therapy for patients with severe disease and as a second-line therapy for primary WAIHA...This article reviews the role of BAFF in autoimmune disorders and the currently available literature on the use of BAFF-directed therapies in various immunologic disorders, including WAIHA. Collectively, the clinical data thus far shows robust potential for targeting BAFF in WAIHA therapy."

Immunomodulating • Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Fragility of Randomized Clinical Trials of Systemic Lupus Erythematosus and Lupus Nephritis Therapies (ACR Convergence 2023) - "The lowest FI was for the ILLUMINATE-2 trial (score: 2, Tabalumab), and the highest FI was found in the BLISS-52 trial (score: 17, Belimumab). The lowest RFI (non-significant trials) was for the ILLUMINATE-1 trial (score: 4, Tabalumab), and the highest RFI was for the TULIP-1 trial (score: 27, Anifrolumab)...Voclosporin trial (AURORA-1) had an FI score of 15...The lowest FQ scores were found in the ILLUMINATE trials and the highest in the Rituximab trials (LUNAR & EXPLORER) and the early terminated LOTUS trial... The evidence supporting the recent approval of therapies for patients with SLE and LN is derived mostly from fragile RCTs, both among trials that met thresholds for statistical significance and among those that did not. G. Figueroa-Parra:; M. Putman: AbbVie/Abbott, 12, Trial participation, AstraZeneca, 12, Trial participation, Novartis, 2; A. Duarte-Garcia: ."

Clinical • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Validation of a Transcriptomic-Based Machine Learning Model to Establish the Endotype of SLE Patients (ACR Convergence 2023) - P=N/A | "These molecular subsets had significant differences in clinical characteristics, the frequency of subsequent flares, and clinical responsiveness to a lupus biologic, tabalumab... A novel endotyping pipeline based on transcriptional profiles and ML accurately identified patient endotypes in new datasets. Patients in the endotypes with the least immunologic activity did not have proliferative nephritis and also experienced no lupus flares during the subsequent six months. Endotyping SLE patients based on gene expression profiles can provide important prognostic information and provide novel molecular insights in support of personalized management."

Clinical • Machine learning • Asthma • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Pulmonary Disease • Respiratory Diseases

Analysis of transcriptomic features reveals molecular endotypes of SLE with clinical implications. (PubMed, Genome Med) - "Transcriptomic profiling and ML reproducibly separated lupus patients into molecular endotypes with significant differences in clinical features, outcomes, and responsiveness to therapy. Our classification approach using a composite scoring system based on underlying molecular abnormalities has both staging and prognostic relevance."

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

Safety and efficacy of biological agents in the treatment of Systemic Lupus Erythematosus (SLE). (PubMed, BMC Rheumatol) - "Multiple biologic agents are shown in high quality studies to have a significant therapeutic impact on outcomes in SLE."

Journal • Cutaneous Lupus Erythematosus • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • Varicella Zoster • IL12A

Efficacy and Safety of New B Cell-Targeted Biologic Agent for the Treatment of Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis. (PubMed, J Clin Med) - "Belimumab and tabalumab therapies are effective and safe in the treatment of SLE, although tabalumab does not show sufficient statistical power. Advances in understanding the underlying mechanisms of SLE will be directed towards correlating clinical manifestations with specific pathogenic pathways and the development of precision medicine."

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

Advances in natural products and antibody drugs for SLE: new therapeutic ideas. (PubMed, Front Pharmacol) - "This review discusses the current experience including B-cell targeted drugs (belimumab, tabalumab, blisibimod, atacicept, rituximab, ofatumumab, ocrelizumab, obexelimab, and epratuzumab), T-cell targeted drugs (abatacept, dapirolizumab, and inhibitor of syk and CaMKIV), cytokines targeted drugs (anifrolumab and sifalimumab), and natural products (curcumin, oleuropein, punicalagin, sulforaphane, icariin, apigenin, and resveratrol). The aim of this paper is to combine the existing in vitro and in vivo models and clinical research results to summarize the efficacy and mechanism of natural drugs and targeted drugs in SLE for the reference and consideration of researchers."

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

New insights into SLE from machine learning of transcriptomic data (LUPUS-KCR 2023) - "The more abnormal endotypes were significantly more likely to experience a severe flare over the subsequent 52 weeks while on standard-of-care medication and specific endotypes were more likely to be clinical responders to the investigational product tested in one clinical trial analyzed (tabalumab). Transcriptomic profiling and ML reproducibly separated lupus patients into molecular endotypes with significant differences in clinical features, outcomes, and responsiveness to therapy. Our classification approach using a composite scoring system based on underlying molecular abnormalities has both staging and prognostic relevance"

Machine learning • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Scoring Personalized Molecular Portraits Identify Systemic Lupus Erythematosus Subtypes and Predict Individualized Drug Responses, Symptomatology and Disease Progression (ACR Convergence 2022) - "Almost 6100 lupus and 750 healthy samples were used to analyze the association between dysregulation scores, clinical manifestations, prognosis, flare and remission events and drug response to Tabalumab... MyPROSLE (available at https://myprosle.genyo.es) allows molecular characterization of individual Lupus patients and it extracts key molecular information to support more precise therapeutic decisions. Figure 1 shows a summary of the main steps performed on the web tool.Figure 1. Web tool output example."

Clinical • Immunology • Inflammatory Arthritis • Lupus • Nephrology • Systemic Lupus Erythematosus

Identification of Systemic Lupus Erythematosus Endotypes by Analysis of Inflammatory and Immunologic Gene Expression Signatures (ACR Convergence 2022) - "The six endotypes were finally characterized by associated patient metadata and response to the anti-BAFF therapy, tabalumab. Gene expression profiles of adult SLE patients by 32 immune and inflammatory features revealed six distinct endotypes (Figure 1)...HCQ = hydroxychloroquine. MMF = mycophenolate mofetil. AZA = azathioprine. MTX = methotrexate... Transcriptomic profiling using GSVA and machine learning identified molecular endotypes of lupus patients with significant differences in clinical outcomes and responsiveness to therapy.Figure 1. Endotypes in Adult SLEIterative k-means clustering of GSVA scores of the 32 features in 1620 adult lupus patients from GSE88884 yielded six clusters using baseline gene expression. Shorthand labels indicate patient clusters and color names were randomly generated using the ‘grDevices’ color palette in R. Native American ancestry refers to Hispanic patients.Figure 2."

Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Scoring Personalized Molecular Portraits Identify Systemic Lupus Erythematosus Subtypes and Predict Individualized Drug Responses, Symptomatology and Disease Progression (ACR Convergence 2022) - "Almost 6100 lupus and 750 healthy samples were used to analyze the association between dysregulation scores, clinical manifestations, prognosis, flare and remission events and drug response to Tabalumab... MyPROSLE (available at https://myprosle.genyo.es) allows molecular characterization of individual Lupus patients and it extracts key molecular information to support more precise therapeutic decisions. Figure 1 shows a summary of the main steps performed on the web tool.Figure 1. Web tool output example."

Clinical • Immunology • Inflammatory Arthritis • Lupus • Nephrology • Systemic Lupus Erythematosus

Distinct binding mode of BAFF antagonist antibodies belimumab and tabalumab, analyzed by computer simulation. (PubMed, J Mol Model) - "More importantly, belimumab could bind to L83 of BAFF and produce steric hindrance with the adjacent BAFF trimers, while tabalumab could not. Therefore, our results indicated that belimumab has a better clinical outcome compared with tabalumab mainly because belimumab could bind to L83 of BAFF and interfere the formation of a BAFF 60-mer, besides mediating inhibition of the interaction of BAFF with its receptors."

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

External Validation of the Lupus Multivariable Outcome Score for Systemic Lupus Erythematosus Trials. (PubMed, ACR Open Rheumatol) - "LuMOS 2.0 detected significantly greater treatment effects compared with the SRI-5 in the Illuminate trials. Additional validation of LuMOS 2.0 in trials of non-B cell-directed therapies will be necessary to document its universality as an outcome measure."

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

Scoring personalized molecular portraits identify Systemic Lupus Erythematosus subtypes and predict individualized drug responses, symptomatology and disease progression. (PubMed, Brief Bioinform) - "MyPROSLE (https://myprosle.genyo.es) allows molecular characterization of individual Lupus patients and it extracts key molecular information to support more precise therapeutic decisions."

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

What Have Failed, Interrupted, and Withdrawn Antibody Therapies in Multiple Sclerosis Taught Us? (PubMed, Neurotherapeutics) - "mAbs that have been proven to be safe in other autoimmune conditions, will not have the same safety profile in MS due to immunopathogenetic differences in these diseases (e.g., daclizumab)...Memory B cells are central players in MS immunopathogenesis (e.g., tabalumab)...The success of trials on remyelination-promoting therapies mainly depends on the sufficient high dose of mAb, the optimal readout for 'proof of concept', time of treatment initiation, and appropriate selection of patients. Failed strategies are highly important to better understand assumed immunopathophysiological mechanisms and optimizing future trial designs."

Journal • Review • CNS Disorders • Immunology • Multiple Sclerosis

Advances of using antibody against B cell activating factor for treatment of autoimmune diseases (PubMed, Sheng Wu Gong Cheng Xue Bao) - "In connection to the treatment of the above three diseases, this review discusses the clinical trials and application status of three BAFF-targeting antibody drugs, including Belimumab, Tabalumab and Atacicept. Finally, this review proposes new strategies that targeting the BAFF pathway to provide a new treatment for autoimmune diseases."

Journal • Immunology • Inflammatory Arthritis • Lupus • Oncology • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus • TNFA

[VIRTUAL] Effects of B Cell Activating Factors/B Lymphocyte Stimulator Inhibitors Added to Standard of Care on Infection in Patients with Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (ACR-CONVERGENCE 2021) - " A systematic literature review was performed in PubMed, Embase, Cochrane Library databases from inception to Feb 2021 to identify randomized controlled trials (RCTs) of BAFFi/BLySi, including belimumab, tabalumab, blisibimod and atacicept. Adding BAFFi/BLySi to SoC in patients with SLE was not associated with increased risk of infection, serious infection, nor fatal infection."

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

[VIRTUAL] Efficacy of Anifrolumab in Patients with SLE Previously Treated with Biologics: Post Hoc Analysis of Data from 2 Phase 3 Trials (ACR-CONVERGENCE 2021) - P3 | "Efficacy measures included BILAG–based Combined Lupus Assessment (BICLA) response at Week (W) 52; SLE Responder Index of ≥4 (SRI[4]) response at W52; sustained oral glucocorticoid (GC) taper (≤7.5 mg/day prednisone equivalent, W40−52, if ≥10 mg/day at baseline); and annualized flare rate through W52...Most previous biologic use was with belimumab (n=70), epratuzumab (n=49), tabalumab (n=18), or rituximab (n=14)... Regardless of whether patients with SLE had previously received biologics, anifrolumab 300 mg provided clinically meaningful benefit over placebo across efficacy endpoints and was generally well tolerated. 1. Furie RA."

Clinical • P3 data • Retrospective data • Herpes Zoster • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Varicella Zoster

[VIRTUAL] Validation of a Novel Lupus Multivariable Outcome Score as an Outcome Measure for Systemtic Lupus Erythematosus Trials (ACR-CONVERGENCE 2021) - " Validation was carried out in the Illuminate trials used to evaluate tabalumab (TB) in SLE...To adapt LuMOS for use with laboratory results assessed on different platforms than used in the trials of belimumab employed to generate the original LuMOS outcome score [1], we calculated a standardized score using z-score transformation... LuMOS improves the ability to detect statistically significant treatment effects. Further validation in SLE trials of non-B cell directed treatments is necessary to document utility as an outcome measure independent of drug mechanism. [1] Abrahamowicz et al."

Immunology • Inflammatory Arthritis • Lupus • Rheumatology • Systemic Lupus Erythematosus

[VIRTUAL] Association Between Anti-RNP Antibodies and Interferon Gene Expression but Not Complement Consumption in SLE (ACR-CONVERGENCE 2021) - "Extensive laboratory measurements from 2 clinical trials of tabalumab in SLE (ILLUMINATE 1&2) allowed analysis of the relationships between autoantibody levels, ISG expression, and complement (C) C3 and C4 levels... Taken together, these data indicate that anti-RNP antibodies are associated with ISG expression more strongly than anti-dsDNA antibodies, but are not related to the depression of C3 or C4. Furthermore, ISG expression is not required for autoantibody production, but autoantibodies are likely directionally related to the ISG signature. Figure 2."

CNS Disorders • Depression • Inflammatory Arthritis • Psychiatry • IFNA1 • IFNB1 • IFNG

[VIRTUAL] PERSONALIZED MOLECULAR PORTRAITS OF SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS AS KEY FOR PROGNOSIS AND THERAPEUTIC DECISIONS (LUPUS 2021) - "Drug response to hydroxychloroquine and mycophenolate was analyzed comparing molecular portraits. A third dataset of 1760 patients was used to measure the response to Tabalumab. The system allows to quantify the dysregulation of 30 gene-modules in individual patients with respect to healthy distributions. MyPROSLE allows to extract information from the patients useful for medical practice and may be a support for more precise therapeutic decisions in the future."

Clinical • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

[VIRTUAL] VALIDATION OF A NOVEL LUPUS MULTIVARIABLE OUTCOME SCORE AS AN OUTCOME MEASURE FOR SLE TRIALS (LUPUS 2021) - "Aims: External validation of LuMOS in independent trials that evaluated tabalumab rather than belimumab. : We calculated LuMOS scores at week 52 for all participants in the Illuminate trials of tabalumab (TB). : LuMOS improves ability to detect statistically significant treatment effects. Further validation in SLE trials of non-B cell directed treatments is necessary to document utility as an outcome measure independent of drug mechanism."

Immunology • Inflammatory Arthritis • Lupus • Rheumatology

[VIRTUAL] Efficacy of Biological Agents for the Management of Systemic Lupus Erythematosus: A Systematic Review and Network Meta-Analysis (CRA-AHPA 2021) - "These 20 RCTs investigated the following biologics: belimumab, anifrolumab, ustekinumab, atacicept, baricitinib, blisibimod, epratuzumab, IL-2, lupuzor, PF-04236921, rontalizumab, sifalimumab, and tabalumab... The NMA identified that belimumab, anifrolumab and ustekinumab demonstrated greater response in comparison to placebo, when measured using SRI. This systematic review identified that there was heterogeneity in the outcome measures and endpoints used. In the future, the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be applied to rate the quality of the evidence, and to gain insight into methodological pitfalls that could have negatively altered the results of RCTs."

Retrospective data • Review • Complement-mediated Rare Disorders • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus • IL2

Emerging B-Cell Therapies in Systemic Lupus Erythematosus. (PubMed, Ther Clin Risk Manag) - "This review discusses the current experience with B-cell-targeted therapies, including those targeting B-cell-surface antigens (rituximab, ocrelizumab, ofatumumab, obinutuzumab, obexelimab, epratuzumab, daratumumab), B-cell survival factors (belimumab, tabalumab, atacicept, blisibimod), or B-cell intracellular functions (ibrutinib, fenebrutinib, proteasome inhibitors), for the management of SLE. It focuses on ongoing clinical trials and real-world post-marketing use, where available, including their safety profiles, and concludes with our recommendations for B-cell-centric approaches to the management of SLE."

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