Efficacy and safety of subcutaneous tabalumab, a monoclonal antibody to B-cell activating factor, in patients with systemic lupus erythematosus: results from ILLUMINATE-2, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study

Merrill, Joan T.; Vollenhoven, Ronald F. van; Buyon, Jill P.; Furie, Richard; Stohl, William; Morgan-Cox, M; Dickson, Christina; Anderson, Pamela W.; Lee, C; P-Y., Berclaz; Dörner, Thomas

doi:10.1136/annrheumdis-2015-207654

Cited by 197 publications

(149 citation statements)

References 22 publications

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“…Clinical testing of tabalumab in SLE has been limited to two separate phase-III studies. The clinical endpoint was met in one of these trials [69] but not in the other [70]. The safety profile was favorable in each trial.…”

Section: ) Tabalumabmentioning

confidence: 72%

“…Of the eight late-stage clinical trials of BAFF antagonists in SLE reported to date in complete manuscript form, only four met their respective primary endpoints: each of the three phase-III trials of belimumab [57,58,64], and one of the two phase-III trials of tabalumab [69]. The phase-II belimumab trial, the phase-IIb blisibimod trial, the phase-II/III atacicept trial, and one of the two phase-III tabalumab trials all failed [67,70,72,73].…”

Section: Can the Limited Clinical Efficacy Of Baff Antagonists Be Ovementioning

confidence: 99%

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The Future of B-cell Activating Factor Antagonists in the Treatment of Systemic Lupus Erythematosus

Stohl

2017

J Rheum Dis

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s personal library were searched. BAFF-antagonist therapy in SLE has a checkered past, with four late-stage clinical trials meeting their primary endpoints and four failing to do so. Additional late-stage clinical trials are enrolling subjects to address some of the remaining unresolved questions, and novel approaches are proposed to improve results. The BAFF-centric pathway is a proven therapeutic target in SLE. As the only pathway in the past 50+ years to have yielded an United States Food and Drug Administration-approved drug for SLE, it occupies a unique place in the armamentarium of the practicing rheumatologist. The challenges facing clinicians and investigators are how to better tweak the BAFF-centric pathway and improve on the successes realized. (J Rheum Dis 2017;24:65-73)

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Section: ) Tabalumabmentioning

confidence: 72%

Section: Can the Limited Clinical Efficacy Of Baff Antagonists Be Ovementioning

confidence: 99%

The Future of B-cell Activating Factor Antagonists in the Treatment of Systemic Lupus Erythematosus

Stohl

2017

J Rheum Dis

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“…An SRI-5 response at week 52 was achieved in the 120-mg every 2 weeks regimen (38.4 vs. 27.7%, placebo), but not with the less-frequent 120 mg every 4 weeks regimen (34.8%) [142]. Anti-dsDNA levels decreased in both tabalumab groups as early as week 4 and continued to decrease, remaining well below baseline levels through week 52.…”

Section: Tabalumabmentioning

confidence: 88%

“…In a study of tabalumab in SLE, a total of 2288 SLE patients were randomized (n = 1164 in ILLUMINATE-1 and n = 1124 in ILLUMINATE-2) to receive tabalumab or placebo [141,142].…”

Section: Tabalumabmentioning

confidence: 99%

The Roles of the TNF-Family Member B-Cell Activation Factor Belonging to the TNF-Family (BAFF) in Autoimmunity

Hirayama¹,

Nagai²

2017

Immunopathogenesis and Immune-Based Therapy for Selected Autoimmune Disorders

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The tumor necrosis factor superfamily (TNFSF) member and cytokine known as B-cell activation factor belonging to the TNF-family (BAFF) has been identified as one of the key factors in the selection and survival of B cells. Overexpression of BAFF in mice leads to autoimmunity, whereas BAFF-deficient mice lack mature B cells. Although under normal concentrations of BAFF, non-self-reactive B cells survived and autoreactive B cells were deleted, a higher concentration of BAFF contributed to the survival of autoreactive B cells and elevated autoantibody production. Lupus-prone mice have increased serum levels of BAFF during the onset and progression of disease. The serum BAFF levels are elevated in patients with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and ANCA-associated vasculitis, and showed positive correlations with autoantibodies.

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“…But the primary endpoint of SLE responder index 5 has been only met in ILLUMINATE-2 at the dose of 120 mg Q2w, but not met at the dose of 120 mg Q4w and in ILLUMINATE-1 study. These trials suggest that the dosing strategy and the demographic characteristics have important influence on the therapeutic effects, and regime for different patients should be optimized [203,204].…”

Section: Blisibimod/tabalumabmentioning

confidence: 99%

B cells biology in systemic lupus erythematosus—from bench to bedside

Zhang

2015

Sci. China Life Sci.

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Systemic lupus erythematosus (SLE) is a debilitating autoimmune disease that can involve multi-organs. B cells play a central role in the immunopathogenesis via antibody-dependent and antibody-independent ways. Excessive autoantibodies production, hyperresponsiveness and prolonged survival of autoreactive B cells are characteristics of SLE. In this article, mechanisms of self-tolerance loss of B cells and promising B cell-targeting therapies in lupus are reviewed and discussed. Systemic lupus erythematosus (SLE), the paradigm of autoimmune disease with the underlying mechanisms involving multiple immunological abnormalities, is a severely debilitating disease with multi-organ involvement and diverse autoantibodies spectrum [1]. Among the multiple elements in the pathogenesis, B cells play a central role in SLE through antibody dependent and independent manners [2]. Presence of pathogenic autoantibodies is not only the hallmark of SLE and the clue for diagnosis, but also associated with characteristic pathological injury and specific clinical manifestations [3][4][5]. In addition, the pathogenic role of B cells is also attributed to its antibody independent functions, including but not limited to antigen presentation, T cell crosstalk, dendritic cells (DCs) recruitment, pro-inflammatory cytokine secretion. Why and how auto-reactive B cells in lupus lose self-tolerance, escape from central and peripheral checkpoints, become over-activated and spontaneously produce autoantibodies, are always the focus of clinical and basic research. Therefore, it is important to summarize our current knowledge about the underlying mechanisms of self-tolerance breakdown and pathogenic functioning pathways of B cells in SLE. So we review here about B cell biology in SLE, including its differentiation and selection, functioning and signaling, surviving and apoptosis, and the resulting potential therapeutic targets both in mice and human lupus.

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Efficacy and safety of subcutaneous tabalumab, a monoclonal antibody to B-cell activating factor, in patients with systemic lupus erythematosus: results from ILLUMINATE-2, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study

Cited by 197 publications

References 22 publications

The Future of B-cell Activating Factor Antagonists in the Treatment of Systemic Lupus Erythematosus

The Future of B-cell Activating Factor Antagonists in the Treatment of Systemic Lupus Erythematosus

The Roles of the TNF-Family Member B-Cell Activation Factor Belonging to the TNF-Family (BAFF) in Autoimmunity

B cells biology in systemic lupus erythematosus—from bench to bedside

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