Systematic review, and meta-analysis of steroid-sparing effect, of biologic agents in randomized, placebo-controlled phase 3 trials for systemic lupus erythematosus

Oon, Shereen; Huq, Molla; Godfrey, Timothy; Nikpour, Mandana

doi:10.1016/j.semarthrit.2018.01.001

Cited by 53 publications

(27 citation statements)

References 46 publications

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“…8,9,108 In addition, dual targeting of BAFF and APRIL using TACI-Ig (atacicept) completed phase 2 studies. Of these, the human anti-BAFF antibody belimumab has been the most effective in human clinical trials and is the only agent with FDA approval for the treatment of SLE.…”

Section: Baff-r and Taci Whereas Taci-ig Blocks The Interaction Of Baffmentioning

confidence: 99%

“…Of these, the human anti-BAFF antibody belimumab has been the most effective in human clinical trials and is the only agent with FDA approval for the treatment of SLE. 8,9,108 In addition, dual targeting of BAFF and APRIL using TACI-Ig (atacicept) completed phase 2 studies. 109 Recent studies have shown that belimumab binds to and inhibits the activity of BAFF trimers but not multimers whereas atacicept can bind to both trimers and multimers.…”

Section: Pharmacolog Ic Targ E Ting Of Baff Family C Y Tok Ine S Anmentioning

confidence: 99%

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BAFF inhibition in SLE—Is tolerance restored?

Jackson

Davidson

2019

Immunological Reviews

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The B cell activating factor (BAFF) inhibitor, belimumab, is the first biologic drug approved for the treatment of SLE, and exhibits modest, but durable, efficacy in decreasing disease flares and organ damage. BAFF and its homolog APRIL are TNF‐like cytokines that support the survival and differentiation of B cells at distinct developmental stages. BAFF is a crucial survival factor for transitional and mature B cells that acts as rheostat for the maturation of low‐affinity autoreactive cells. In addition, BAFF augments innate B cell responses via complex interactions with the B cell receptor (BCR) and Toll like receptor (TLR) pathways. In this manner, BAFF impacts autoreactive B cell activation via extrafollicular pathways and fine tunes affinity selection within germinal centers (GC). Finally, BAFF and APRIL support plasma cell survival, with differential impacts on IgM‐ and IgG‐producing populations. Therapeutically, BAFF and combined BAFF/APRIL inhibition delays disease onset in diverse murine lupus strains, although responsiveness to BAFF inhibition is model dependent, in keeping with heterogeneity in clinical responses to belimumab treatment in humans. In this review, we discuss the mechanisms whereby BAFF/APRIL signals promote autoreactive B cell activation, discuss whether altered selection accounts for therapeutic benefits of BAFF inhibition, and address whether new insights into BAFF/APRIL family complexity can be exploited to improve human lupus treatments.

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Section: Baff-r and Taci Whereas Taci-ig Blocks The Interaction Of Baffmentioning

confidence: 99%

Section: Pharmacolog Ic Targ E Ting Of Baff Family C Y Tok Ine S Anmentioning

confidence: 99%

BAFF inhibition in SLE—Is tolerance restored?

Jackson

Davidson

2019

Immunological Reviews

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“…Even with recommended therapeutic strategies, 10–20% patients with LN progress to end-stage renal disease (ESRD) within 5–10 years after diagnosis [ 2 , 3 ]. Several biological agents that regulate autoreactive B and T cells have been developed, but their efficacies have not yet been proven [ 2 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2

Seo

Mun

Park

et al. 2020

IJMS

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Lupus nephritis (LN) is the most frequent phenotype in patients with systemic lupus erythematosus (SLE) and has a high rate of progression to end-stage renal disease, in spite of intensive treatment and maintenance therapies. Recent evidence suggests that protease-activated receptor-2 (PAR2) is a therapeutic target for glomerulonephritis. In this study, we performed a cell-based high-throughput screening and identified a novel potent PAR2 antagonist, punicalagin (PCG, a major polyphenol enriched in pomegranate), and evaluated the effects of PCG on LN. The effect of PCG on PAR2 inhibition was observed in the human podocyte cell line and its effect on LN was evaluated in NZB/W F1 mice. In the human podocyte cell line, PCG potently inhibited PAR2 (IC50 = 1.5 ± 0.03 µM) and significantly reduced the PAR2-mediated activation of ERK1/2 and NF-κB signaling pathway. In addition, PCG significantly decreased PAR2-induced increases in ICAM-1 and VCAM-1 as well as in IL-8, IFN-γ, and TNF-α expression. Notably, the intraperitoneal administration of PCG significantly alleviated kidney injury and splenomegaly and reduced proteinuria and renal ICAM-1 and VCAM-1 expression in NZB/W F1 mice. Our results suggest that PCG has beneficial effects on LN via inhibition of PAR2, and PCG is a potential therapeutic agent for LN.

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“…Current therapeutic approaches cannot meet the clinical demands of patients who have lupus nephritis and are limited by suboptimal efficacy of the treatment and increased risk of infections. Several novel biologic agents for lupus nephritis also show substantial toxicity, and the results of long-term application remain unknown [9][10][11]. Given the complexity, cost and apparent ineffectiveness of the therapeutic armamentarium used in lupus nephritis, complementary and integrative therapies are becoming increasingly attractive [12,13].…”

Section: Introductionmentioning

confidence: 99%

Traditional Chinese Herbal Medicine and Lupus Nephritis

Mu¹,

Jiang²,

Wang³

2018

Health Care Current Reviews

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Available treatments for lupus nephritis, a potentially fatal autoimmune disease, are limited by suboptimal efficacy and increased risk of infections and malignancies; inevitably they do not meet clinical demands. Traditional Chinese herbal medicine has recently been recognized for its potential therapeutic benefits for lupus nephritis. Encouraging evidence from clinical trials and observational studies demonstrate that Chinese herbal medicine may possess benefits for treating patients with lupus nephritis. The significant benefits of these Chinese herbal medicine modalities that have been observed and reported include improving clinical efficacy, reducing level of antibodies and proteinuria, ameliorating renal damage, diminishing the dosage of prednisone use as well as decreasing toxicity, and preventing disease flare-up. This overview aggregates the current body of medical knowledge on the therapeutic benefits of several types of Chinese herbal medicines for lupus nephritis, and these promising herbal medicines may challenge the current treatment paradigms available for lupus nephritis and inform future research and clinical practice.

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Systematic review, and meta-analysis of steroid-sparing effect, of biologic agents in randomized, placebo-controlled phase 3 trials for systemic lupus erythematosus

Cited by 53 publications

References 46 publications

BAFF inhibition in SLE—Is tolerance restored?

BAFF inhibition in SLE—Is tolerance restored?

Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2

Traditional Chinese Herbal Medicine and Lupus Nephritis

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