Efficacy and safety of Janus kinase inhibitors in systemic and cutaneous lupus erythematosus: A systematic review and meta-analysis

Ma, Leyao; Peng, Liying; Zhao, Jiuliang; Bai, Wei; Jiang, Nan; Zhang, Shangzhu; Wu, Chanyuan; Wang, Li; Xu, Dong; Leng, Xiaomei; Wang, Qian; Zhang, Wen; Zhao, Yan; Tian, Xinping; Li, Mengtao; Zeng, Xiaofeng

doi:10.1016/j.autrev.2023.103440

Cited by 6 publications

(3 citation statements)

References 51 publications

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“…Tofacitinib, a JAK1/JAK3 inhibitor, is currently in phase II studies for SLE treatment and is worthy of consideration in this regard 42 . Hence, JAK-STAT inhibitors have been shown initial promising results for SLE treatment although with limited serological activity 43 . However, two recent phase 3 clinical trials using a selective JAK1/2 inhibitor have been discontinued after disappointing results 44 , 45 .…”

Section: Discussionmentioning

confidence: 99%

IRAK4 is an immunological checkpoint in neuropsychiatric systemic lupus erythematosus

Ménoret,

Agliano,

Karginov

et al. 2024

Sci Rep

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The search for dementia treatments, including treatments for neuropsychiatric lupus (NPSLE), has not yet uncovered useful therapeutic targets that mitigate underlying inflammation. Currently, NPSLE’s limited treatment options are often accompanied by severe toxicity. Blocking toll-like receptor (TLR) and IL-1 receptor signal transduction by inhibiting interleukin-1 receptor-associated kinase 4 (IRAK4) offers a new pathway for intervention. Using a pre-clinical NPSLE model, we compare lupus-like B6.MRL-Faslpr (MRL) mice with B6.MRL-Faslpr-IRAK4 kinase-dead (MRL-IRAK4-KD) mice, which are were less prone to ‘general’ lupus-like symptoms. We demonstrate that lupus-prone mice with a mutation in the kinase domain of IRAK4 no longer display typical lupus hallmarks such as splenomegaly, inflammation, production of hormones, and anti-double-stranded (ds)DNA antibody. water maze behavioral testing, which measures contextual associative learning, revealed that mice without functional IRAK4 displayed a recovery in memory acquisition deficits. RNA-seq approach revealed that cytokine and hormone signaling converge on the JAK/STAT pathways in the mouse hippocampus. Ultimately, the targets identified in this work may result in broad clinical value that can fill the significant scientific and therapeutic gaps precluding development of cures for dementia.

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Section: Discussionmentioning

confidence: 99%

IRAK4 is an immunological checkpoint in neuropsychiatric systemic lupus erythematosus

Ménoret,

Agliano,

Karginov

et al. 2024

Sci Rep

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“…При некоторых, достаточно редко встречающихся заболеваниях, даже проведение РКИ не всегда возможно. В этих случаях метаанализы, объединяющие результаты небольших исследований, являются практически единственным способом получить данные об истинном эффекте вмешательства [17], причем далеко не всегда эти исследования будут рандомизированными [18]. Правда, в этом случае обязательно возникнет вопрос об однородности методов проведения и оценки результата в этих небольших исследованиях.…”

Section: метаанализы в кардиологииunclassified

Is meta-analysis the "top of the evidence pyramid" in cardiology?

Martsevich

2024

Cardiovasc Ther Prev

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The author comments on the significance and place of meta-analyses in modern evidence-based medicine, primarily in cardiology. The history of meta-analyses is briefly described. The main limitations of meta-analyses are reviewed. Examples are given where meta-analyses on the same problem had directly opposite results. The importance of meta-analyses in identifying side effects of drugs is discussed. The possibility of manipulating the results of meta-analyses is demonstrated. The significance of meta-analyses is currently being assessed through the example of the coronavirus pandemic, when different meta-analyses assessed the effectiveness and safety of the same drugs differently.The author concludes that meta-analyses should be excluded from level I evidence and given a more modest role in the hierarchy of evidence.

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“…An important role of type I IFN in disease progression suggests that medications designed to inhibit IFN-α/β receptors such as anifrolumab ( 106 ), may offer significant benefits to those suffering from mendelian SLE-like interferonopathies. Additional therapeutic options to decrease type I IFN signaling and formation of pathogenic ABCs cells include JAK inhibitors such as baricitinib and ruxolitinib ( 107 , 108 ). Additionally, reverse transcriptase inhibitors, originally developed for HIV patients, have the potential to target endogenous retroviruses propose to be important SLE triggers ( 109 ) and reduce the IFN signature ( 110 ).…”

Section: Introductionmentioning

confidence: 99%

Monogenic lupus: insights into disease pathogenesis and therapeutic opportunities

Qin,

Ma,

Vinuesa

2024

Current Opinion in Rheumatology

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Purpose of review This review aims to provide an overview of the genes and molecular pathways involved in monogenic lupus, the implications for genome diagnosis, and the potential therapies targeting these molecular mechanisms. Recent findings To date, more than 30 genes have been identified as contributors to monogenic lupus. These genes are primarily related to complement deficiency, activation of the type I interferon (IFN) pathway, disruption of B-cell and T-cell tolerance and metabolic pathways, which reveal the multifaceted nature of systemic lupus erythematosus (SLE) pathogenesis. Summary In-depth study of the causes of monogenic lupus can provide valuable insights into of pathogenic mechanisms of SLE, facilitate the identification of effective biomarkers, and aid in developing therapeutic strategies.

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Efficacy and safety of Janus kinase inhibitors in systemic and cutaneous lupus erythematosus: A systematic review and meta-analysis

Cited by 6 publications

References 51 publications

IRAK4 is an immunological checkpoint in neuropsychiatric systemic lupus erythematosus

IRAK4 is an immunological checkpoint in neuropsychiatric systemic lupus erythematosus

Is meta-analysis the "top of the evidence pyramid" in cardiology?

Monogenic lupus: insights into disease pathogenesis and therapeutic opportunities

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