Dataset Information

Risk of Macrophage Activation Syndrome in Patients with Adult-Onset Still's Disease Treated with IL-1 and IL-6 Inhibitors: A Meta-analysis and Single-Center Experience.

ABSTRACT:

Introduction

Patients with adult-onset Still's disease (AOSD) are at risk of developing macrophage activation syndrome (MAS), a life-threatening condition. Some cases of MAS have been reported following the use of biological agents, highlighting the need to identify contributing factors. This study aims to examine the characteristics of MAS in patients with AOSD treated with anakinra (ANA) or tocilizumab (TCZ).

Methods

A systematic search was conducted across four online databases to identify studies reporting the incidence rates of MAS in patients with AOSD treated with ANA or TCZ. Meta-analysis was performed using a random-effects model and the generic inverse variance method to estimate the pooled incidence rates. The difference in incidence rates of MAS between TCZ and ANA was assessed. Additionally, we analyzed laboratory data and clinical features of AOSD cases at our institution, stratifying them into two groups: those who developed MAS after TCZ administration and those who did not.

Results

Of the 455 screened articles, we included five ANA and six TCZ studies. The pooled incidence rates of MAS were 1.50% (95% confidence interval [CI], 0-3.36) for ANA (345 patients) and 14.01% (95% CI 4.51-23.51) for TCZ (94 patients). MAS incidence was significantly higher in the TCZ group (P = 0.01). Among the 17 patients from our institution, the six patients who developed MAS had significantly higher white blood cell and neutrophil counts, as well as elevated levels of lactate dehydrogenase, C-reactive protein, and ferritin before TCZ induction (P < 0.05).

Conclusions

In patients with AOSD, the manifestation of MAS is influenced by multiple causative factors. Consequently, the administration of TCZ should be approached with caution, particularly in patients exhibiting elevated inflammatory markers.

Trial registration

This study was registered with the Clinical Trial Registry of the University Hospital Medical Information Network (Japan) as UMIN000049243.

SUBMITTER: Adachi S

PROVIDER: S-EPMC10654298 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Risk of Macrophage Activation Syndrome in Patients with Adult-Onset Still's Disease Treated with IL-1 and IL-6 Inhibitors: A Meta-analysis and Single-Center Experience.

Adachi Soichiro S Takase-Minegishi Kaoru K Maeda Ayaka A Nagai Hideto H Horita Nobuyuki N Yoshimi Ryusuke R Kirino Yohei Y Nakajima Hideaki H

Rheumatology and therapy 20231004 6

<h4>Introduction</h4>Patients with adult-onset Still's disease (AOSD) are at risk of developing macrophage activation syndrome (MAS), a life-threatening condition. Some cases of MAS have been reported following the use of biological agents, highlighting the need to identify contributing factors. This study aims to examine the characteristics of MAS in patients with AOSD treated with anakinra (ANA) or tocilizumab (TCZ).<h4>Methods</h4>A systematic search was conducted across four online databases ...[more]

PMID: 37794210

Similar Datasets

Project description:BackgroundAdult-onset Still's disease (AOSD) is a systemic autoinflammatory disease characterized by innate immune system activation, with a high risk for macrophage activation syndrome (MAS). MAS development is associated with monocyte/macrophage activation and cytokine storm. Monocytes consist of three different subsets, classical monocytes (CMs, CD14brightCD16 -), intermediate monocytes (IMs, CD14brightCD16 +), and non-classical monocytes (NCMs, CD14dimCD16 +), each has distinct roles in inflammatory regulation. However, the frequencies and regulatory mechanism of monocyte subsets in AOSD patients have not been identified.MethodsWe performed flow cytometry, RNA sequencing, phagocytosis analysis, and enzyme-linked immunosorbent assay to evaluate monocyte subsets, cell functions, and potential biomarkers. The effect of neutrophil extracellular traps (NETs) on monocytes was determined by evaluating mRNA levels of DNA sensors, surface CD16 expression, and inflammasome pathway activation.ResultsHigher proportions of intermediate monocytes (IMs) were identified in active AOSD patients. IMs displayed higher expression of CD80, CD86, HLA-DR, and CD163 than CMs and NCMs. CD163 upregulation was noted on AOSD IMs, accompanied by increased phagocytic activity and elevated cytokine/chemokine production, including IL-1β, IL-6, CCL8, and CXCL10. The frequencies of IMs were correlated with disease activity and higher in AOSD patients with MAS (AOSD-MAS). CCL8 and CXCL10 were highly expressed in RNA sequencing of monocytes from AOSD-MAS patients and plasma CXCL10 level could serve as a potential biomarker for AOSD-MAS. Moreover, DNA-sensing pathway was activated in monocytes from AOSD-MAS patients. Stimulation with NETs derived from AOSD induced DNA sensor expression, the expansion of IMs, and inflammasome pathway activation. These effects can be abrogated by DNase I treatment.ConclusionsOur results demonstrated that the proportions of IMs were elevated in AOSD and associated with MAS. The DNA component in NETs from AOSD plays an important role in the formation of IMs, shedding new light for the therapeutic target.

Dataset Information

Risk of Macrophage Activation Syndrome in Patients with Adult-Onset Still's Disease Treated with IL-1 and IL-6 Inhibitors: A Meta-analysis and Single-Center Experience.

Introduction

Methods

Results

Conclusions

Trial registration

Publications

Risk of Macrophage Activation Syndrome in Patients with Adult-Onset Still's Disease Treated with IL-1 and IL-6 Inhibitors: A Meta-analysis and Single-Center Experience.

Similar Datasets

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