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. 2023 Dec;10(6):1623-1636.
doi: 10.1007/s40744-023-00600-x. Epub 2023 Oct 4.

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

Soichiro Adachi  1 , Kaoru Takase-Minegishi  2 , Ayaka Maeda  1 , Hideto Nagai  1 , Nobuyuki Horita  3 , Ryusuke Yoshimi  1 , Yohei Kirino  1 , Hideaki Nakajima  1
Affiliations

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

Soichiro Adachi et al. Rheumatol Ther. 2023 Dec.

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.

Keywords: Adult-onset Still’s disease; Anakinra; Macrophage activation syndrome; Tocilizumab.

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Figures

Fig. 1
Fig. 1
Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram for the meta-analysis. The studies were selected in accordance with the PRISMA guidelines
Fig. 2
Fig. 2
Forest plot of the incidence rate of MAS. MAS incidence rates were compared between groups treated with ANA and TCZ. CI confidence interval, ANA anakinra, TCZ tocilizumab
Fig. 3
Fig. 3
Scatter dot plots of the laboratory data of patients with and without MAS. The significantly different WBC and neutrophil counts and LDH, CRP, and ferritin levels are shown in the scatterplot dot plot. - lines on the graphs indicate median values. *P < 0.05, **P < 0.01, ***P < 0.001 by the Mann–Whitney U test. AOSD adult-onset Still’s disease, MAS macrophage activation syndrome, ANA anakinra, TCZ tocilizumab, WBC white blood cell, LDH lactate dehydrogenase, CRP C-reactive protein
See this image and copyright information in PMC

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