scholarly journals Update on the therapy of adult-onset Still’s disease with a focus on IL-1-inhibition: a systematic review

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110595
Author(s):  
Claudia Kedor ◽  
Stylianos Tomaras ◽  
Daniel Baeumer ◽  
Eugen Feist
Keyword(s):  
Systematic Review ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Case Series ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
The Past ◽  
Still's Disease ◽  
Randomized Controlled Studies ◽  
Adult Onset Still's Disease

Introduction: The past decade has seen increasingly rapid advances in understanding the pathogenic nature of adult-onset Still’s disease (AOSD) and its shared symptoms with the systemic juvenile idiopathic arthritis (sJIA). Interleukin-1 (IL-1) blocking agents are key elements in the treatment. In this updated systematic review, we focus on studies on efficacy and safety of IL-1 blockers published in the past 5 years and review on latest available therapies. Methods: We conducted searches using Medline, Biosis, Embase, and Cochrane databases between 2016 and 2021 using the terms AOSD, IL1, IL-18, canakinumab, anakinra, tadekinig, and rilonacept and if applicable their trade names. Duplicates, case reports, and manuscripts with incomplete data were excluded. Results: Of the 1013 screened publications, 17 were eligible after careful selection. We only found two published randomized controlled studies in the past 5 years. Review manuscripts of rare diseases, like our work, usually rely on retrospective studies and case series. Anakinra and canakinumab can be successfully used as first- or further-line treatment in patients with AOSD refractory to steroids. A homogeneous outcome is not established yet. Thus, a combination of clinical and laboratory tests can support the experienced clinician in the decision-making process. Conclusion: The approval of IL-1 inhibitors for AOSD brought us into a new era in the treatment of AOSD. The overall efficacy-safety profile of the IL-1 inhibitors is favorable reflecting a targeted approach as standard of care. We can expect that the successful treatment of AOSD with IL-1 inhibition will facilitate further clinical and basic research with impact on other auto-inflammatory and hyper-inflammatory conditions.

scholarly journals The Role of Interleukin 18/Interleukin 18-Binding Protein in Adult-Onset Still’s Disease and Systemic Juvenile Idiopathic Arthritis

2022 ◽  
Vol 11 (2) ◽  
pp. 430
Author(s):  
Charlotte Girard-Guyonvarc’h ◽  
Mathilde Harel ◽  
Cem Gabay
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Binding Protein ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Free Form ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Interleukin 18 ◽  
Still's Disease ◽  
Adult Onset Still's Disease

Interleukin 18 (IL-18) is a pro-inflammatory cytokine of the IL-1 family, whose activity is tightly controlled at the level of production, as well as signalization. Notably, it is buffered by its natural inhibitor, IL-18 binding protein (IL-18BP), which is massively present in circulation in normal and in most pathological conditions, thus preventing harmful pro-inflammatory systemic effects of IL-18. IL-18 has long been considered to be involved in the pathophysiology of various inflammatory diseases. However, a first clinical trial using recombinant IL-18BP for the treatment of rheumatoid arthritis and psoriasis gave disappointing results. Direct measurements of unbound, bioactive, free form of circulating IL-18 demonstrated that IL-18 was more specifically involved in adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA) but also in their most severe complication, macrophage activation syndrome (MAS). More importantly, administration of recombinant IL-18BP to patients with AOSD, and sJIA with MAS, showed promising results. This review summarizes available data regarding IL-18 and IL-18BP in AOSD and sJIA in mouse models and humans and shows the importance of IL-18/IL-18BP imbalance in these conditions, leading to the conclusion that IL-18, particularly free IL-18, may be a useful biomarker in these diseases and an interesting therapeutic target.

scholarly journals Management of adult-onset Still’s disease with interleukin-1 inhibitors: evidence- and consensus-based statements by a panel of Italian experts

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Serena Colafrancesco ◽  
◽  
Maria Manara ◽  
Alessandra Bortoluzzi ◽  
Teodora Serban ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Delphi Process ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Biologic Treatment ◽  
Still's Disease ◽  
Late Treatment ◽  
Adult Onset Still's Disease

Abstract Background Adult-onset Still’s disease (AOSD) is a rare inflammatory condition characterized by fever, rash, and arthritis. Because of its rarity, clinical trials are inherently small and often uncontrolled. Our objective was to develop recommendations for the use of interleukin (IL)-1 inhibitors in the management of patients with AOSD, based on the best evidence and expert opinion. Methods A panel of 10 experts (9 rheumatologists and 1 pediatrician) was established. The first step was dedicated to a comprehensive literature review and development of statements. Two separate literature searches were performed on the MEDLINE (Pubmed), EMBASE, and BIOSIS databases through April 2018 to identify (1) differences and similarities between AOSD and pediatric Still’s disease (systemic juvenile idiopathic arthritis [SJIA]) and (2) the efficacy and safety of IL-1 inhibitors in AOSD treatment. In the second step, the statements were submitted in a Delphi process to a panel of 67 rheumatologists. Consensus threshold was set at 66%: positive, > 66% of voters selected scores 3 to 5; negative, > 66% of voters selected scores 1 or 2. In the third step, the voting results were analyzed, and the statements were finalized. Results Eleven statements were developed. Forty-six of 67 rheumatologists (72%) participated in the Delphi process. A positive consensus was reached after the first round of voting and was full (> 95%) on the majority of statements. A large consensus was achieved in considering AOSD and SJIA as the same disease. The use of anti-IL-1 therapies in refractory patients was considered quite safe and effective both as the first and as a subsequent line of biologic treatment, especially in systemic patients. Because of the lack of head-to-head comparisons, a different profile of efficacy among IL-1 inhibitors could not be established. There was a large consensus that failure of the first IL-1 inhibitor does not preclude response to another one. The lack of studies comparing early versus late treatment did not allow to draw conclusions; however, data from SJIA suggest a better response in early treatment. Conclusions The Delphi method was used to develop recommendations that we hope will help clinicians in the management of patients with AOSD refractory to conventional therapies.

scholarly journals Adult-Onset Still’s Disease Associated with Thyroid Dysfunction: Case Report and Review of the Literature

2014 ◽  
Vol 8 (1) ◽  
pp. 9-12 ◽  
Author(s):  
Yingchun Hu ◽  
Han Wang ◽  
Juelin Deng
Keyword(s):  
Autoimmune Disease ◽  
Lupus Erythematosus ◽  
Adult Onset Still’S Disease ◽  
Systemic Autoimmune Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Autoimmune Thyroid ◽  
The Past ◽  
Still's Disease ◽  
Adult Onset Still's Disease

To our knowledge, the possible unveiled interaction between adult-onset Still’s disease (AOSD) with autoimmune thyroid disease (AITD) has never been reported although it is well established that systemic autoimmune disease may usually occur in relation to AITD. As increasingly clear links of AITD with other autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren’s syndrome (pSS) have been reported, and the incidence of AOSD concurrent AITD draws our attention rapidly. In this study, we searched relevant literatures published in the past 30 years to explore that condition.

scholarly journals An Update on the Pathogenic Role of Neutrophils in Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still’s Disease

2021 ◽  
Vol 22 (23) ◽  
pp. 13038
Author(s):  
Ji-Won Kim ◽  
Mi-Hyun Ahn ◽  
Ju-Yang Jung ◽  
Chang-Hee Suh ◽  
Hyoun-Ah Kim
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Immune Defense ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Still's Disease ◽  
Wide Range ◽  
Adult Onset Still's Disease

Neutrophils are innate immune phagocytes that play a key role in immune defense against invading pathogens. The main offensive mechanisms of neutrophils are the phagocytosis of pathogens, release of granules, and production of cytokines. The formation of neutrophil extracellular traps (NETs) has been described as a novel defense mechanism in the literature. NETs are a network of fibers assembled from chromatin deoxyribonucleic acid, histones, and neutrophil granule proteins that have the ability to kill pathogens, while they can also cause toxic effects in hosts. Activated neutrophils with NET formation stimulate autoimmune responses related to a wide range of inflammatory autoimmune diseases by exposing autoantigens in susceptible individuals. The association between increased NET formation and autoimmunity was first reported in antineutrophil cytoplasmic antibody-related vasculitis, and the role of NETs in various diseases, including systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, has since been elucidated in research. Herein, we discuss the mechanistic role of neutrophils, including NETs, in the pathogenesis of systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still’s disease (AOSD), and provide their clinical values as biomarkers for monitoring and prognosis.

Serum S100A8/A9, But Not Follistatin-like Protein 1 and Interleukin 18, May Be a Useful Biomarker of Disease Activity in Adult-onset Still’s Disease

2012 ◽  
Vol 39 (7) ◽  
pp. 1399-1406 ◽  
Author(s):  
HYOUN-AH KIM ◽  
JEONG-MI AN ◽  
JIN-YOUNG NAM ◽  
JA-YOUNG JEON ◽  
CHANG-HEE SUH
Keyword(s):  
Disease Activity ◽  
Systemic Disease ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Disease Score ◽  
Still’S Disease ◽  
Interleukin 18 ◽  
Still's Disease ◽  
Adult Onset Still's Disease

Objective.S100A8/A9, follistatin-like protein 1, and interleukin 18 (IL-18) have been suggested as biomarkers of disease activity in patients with systemic juvenile idiopathic arthritis or adult-onset Still’s disease (AOSD). We investigated the clinical significance of these factors in AOSD.Methods.Blood samples were collected from 36 patients with AOSD, 40 patients with rheumatoid arthritis (RA), and 33 healthy controls. Of the patients with AOSD, followup samples were collected from 16 patients after resolution of disease activity.Results.Serum levels of S100A8/A9 (11.77 ± 8.84 μg/ml) in AOSD patients were higher than those in RA patients (3.53 ± 3.43 μg/ml; p < 0.001) and controls (2.49 ± 1.83 μg/ml; p < 0.001). Follistatin-like protein 1 levels in AOSD were not different from those in RA and controls. IL-18 levels in AOSD (7560.3 ± 7577.6 pg/ml) were higher than those in RA (217.7 ± 292.1 pg/ml; p < 0.001) and controls (139.2 ± 86.2 pg/ml; p < 0.001). The sensitivity and specificity of IL-18 for diagnosing AOSD was highest with a cutoff value of 366.1 pg/ml. Serum S100A8/A9 correlated with leukocyte count, erythrocyte sedimentation rate, C-reactive protein, ferritin, and systemic disease score; however, IL-18 correlated only with ferritin and systemic disease score. S100A8/A9 was decreased after disease activity was resolved in followup of AOSD patients (9.96 ± 7.35 μg/ml in active AOSD vs 3.6 ± 4.77 μg/ml in resolved cases; p = 0.001). The change of S100A8/A9 was well correlated with that of systemic disease score.Conclusion.The data suggest that serum S100A8/A9 may be a useful biomarker for evaluating disease activity in patients with AOSD.

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