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 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 Anti-Interleukin-1 Agents in Adult Onset Still's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Cecilia Giampietro ◽  
Bruno Fautrel
Keyword(s):  
Therapeutic Option ◽  
Interleukin 1 ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Still's Disease ◽  
Highly Correlated ◽  
New Generation ◽  
Adult Onset Still's Disease ◽  
Over Time

Interleukin 1β(IL-1β) is emerging as a master mediator of adult onset Still’s disease (AOSD) pathogenesis. This pleiotropic cytokine, whose expression is under the control of the inflammasome pathway, has a wide type of effects. As a key mediator of innate immunity is a potent pyrogen and facilitates neutrophilic proliferation and diapedesis into the inflamed tissues, which are key AOSD manifestations. The study of proinflammatory cytokines profiles in sera and pathological tissues of AOSD patients has shown elevated levels of IL-1β, these levels being highly correlated with disease activity and severity. These experimental evidences and the analogy with other autoinflammatory diseases that share with AOSD clinical and biological characteristics have suggested the blockade of IL-1βas a possible new therapeutic option for the AOSD, especially in conventional therapy resistant cases. Anakinra, the first anti-IL-1 agent put on the market, has demonstrated capable to induce a rapid response sustained over time, especially in systemic forms, where anti-TNFαfailed to control symptoms. While a growing number of evidences supports the utilisation of anakinra in AOSD, a new generation of anti-IL1βantagonists is developing. Canakinumab and rilonacept, thanks to their higher affinity and longer half-life, could improve the management of this invalidating disease.

Beneficial Effect of Interleukin 1 Inhibition with Anakinra in Adult-onset Still’s Disease. An Open, Randomized, Multicenter Study

2012 ◽  
Vol 39 (10) ◽  
pp. 2008-2011 ◽  
Author(s):  
DAN NORDSTRÖM ◽  
ANN KNIGHT ◽  
REIJO LUUKKAINEN ◽  
RONALD van VOLLENHOVEN ◽  
VAPPU RANTALAIHO ◽  
...  
Keyword(s):  
Short Form ◽  
Interleukin 1 ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Open Label ◽  
Link Type ◽  
Still's Disease ◽  
Open Label Extension ◽  
Adult Onset Still's Disease

Objective.To study the efficacy of anakinra versus disease-modifying antirheumatic drugs (DMARD) in refractory adult-onset Still’s disease (AOSD).Methods.In a 24-week study, 22 patients with AOSD taking prednisolone ≥ 10 mg/day received anakinra (n = 12) or DMARD (n = 10). The primary endpoint was achievement of remission.Results.At 8 and 24 weeks, 7/12 and 6/12 receiving anakinra and 5/10 and 2/10 receiving DMARD achieved remission. Anakinra induced greater improvement in physical health measured by Medical Outcomes Study Short-Form 36 (SF-36; p < 0.011). During an open-label extension (OLE) of 28 weeks, 7/14 patients taking anakinra and 2/3 taking DMARD were in remission.Conclusion.Anakinra induced more beneficial responses than DMARD in patients with AOSD and was favored in the OLE phase. (ClinicalTrials.gov Protocol Registration NCT01033656).

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.

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

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Serena Colafrancesco ◽  
◽  
Maria Manara ◽  
Alessandra Bortoluzzi ◽  
Teodora Serban ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Still's Disease ◽  
Consensus Group ◽  
Adult Onset Still's Disease

Following publication of the original article [1], it was brought to our attention that the AOSD Consensus Group was incorrectly tagged and therefore not searchable. The publishers apologize for this error.

Tocilizumab in Adult-onset Still’s Disease: the Israeli Experience

2014 ◽  
Vol 41 (2) ◽  
pp. 244-247 ◽  
Author(s):  
Ori Elkayam ◽  
Nizar Jiries ◽  
Zvi Dranitzki ◽  
Shay Kivity ◽  
Merav Lidar ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Treatment Algorithm ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Disease Modifying Drugs ◽  
Still's Disease ◽  
Randomized Controlled Studies ◽  
Israeli Experience ◽  
Adult Onset Still's Disease

Objective.To describe the Israeli experience of treating adult-onset Still’s disease (AOSD) with tocilizumab (TCZ).Methods.Israeli rheumatologists who treated AOSD with TCZ filled in questionnaires on symptoms, number of tender and swollen joints, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and dosage of prednisone at initial TCZ administration, after 6 months, and at the end of followup.Results.Nine male and 6 female patients, aged 33 ± 12 years, mean disease duration 9 years (range: 1–25) were identified. They had used a mean of 3.6 disease-modifying drugs, including 10 patients with tumor necrosis factor blockers. Intravenous TCZ 8 mg/kg was administered every 4 weeks (12 patients) or every 2 weeks (3 patients). All patients completed at least 6 months of treatment. The mean followup period was 15.7 ± 9 months. At the onset of therapy, despite the use of prednisone (27.6 ± 26.3 mg/d), all patients reported joint pain. Fever was reported in 9 patients, rash in 7, pleuritis in 3, and hepatitis in 2 before TCZ use, with mean ESR and CRP levels of 60 ± 28 mm/h and 11.6 ± 15 mg/dl, respectively. After 6 months of treatment and at the end of followup, the number of tender and swollen joints, the ESR and CRP levels, and the prednisone dosage decreased significantly. Only 2 patients still complained of mild arthralgias, and none reported systemic symptoms at the end of followup.Conclusion.TCZ 8 mg/kg was extremely efficacious in treating adult patients with refractory Still’s disease. Both TCZ and interleukin 1 blockade should be considered in the treatment algorithm of AOSD. Randomized controlled studies are needed to validate these findings.

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