Progress in Biological Therapies for Adult-Onset Still’s Disease

Galozzi, Paola; Bindoli, Sara; Doria, Andrea; Sfriso, Paolo

doi:10.2147/btt.s290329

Cited by 12 publications

(7 citation statements)

References 101 publications

(99 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In fact, PAP has been widely described in sJIA, but has been observed in only two adults to date [ 43 , 44 ]; however, these findings strengthen the concept that adaptive immunity is involved not only in Still’s disease onset and progression, but also into specific manifestations. The final result of the immunological imbalance is the massive release of pro-inflammatory cytokines and the exuberant production of mediators that may amplify and perpetuate, including IL-1β, IL-6, IL-8, IL-17, TNF-α and IFN-γ; when the production is uncontrolled, the exacerbation of this inflammatory upregulation may provoke the so-called cytokine storm [ 45 ]. The concept of cytokine storm has been extensively mentioned in the last years in the context of coronavirus disease 2019 (COVID-19) infection.…”

Section: Pathophysiology: Main Player and Side Character: The Role Of...mentioning

confidence: 99%

“…NSAIDs can be employed when the diagnosis is still not clear. High doses of indomethacin or ibuprofen may control the inflammatory symptoms in a satisfactory way [ 45 ], however, there are no clinical trials or longitudinal studies exhibiting data on the efficacy of NSAIDs alone. GCs represent an efficient therapeutic approach and remain a cornerstone in AOSD treatment, especially at high doses [ 78 ].…”

Section: Therapeutic Strategies and Cutting-edge Therapies In The Era...mentioning

confidence: 99%

See 1 more Smart Citation

Adult-Onset Still’s Disease (AOSD): Advances in Understanding Pathophysiology, Genetics and Emerging Treatment Options

Bindoli,

Baggio,

Doria

et al. 2024

Drugs

Self Cite

View full text Add to dashboard Cite

Adult-onset Still’s disease (AOSD) is a multisystemic complex disorder clinically characterised by episodes of spiking fever, evanescent rash, polyarthritis or diffuse arthralgias; multiorgan involvement may develop according to the hyper-inflammatory extent. The pathogenesis of AOSD is not completely recognised. The central role of macrophage activation, which results in T helper 1 (Th1) cell cytokine activation, is well established. Pro-inflammatory cytokines such as interleukin (IL)-1, IL-6 and IL-18 play a fundamental role in disease onset and progression. The disease may develop in both children and adults with overlapping clinical features, and although several subsets depending on the clinical manifestations and the cytokines expressed have been identified, the dichotomy between systemic juvenile idiopathic arthritis (sJIA) and AOSD nowadays has been overcome, and the pathology is considered a disease continuum between ages. Various therapeutic approaches have been evaluated thus far, and different compounds are under assessment for AOSD treatment. Historically, glucocorticoids have been employed for treating systemic manifestations of Still’s disease, while conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) demonstrated efficacy in controlling the articular manifestations. Currently, biological (b) DMARDs are widely employed; IL-1 inhibitors such as anakinra and canakinumab have proven to have high efficacy and an excellent safety profile and the anti-IL-6 tocilizumab is approved for sJIA, with several trials and longitudinal studies confirming its efficacy and safety. Moreover, in the light of the ‘window of opportunity’, new evidence showed that the earlier these treatments are initiated, the sooner clinical inactivity can be achieved. Other treatment options are being considered since several molecules involved in the disease pathophysiology can be targeted through various mechanisms. This review will provide a broad overview of AOSD pathophysiology, insights into specific organ manifestations and the currently available treatments with the identification of potential therapeutic targets involved in AOSD pathogenesis will be outlined.

show abstract

Section: Pathophysiology: Main Player and Side Character: The Role Of...mentioning

confidence: 99%

Section: Therapeutic Strategies and Cutting-edge Therapies In The Era...mentioning

confidence: 99%

Adult-Onset Still’s Disease (AOSD): Advances in Understanding Pathophysiology, Genetics and Emerging Treatment Options

Bindoli,

Baggio,

Doria

et al. 2024

Drugs

Self Cite

View full text Add to dashboard Cite

show abstract

“…Möglicherweise können zukünftig Inhibitoren von z. B. IL-18, dem NRLP3-Inflammasom, Interferonen oder Januskinase-Inhibitoren die therapeutischen Optionen erweitern [20]. Eine aktuell in Studien bei sJIA sowie AOSD untersuchte Behandlungsoption stellt beispielsweise der neutralisierende Interferon-γ-Antikörper Emapalumab dar (ClinicalTrials.gov Identifier: NCT05001737).…”

Section: Therapieunclassified

Aktuelles zum adulten Still-Syndrom: Diagnose, Therapiekonzepte und Leitlinie

Vordenbäumen

Feist

2023

Dtsch Med Wochenschr

View full text Add to dashboard Cite

Was ist neu? Epidemiologie Das Still-Syndrom kann sich vom Kindes- bis ins höhere Erwachsenenalter manifestieren – mit jeweils leicht unterschiedlicher klinischer Ausprägung. Pathogenese Das Still-Syndrom ist eine autoinflammatorische Erkrankung unklarer Ätiologie, bei der pathogenetisch das angeborene Immunsystem in Form einer Aktivierung von neutrophilen Granulozyten mit Freisetzung von pro-inflammatorischen Zytokinen IL1, -6, -18, und Typ-1-Interferonen eine zentrale Rolle einnehmen. Diagnose und Differenzialdiagnose In der kürzlich erschienenen DGRh-S2e-Leitlinie zum adulten Still-Syndrom (AOSD) wird empfohlen, die Diagnose anhand der charakteristischen Symptomkonstellation aus u.a. intermittierendem Fieber, Exanthem, Arthralgien/Arthritis nach Ausschluss von Infektionen, Neoplasien und anderen rheumatologischen Erkrankungen zu stellen. Die Erfüllung der Yamaguchi-Klassifikationskriterien kann hierbei die Diagnose unterstützen. Komplikationen Relevante Komplikationen mit Verschlechterung der Prognose sind insbesondere eine Perimyokarditis, eine vielgestaltige Lungenbeteiligung und das Makrophagenaktivierungssyndrom (MAS, auch als sekundäre hämophagozytische Lymphohistiozytose [HLH] bezeichnet). Beim MAS-HLH kommt es zum Zytokinsturm und zu einer Multiorganbeteiligung mit Zytopenien. Therapie Nach klinischer Aktivitätseinschätzung wird eine Therapie mit Glukokortikoiden und Methotrexat oder Ciclosporin, bei höherer Aktivität auch mit dem IL1-Rezeptorantagonisten Anakinra, dem IL1β-Antikörper Canakinumab oder dem IL6-Rezeptorantikörper Tocilizumab empfohlen. Bei hoher Krankheitsaktivität kann gemäß den Leitlinien auch eine primäre Therapie mit Anakinra oder Canakinumab erfolgen. Die Zulassungssituation ist hierbei jeweils zu beachten. Therapeutisch sind in der vital bedrohlichen Situation eines MAS-HLH neben supportiven Intensivmaßnahmen der Einsatz hochdosierter Glukokortikoide, in Kombination mit den genannten Biologika, und ggf. auch Etoposid-haltige Therapieregime in Anlehnung an die Behandlungsempfehlungen anderer HLH-Erkrankungen notwendig.

show abstract

“…Humanized IgG1 monoclonal antibody (anti-IL-18), GSK1070806, is instantly in the development phase for treating a variety of inflammatory conditions, atopic dermatitis (AD) and IBD in phase I, delayed graft function, CD, and Behcet’s disease in phase II (ClinicalTrials.gov Identifier: NCT04975438, NCT01035645, NCT02723786, NCT03681067, NCT03522662) [ 151 ]. In addition to Tadekinig-α and GSK1070806, a long-acting antibody drug targeting IL-18 and APB-R3 is developed for inflammatory autoimmune disease treatment in preclinical stages, and will soon enter phase I clinical trial [ 152 ].…”

Section: Il-18bp In Autoimmune Diseasesmentioning

confidence: 99%

Interleukin-18 Binding Protein in Immune Regulation and Autoimmune Diseases

et al. 2022

View full text Add to dashboard Cite

Natural soluble antagonist and decoy receptor on the surface of the cell membrane are evolving as crucial immune system regulators as these molecules are capable of recognizing, binding, and neutralizing (so-called inhibitors) their targeted ligands. Eventually, these soluble antagonists and decoy receptors terminate signaling by prohibiting ligands from connecting to their receptors on the surface of cell membrane. Interleukin-18 binding protein (IL-18BP) participates in regulating both Th1 and Th2 cytokines. IL-18BP is a soluble neutralizing protein belonging to the immunoglobulin (Ig) superfamily as it harbors a single Ig domain. The Ig domain is essential for its binding to the IL-18 ligand and holds partial homology to the IL-1 receptor 2 (IL-1R2) known as a decoy receptor of IL-1α and IL-1β. IL-18BP was defined as a unique soluble IL-18BP that is distinct from IL-18Rα and IL-18Rβ chain. IL-18BP is encoded by a separated gene, contains 8 exons, and is located at chr.11 q13.4 within the human genome. In this review, we address the difference in the biological activity of IL-18BP isoforms, in the immunity balancing Th1 and Th2 immune response, its critical role in autoimmune diseases, as well as current clinical trials of recombinant IL-18BP (rIL-18BP) or equivalent.

show abstract

Progress in Biological Therapies for Adult-Onset Still’s Disease

Cited by 12 publications

References 101 publications

Adult-Onset Still’s Disease (AOSD): Advances in Understanding Pathophysiology, Genetics and Emerging Treatment Options

Adult-Onset Still’s Disease (AOSD): Advances in Understanding Pathophysiology, Genetics and Emerging Treatment Options

Aktuelles zum adulten Still-Syndrom: Diagnose, Therapiekonzepte und Leitlinie

Interleukin-18 Binding Protein in Immune Regulation and Autoimmune Diseases

Contact Info

Product

Resources

About