Interleukin-1 Blockade in Polygenic Autoinflammatory Disorders: Where Are We now?
| Autor: | Hana Malcova, Tomas Milota, Zuzana Strizova, Dita Cebecauerova, Ilja Striz, Anna Sediva, Rudolf Horvath |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Gevokizumab systemic juvenile idiopathic arthritis Arthritis Disease Review canakinumab idiopathic recurrent pericarditis 03 medical and health sciences 0302 clinical medicine rilonacept medicine Pharmacology (medical) 030203 arthritis & rheumatology Pharmacology Anakinra business.industry IL-1 lcsh:RM1-950 medicine.disease Gout Rilonacept Clinical trial Canakinumab 030104 developmental biology lcsh:Therapeutics. Pharmacology Immunology adult-onset Still´s disease business medicine.drug anakinra |
| Zdroj: | Frontiers in Pharmacology Frontiers in Pharmacology, Vol 11 (2021) |
| ISSN: | 1663-9812 |
| Popis: | Polygenic autoinflammatory diseases (AIDs), such as systemic juvenile idiopathic arthritis (sJIA), adult-onset Still's disease, Kawasaki disease, idiopathic recurrent pericarditis (IRP), Behçet’s Syndrome, Crystal-induced arthropatihes such as gout or Calcium pyrophosphate deposition disease are characterized by the overexpression of inflammasome-associated genes, leading to a dysregulation of the innate immune response. The IL-1 cytokine family (IL-1α, IL-1β, IL-1Ra, IL-18, IL-36Ra, IL-36α, IL-37, IL-36β, IL-36g, IL-38, IL-33) was defined to be principally responsible for the inflammatory nature of polygenic AIDs. Several clinical trials were initiated, and IL-1 blockade has been proven to cause a rapid reduction of clinical symptoms and normalization of laboratory parameters in the majority of cases. Randomized, placebo-controlled, clinical trials, together with registry-based clinical trials and open-label, retrospective and prospective observational studies, supported the efficacy and safety of IL-1 inhibitors in the treatment of polygenic AIDs. Most of the current data are focused on the therapeutic use of anakinra, an IL-1 receptor antagonist, canakinumab, an anti-IL-1β monoclonal antibody, and rilonacept, a soluble decoy receptor. However, other promising agents, such as gevokizumab, IL-1β blocking monoclonal antibody, tadekinig alfa, a human recombinant IL-18-binding protein, and tranilast, an analog of a tryptophan metabolite, are currently being tested. Anakinra, canakinumab and rilonacept caused impressive improvements in both systemic and musculoskeletal symptoms. Furthermore, the anti-IL-1 therapy allowed corticosteroid tapering and, in some cases, even withdrawal. This article reviews the current IL-1 inhibitors and the results of all clinical trials in which they have been tested for the management of broad spectrum of polygenic AIDs. |
| Databáze: | OpenAIRE |
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