{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:38:17Z","timestamp":1790775497099,"version":"4.1.0"},"reference-count":162,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009553","name":"Agentura Pro Zdravotnick\u00fd V\u00fdzkum \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Polygenic autoinflammatory diseases (AIDs), such as systemic juvenile idiopathic arthritis (sJIA), adult-onset Still's disease, Kawasaki disease, idiopathic recurrent pericarditis (IRP), Beh\u00e7et\u2019s 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-1\u03b1, IL-1\u03b2, IL-1Ra, IL-18, IL-36Ra, IL-36\u03b1, IL-37, IL-36\u03b2, 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-1\u03b2 monoclonal antibody, and rilonacept, a soluble decoy receptor. However, other promising agents, such as gevokizumab, IL-1\u03b2 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.<\/jats:p>","DOI":"10.3389\/fphar.2020.619273","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T08:01:35Z","timestamp":1611648095000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Interleukin-1 Blockade in Polygenic Autoinflammatory Disorders: Where Are We now?"],"prefix":"10.3389","volume":"11","author":[{"given":"Hana","family":"Malcova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Milota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Strizova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dita","family":"Cebecauerova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilja","family":"Striz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sediva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Horvath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1080\/1744666X.2017.1232165","article-title":"Kawasaki disease: etiopathogenesis and novel treatment strategies","volume":"13","author":"Agarwal","year":"2017","journal-title":"Expet Rev. 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