Abstract
Autoinflammatory diseases (AIDs) represent a rare and heterogeneous group of disorders characterized by recurrent episodes of inflammation and a broad range of clinical manifestations. The most common symptoms involve recurrent fevers, musculoskeletal symptoms, and serositis; however, AIDs can also lead to life-threatening complications, such as macrophage activation syndrome (MAS) and systemic AA amyloidosis. Typical monogenic periodic fever syndromes include cryopyrin-associated periodic fever syndrome (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyper IgD syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). However, a number of other clinical entities, such as systemic juvenile idiopathic arthritis (sJIA), adult-onset Still’s disease (AOSD), Kawasaki disease (KD) and idiopathic recurrent pericarditis (IRP), display similar phenotypical and immunological features to AIDs. All these diseases are pathophysiologicaly characterized by dysregulation of the innate immune system and the central pathogenic role is attributed to 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, and IL-33). Therefore, reasonable therapeutic approaches aim to inhibit these cytokines and their pathways. To date, several anti-IL-1 therapies have evolved. Each drug differs in structure, mechanism of action, efficacy for the treatment of selected diseases, and side effects. Most of the available data regarding the efficacy and safety of IL-1 inhibitors are related to anakinra, canakinumab, and rilonacept. Other promising therapeutics, such as gevokizumab, tadekinig alfa, and tranilast are currently undergoing clinical trials. In this review, we provide sophisticated and up-to-date insight into the therapeutic uses of different IL-1 inhibitors in monogenic periodic fever syndromes.
Highlights
Autoinflammatory diseases (AIDs) represent a heterogeneous group of rare disorders characterized by chronic and/or recurring systemic inflammation
We conducted a comprehensive review of the literature on the efficacy and safety of IL-1 inhibition therapy including anakinra, rilonacept and canakinumab in cryopyrin-associated periodic fever syndrome (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), familial Mediterranean fever (FMF) and MKD/ HIDS were used as the key words in the search strategy
Novel classification criteria of CAPS based on the genotype and/or typical clinical manifestation have been proposed by Eurofever/PRINTO (Paediatric Rheumatology International Trials Organization) [62] familial cold autoinflammatory syndrome (FCAS), MuckleWells syndrome (MWS), and CINCA/NOMID are autosomal dominant diseases caused by a mutation of the NLRP3 gene, which causes the overproduction of IL-1b by cryopyrin inflammasomes [63]
Summary
Autoinflammatory diseases (AIDs) represent a heterogeneous group of rare disorders characterized by chronic and/or recurring systemic inflammation. Dapansutrile inhibits subsequent activation of IL-1b and is currently tested in the treatment of gout, autoimmune encephalitis and may carry a large potential in the treatment of AIDs [21, 22] Other novel compounds, such as peptides and small-molecule inhibitors of the NLRP3 inflammasome, are tested in multiple pre-clinical studies as modulators of IL-1 mediated inflammation [23,24,25]. Agents, such as diacerein, inzomelid or MCC950, are currently being tested in phase I/II clinical trials and as they affect the IL-1 cytokine family, they might be evaluated in the treatment of monogenic AIDs in the future [23]. We have separately introduced different aspects and results of observational studies, randomized placebo-controlled clinical trials and registry-based studies (Tables 1A–D)
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