Biologic drugs in autoinflammatory syndromes

Purpose of the reviewInherited autoinflammatory syndromes are conditions caused by mutations of proteins playing a pivotal role in the regulation of the innate immunity leading to an uncontrolled inflammation. The understanding of the molecular pathways involved in these disorders has shed a new light on the pattern of activation and maintenance of the inflammatory response and disclosed new molecular therapeutic targets. In this review we give a start of the art of the use of biologics in these disorders.Main topicsThe dramatic response to anti IL-1 drugs in cryopyrin-associated periodic syndromes represents the brightest example of the possibility to completely dampen inflammation in these severe disorders with the selective blockade of a single pivotal cytokine. Periodic fevers are characterized by recurrent episodes of fever, usually treated with on demand steroids. However the increasing frequency of fever episodes or the development of a chronic disease course may require a continuous long-term treatment, with anti-TNF or IL-1 blockers in mevalonate kinase deficiency and TNF-receptor associated periodic syndrome. Anti-IL-1 treatment is also effective in FMF patients resistant or partially responsive to colchicine.The deficiency of the interleukin-1‐receptor antagonist (DIRA) is caused by mutations in the gene encoding for the interleukin-1 receptor antagonist (IL-1Ra). In this case t he recombinant IL-1Ra (anakinra) is the treatment of choice.Due to their extreme rarity the response to the available biologic drugs in other autoinflammatory diseases is still largely anecdotal.

► Autoinflammatory syndromes are caused by a dysregulation of the innate immunity.
► NLRP3 inflammasome is a multi-protein complex that regulates the activation and secretion of IL-1.
► NLRP3-mutated patients show an IL-1β hyper-secretion and respond to IL-1 blockers.
► DIRA is due to a defective production of IL-1Ra and is controlled by anakinra.
► Anti IL-1 blockers are effective in other autoinflammatory diseases.