Biologic drugs in autoinflammatory syndromes

Purpose of the review: Inherited 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 topics: The 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-l-receptor antagonist (DIRA) is caused by mutations in the gene encoding for the interleukin-1 receptor antagonist (IL-1Ra). In this case the 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. (C) 2012 Elsevier B.V. All rights reserved.