Compound Name:CanakinumabMolecular Target:Interleukin-1 beta (IL-1?)Molecular Structure:Human anti-human-IL-1? IgG1 monoclonal antibodyLicensed Indication:Treatment of CAPS, including Familial Cold Autoinflammatory Syndrome (FCAS), and Muckle-Wells Syndrome (MWS), in adults and children 4 years of age and olderManufacturer and/or Distributor:NovartisInitial FDA Approval2009SummaryCanakinumab (Ilaris) is a recombinant, human IgG1k monoclonal antibody directed at human-interleukin-1 beta (IL-1β). Canakinumab binds to human IL-1β and neutralizes its activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1α or act as an IL-1 receptor antagonist (IL-1ra). Canakinumab is used for the treatment of specific cryopyrin-associated periodic syndromes (CAPS), also known as cryopyrinopathies, autoinflammatory syndromes, or periodic fever syndromes. These rare genetic syndromes are generally caused by mutations in the NLRP3 [nucleotide-binding domain, leucine rich family (NLR), pyrin domain containing 3] gene (aka Cold-Induced Auto-inflammatory Syndrome-1 [CIAS1] gene), which encodes the protein cryopyrin. Cryopyrin is an important component of the inflammasome, a complex involved in regulation and activation of inflammatory cytokines. Certain mutations in NLRP3/CIAS1 result in an overactive inflammasome, and consequently excessive release of activated IL-1β that drives inflammation and the clinical features associated with CAPS. Canakinumab is administered subcutaneously every 8 weeks.

 Canakinumab was approved in 2009 by the FDA for the treatment of CAPS, including Familial Cold Auto-inflammatory Syndrome (FCAS), and Muckle-Wells Syndrome (MWS), in adults and children 4 years of age and older. In 2013, the FDA approved its use to treat active systemic juvenile idiopathic arthritis.
 Current investigative studies suggest canakinumab may be effective in Schnitzler Syndrome [double-blind placebo controlled], intractable urticaria refractory to omalizumab [you need to be related to Warren Buffett to try this on urticaria], Bechets disease and intractable pediatric uveitis.
 The major adverse reactions with canakinumab are infections, predominantly of the upper respiratory tract, and hypersensitivity. Concomitant use with TNF-blockers (e.g. adalimumab, etanercept, infliximab) is not recommended due to a theoretical increased risk of infection based on the experience with anakinra.

There was concern of macrophage activation syndrome in children with systemic JIA treated with canakinumab; however a review suggested no correlation. The expression of hepatic CYP450 enzymes may be suppressed by pro-inflammatory cytokines, such as IL-1b. Thus, CYP450 expression may be normalized when potent cytokine inhibitory therapy, such as canakinumab, is introduced. As a result, patients taking other products metabolized by the CYP450 system, particularly those products with a narrow therapeutic index, should be monitored closely. Canakinumab is expensive and costs $103,641 [68,883 British pound sterling] per year to treat a 20 kg child with SJIA, which is more than tocilizumab [7,987 British pound sterling/year = $12,020].References

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