Critical appraisal of canakinumab in the treatment of adults and children with cryopyrin-associated periodic syndrome (CAPS)

Abstract

Abstract:The cryopyrin-associated syndromes (CAPS) include three autosomal-dominant syndromes, that are caused by a mutation in the NLRP3 gene on chromosome 1, encoding the cryopyrin protein. These syndromes, familial cold autoinflammatory syndrome, Muckle-Wells syndrome and neonatal-onset multisystem inflammatory disease, are characterized by urticaria-like rash, fever, central nervous system inflammation, an arthropathy and a risk of the development of amyloidosis in a respectively escalating degree of severity between the various syndromes. Recently the role of cryopyrin in the regulation of interleukin (IL)-1 production and activation was described and anti IL-1 therapies were found to be very effective in treating these syndromes. There are several types of anti IL-1 medications based on different mechanisms of antagonizing IL-1. This paper focuses on the efficacy and safety of canakinumab, a long-acting humanized anti IL-1 antibody, in treating these syndromes.

Renal amyloidosis in children

“…Progressive sensorineural hearing loss develops in the second and fourth decades. Amyloidosis develops in 25% of the cases [ 73 , 76 ].The onset of CINCA-NOMID is at or within several weeks of birth. It is characterized by urticaria-like rash, fever, chronic aseptic meningitis, eye findings including conjunctivitis, uveitis, and papillitis of the optic nerve.…”

“…Patients have typical morphological changes of short stature, frontal bossing, macrocephaly, saddle nose, short, thick extremities with clubbing of fingers, and wrinkled skin. If untreated, 20% die by age 20 years, and others develop amyloidosis [ 74 , 76 ].…”

“…Treatment in CAPS In FCAS and MWS, corticosteroids may be used but are needed frequently and may cause significant side-effects. Anti-IL-1 agents are very effective in alleviating symptoms and decreasing inflammation in all CAPS patients [ 76 – 78 ].…”