Canakinumab for treatment of cryopyrin-associated periodic syndrome.
BACKGROUND
Autoinflammatory syndromes such as cryopyrin-associated periodic syndromes (CAPS) place a heavy burden on affected individuals as well as on their families due to significant morbidity and increased mortality. The inflammatory response in CAPS is caused by an overwhelming activation of the pro-inflammatory cytokine IL-1, which was identified as a promising treatment target.


METHODS
This article focuses on the pathogenic background and different clinical manifestations in CAPS. Furthermore, the development program and characteristics of canakinumab, a recently approved fully human anti-IL-1β mAb for the treatment of CAPS, are described and compared to other available IL-1 blocking agents.


RESULTS
Canakinumab targets selectively human IL-1ß with high affinity and prevents the cytokine from interaction to its receptor and, thus, effectively blocks the inflammatory response in CAPS. In all studies performed, canakinumab showed a rapid improvement of symptoms of CAPS and a complete clinical response was achieved in most patients. Inflammatory markers such as C-reactive protein and serum amyloid-A protein were reduced to normal levels within few days. In comparison to other IL-1 blockers, canakinumab provides a longer plasma half-life and less injection site reactions.


CONCLUSIONS
Canakinumab offers the possibility of permanent disease control, almost symptom-free life, and hopefully less long-term morbidity and mortality in patients with CAPS.
Feist
Eugen
E
Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany. gerd.burmester@charite.de
Burmester
Gerd R
GR
D000210:Acute-Phase Reaction; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D002675:Child, Preschool; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D056587:Cryopyrin-Associated Periodic Syndromes / Q000453:epidemiology / Q000276:immunology / Q000628:therapy*; D004311:Double-Blind Method; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000276:immunology; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053583:Interleukin-1beta; C541220:canakinumab