Rapid and Sustained Long- Term Efficacy and Safety of Canakinumab in Patients With Cryopyrin- Associated Periodic Syndrome Ages Five Years and Younger

OBJECTIVE: To assess longer-term efficacy and safety of canakinumab and the response to vaccination in children aged ≤5 years with cryopyrin-associated periodic syndrome (CAPS). METHODS: CAPS patients (aged ≤5 years) received 2mg/kg canakinumab subcutaneously every 8 weeks; patients with neonatal onset multisystem inflammatory disease (NOMID), received a starting dose of 4 mg/kg in this open-label trial. Efficacy was evaluated using physician's global assessment (PGA), and serum levels of C-reactive protein (CRP) and amyloid A (SAA). Adverse events (AEs) were collected. Vaccination response was evaluated using post-vaccination antibody titers at 4 and 8 weeks after immunization. RESULTS: Of the 17 patients enrolled, 12 (71%) had Muckle-Wells syndrome, 4 (24%) had NOMID, and 1 (6%) had familial cold autoinflammatory syndrome. All patients (17/17) were complete responders to canakinumab. PGA improved, and 65% of patients had absent auto-inflammatory disease at the end of study. Median CRP levels decreased over time. No such change was evident in SAA levels. During the extension study, post-vaccination antibody titers increased above protective levels in 16/17 (94%) assessable vaccinations. Ten (59%) patients had AEs suspected to be related to canakinumab; 8 (47%) experienced at least 1 serious AE. None of the AEs/SAEs required interruption of canakinumab therapy. CONCLUSION: Canakinumab effectively maintained efficacy through 152 weeks and appears to have no effect on the ability to produce antibodies against standard childhood killed vaccines. Safety profile of canakinumab was consistent with previous studies, supporting long-term use of canakinumab for CAPS in children < 5 years of age. This article is protected by copyright. All rights reserved