Abstract
IntroductionCryopyrin-associated periodic syndrome (CAPS) represents a spectrum of three auto-inflammatory syndromes, familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (NOMID/CINCA) with etiology linked to mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1β) release. CAPS is a rare hereditary auto-inflammatory disease, which may start early in childhood and requires a life-long treatment. Canakinumab, a fully human anti-IL-1β antibody, produces sustained selective inhibition of IL-1β. This study was conducted to assess the efficacy, safety, and pharmacokinetics of canakinumab in the treatment of pediatric CAPS patients.MethodsSeven pediatric patients (five children and two adolescents) with CAPS were enrolled in a phase II, open-label study of canakinumab in patients with CAPS. Canakinumab was administered at a dose of 2 mg/kg subcutaneously (s.c.) (for patients with body weight ≤ 40 kg) or 150 mg s.c. (for patients with body weight > 40 kg) with re-dosing upon each relapse. The primary efficacy variable was time to relapse following achievement of a complete response (defined as a global assessment of no or minimal disease activity and no or minimal rash and values for serum C-reactive protein (CRP) and/or serum amyloid A (SAA) within the normal range, < 10 mg/L).ResultsAll patients achieved a complete response within seven days after the first dose of canakinumab and responses were reinduced on retreatment following relapse. Improvements in symptoms were evident within 24 hours after the first dose, according to physician assessments. The estimated median time to relapse was 49 days (95% CI 29 to 68) in children who received a dose of 2 mg/kg. Canakinumab was well tolerated. One serious adverse event, vertigo, was reported, but resolved during treatment.ConclusionsCanakinumab, 2 mg/kg or 150 mg s.c., induced rapid and sustained clinical and biochemical responses in pediatric patients with CAPS.Trial registration numberClinicalTrials.gov: NCT00487708
Highlights
Cryopyrin-associated periodic syndrome (CAPS) represents a spectrum of three auto-inflammatory syndromes, familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (NOMID/CINCA) with etiology linked to mutations in the NLRP3 gene resulting in elevated interleukin-1b (IL-1b) release
Seven pediatric patients with CAPS were enrolled in a phase II, open-label study of canakinumab in patients with CAPS
All patients achieved a complete response within seven days after the first dose of canakinumab and responses were reinduced on retreatment following relapse
Summary
Cryopyrin-associated periodic syndrome (CAPS) represents a spectrum of three auto-inflammatory syndromes, familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (NOMID/CINCA) with etiology linked to mutations in the NLRP3 gene resulting in elevated interleukin-1b (IL-1b) release. Cryopyrin-associated periodic syndrome (CAPS) comprises a spectrum of rare inherited chronic auto-inflammatory disorders including familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), neonatal onset multisystem inflammatory disease (NOMID), known as chronic infantile neurological, cutaneous, and articular syndrome (CINCA). Common characteristics of these disorders include high-grade fever, urticarial rash, ocular manifestations such as conjunctivitis, sensorineural hearing loss and arthritis [1,2,3,4,5]. There is, a need for improved anti-IL-1b therapies for the management of CAPS and other auto-inflammatory conditions driven by overproduction of IL-1b
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