RT Journal Article
SR Electronic
T1 A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1714
OP 1719
DO 10.1136/annrheumdis-2013-204877
VO 74
IS 9
A1 Cailin H Sibley
A1 Andrea Chioato
A1 Sandra Felix
A1 Laurence Colin
A1 Abhijit Chakraborty
A1 Nikki Plass
A1 Jackeline Rodriguez-Smith
A1 Carmen Brewer
A1 Kelly King
A1 Christopher Zalewski
A1 H Jeffrey Kim
A1 Rachel Bishop
A1 Ken Abrams
A1 Deborah Stone
A1 Dawn Chapelle
A1 Bahar Kost
A1 Christopher Snyder
A1 John A Butman
A1 Robert Wesley
A1 Raphaela Goldbach-Mansky
YR 2015
UL http://ard.bmj.com/content/74/9/1714.abstract
AB Objective To study efficacy and safety of escalating doses of canakinumab, a fully human anti-IL-1β monoclonal antibody in the severe cryopyrin-associated periodic syndrome, neonatal-onset multisystem inflammatory disease (NOMID).Methods 6 patients were enrolled in this 24-month, open-label phase I/II study. All underwent anakinra withdrawal. The initial subcutaneous canakinumab dose was 150 mg (or 2 mg/kg in patients ≤40 kg) or 300 mg (or 4 mg/kg) with escalation up to 600 mg (or 8 mg/kg) every 4 weeks. Full remission was remission of patient-reported clinical components and measures of systemic inflammation and CNS inflammation. Hearing, vision and safety were assessed. Primary endpoint was full remission at month 6.Results All patients flared after anakinra withdrawal, and symptoms and serum inflammatory markers improved with canakinumab. All patients required dose escalation to the maximum dose. At month 6, none had full remission, although 4/6 achieved inflammatory remission, based on disease activity diary scores and normal C-reactive proteins. None had CNS remission; 5/6 due to persistent CNS leucocytosis. At the last study visit, 5/6 patients achieved inflammatory remission and 4/6 had continued CNS leucocytosis. Visual acuity and field were stable in all patients, progressive hearing loss occurred in 1/10 ears. Adverse events (AEs) were rare. One serious AE (abscess due to a methicillin-resistant Staphylococcus aureus infection) occurred.Conclusions Canakinumab at the studied doses improves symptoms and serum inflammatory features of NOMID, although low-grade CNS leukocytosis in four patients and headaches in one additional patient persisted. Whether further dose intensifications are beneficial in these cases remains to be assessed.ClinicalTrials.gov identifier NCT00770601.