Ontology highlight
ABSTRACT: Background
Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.Methods
We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.Results
All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.Conclusions
Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations. (ClinicalTrials.gov number, NCT00069329 [ClinicalTrials.gov].).
SUBMITTER: Goldbach-Mansky R
PROVIDER: S-EPMC4178954 | biostudies-literature | 2006 Aug
REPOSITORIES: biostudies-literature
Goldbach-Mansky Raphaela R Dailey Natalie J NJ Canna Scott W SW Gelabert Ana A Jones Janet J Rubin Benjamin I BI Kim H Jeffrey HJ Brewer Carmen C Zalewski Christopher C Wiggs Edythe E Hill Suvimol S Turner Maria L ML Karp Barbara I BI Aksentijevich Ivona I Pucino Frank F Penzak Scott R SR Haverkamp Margje H MH Stein Leonard L Adams Barbara S BS Moore Terry L TL Fuhlbrigge Robert C RC Shaham Bracha B Jarvis James N JN O'Neil Kathleen K Vehe Richard K RK Beitz Laurie O LO Gardner Gregory G Hannan William P WP Warren Robert W RW Horn William W Cole Joe L JL Paul Scott M SM Hawkins Philip N PN Pham Tuyet Hang TH Snyder Christopher C Wesley Robert A RA Hoffmann Steven C SC Holland Steven M SM Butman John A JA Kastner Daniel L DL
The New England journal of medicine 20060801 6
<h4>Background</h4>Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.<h4>Methods</h4>We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an int ...[more]