1. Neonatal-Onset Multisystem Inflammatory Disease Responsive to Interleukin-1β Inhibition
- Author
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Barbara S. Adams, Frank Pucino, Natalie J Dailey, Richard K. Vehe, Leonard D. Stein, James N. Jarvis, Christopher K. Zalewski, Christopher Snyder, Bracha Shaham, Robert Wesley, Philip N. Hawkins, Kathleen M. O'Neil, Ivona Aksentijevich, T. Pham, Scott W. Canna, William Horn, Steven C. Hoffmann, Robert W. Warren, Maria L. Turner, Suvimol Hill, Carmen C. Brewer, Janet Jones, Laurie O Beitz, Joe L Cole, John A. Butman, Scott M. Paul, Margje H. Haverkamp, Scott R. Penzak, Raphaela Goldbach-Mansky, Gregory C. Gardner, H. Jeffrey Kim, Steven M. Holland, Robert C. Fuhlbrigge, Daniel L. Kastner, Terry L. Moore, Barbara I. Karp, Edythe Wiggs, Benjamin I. Rubin, Ana Gelabert, and William P Hannan
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Urticaria ,Sialoglycoproteins ,Gastroenterology ,Muckle–Wells syndrome ,Intellectual Disability ,Internal medicine ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Humans ,Meningitis ,Serum amyloid A ,Child ,Hearing Loss ,Inflammation ,Anakinra ,medicine.diagnostic_test ,business.industry ,Receptors, Interleukin-1 ,Cryopyrin-associated periodic syndrome ,Syndrome ,General Medicine ,medicine.disease ,Rash ,Rilonacept ,Interleukin 1 Receptor Antagonist Protein ,Neonatal onset multisystem inflammatory disease ,Child, Preschool ,Erythrocyte sedimentation rate ,Mutation ,Immunology ,Female ,medicine.symptom ,Carrier Proteins ,business ,Papilledema ,medicine.drug - Abstract
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.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 In 11 patients, anakinra was withdrawn at three months until a flare occurred.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.All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P0.001) 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 P0.001), 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.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].).
- Published
- 2006
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