Neonatal-Onset Multisystem Inflammatory Disease Responsive to Interleukin-1β Inhibition

作者：Raphaela T. Goldbach‐Mansky, Natalie Dailey Garnes, Scott Canna, Ana Escarda Gelabert, Janet H. Jones, Benjamin I. Rubin, H Jeffrey Kim, Carmen C. Brewer, Christopher K. Zalewski, Edythe A. Wiggs, Suvimol Chirathivat Hill, Maria L Chanco Turner, Barbara Illowsky Karp, Ivona A Aksentijevich, Frank Pucino, Scott R Penzak, Margje H. Haverkamp, Leonard D. Stein, Barbara S. Adams, Terry L. Moore, Robert C. Fuhlbrigge, Bracha Shaham, James N. Jarvis, Kathleen M. O’Neil, Richard K. Vehe, Laurie Beitz, Gregory C. Gardner, William P. Hannan, Robert W. Warren, William F. Horn, Joe L. Cole, Scott M. Paul, Philip Nigel Hawkins, Tuyet Pham, Christopher Scott Snyder, ROBERT A. WESLEY, Steven C. Hoffmann, Steven M. Holland, John A. Butman, Daniel L. Kastner · 发表于：New England Journal of Medicine · 年份：2006 · DOI：10.1056/nejmoa055137 · 被引用次数：931 · 研究领域：Inflammasome and immune disorders、Kawasaki Disease and Coronary Complications、Autoimmune and Inflammatory Disorders Research

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 In 11 patients, anakinra was withdrawn at three months until a flare occurred.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 se...