Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition

Raphaela Goldbach-Mansky, Natalie J. Dailey, Scott W. Canna, Ana Gelabert, Janet Jones, Benjamin I. Rubin, H. Jeffrey Kim, Carmen Brewer, Christopher Zalewski, Edythe Wiggs, Suvimol Hill, Maria L. Turner, Barbara I. Karp, Ivona Aksentijevich, Frank Pucino, Scott R. Penzak, Margje H. Haverkamp, Leonard Stein, Barbara S. Adams, Terry L. MooreRobert C. Fuhlbrigge, Bracha Shaham, James N. Jarvis, Kathleen O'Neil, Richard K. Vehe, Laurie O. Beitz, Gregory Gardner, William P. Hannan, Robert W. Warren, William Horn, Joe L. Cole, Scott M. Paul, Philip N. Hawkins, Hang Pham Tuyet, Christopher Snyder, Robert A. Wesley, Steven C. Hoffmann, Steven M. Holland, John A. Butman, Daniel L. Kastner

Research output: Contribution to journalArticlepeer-review

753 Scopus citations


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 In 11 patients, anakinra was withdrawn at three months until a flare occurred.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

Original languageEnglish
Pages (from-to)581-592
Number of pages12
JournalNew England Journal of Medicine
Issue number6
StatePublished - 10 Aug 2006


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