Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition.

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 In 11 patients, anakinra was withdrawn at three months until a flare occurred.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

• Authors: 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 Moore, Robert 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, Tuyet Hang Pham, Christopher Snyder, Robert A Wesley, Steven C Hoffmann, Steven M Holland, John A Butman, Daniel L Kastner
• Journal: The New England journal of medicine (N Engl J Med) Vol. 355 Issue 6 Pg. 581-92 (Aug 10 2006) ISSN: 1533-4406 [Electronic] United States
• PMID: 16899778 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Copyright 2006 Massachusetts Medical Society.

Chemical References

• Carrier Proteins
• IL1RN protein, human
• Interleukin 1 Receptor Antagonist Protein
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• Receptors, Interleukin-1
• Sialoglycoproteins

Topics

• Adolescent
• Adult
• Carrier Proteins (genetics)
• Child
• Child, Preschool
• Female
• Hearing Loss (drug therapy)
• Humans
• Inflammation (drug therapy, genetics)
• Intellectual Disability
• Interleukin 1 Receptor Antagonist Protein
• Male
• Meningitis (drug therapy)
• Mutation
• NLR Family, Pyrin Domain-Containing 3 Protein
• Papilledema (drug therapy)
• Receptors, Interleukin-1 (antagonists & inhibitors)
• Sialoglycoproteins (adverse effects, therapeutic use)
• Syndrome
• Urticaria (drug therapy)