UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Goldbach-Mansky, R; Dailey, NJ; Canna, SW; Gelabert, A; Jones, J; Rubin, BI; Kim, HJ; ... Kastner, DL; + view all (2006) Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition. NEW ENGL J MED , 355 (6) 581 - 592. Green open access

[thumbnail of 8602.pdf]
Preview
PDF
8602.pdf

Download (284kB)

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 In 11 patients, anakinra was withdrawn at three months until a flare occurred.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

Type: Article
Title: Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition
Open access status: An open access version is available from UCL Discovery
Keywords: NF-KAPPA-B, MUCKLE-WELLS-SYNDROME, AUTOINFLAMMATORY DISEASES, ACTIVATE CASPASE-1, FEBRILE RESPONSE, ANAKINRA, MUTATIONS, CYTOKINES, GENE, ASC
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/8602
Downloads since deposit
393Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item