TY - JOUR
T1 - Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition
AU - Goldbach-Mansky, Raphaela
AU - Dailey, Natalie J.
AU - Canna, Scott W.
AU - Gelabert, Ana
AU - Jones, Janet
AU - Rubin, Benjamin I.
AU - Kim, H. Jeffrey
AU - Brewer, Carmen
AU - Zalewski, Christopher
AU - Wiggs, Edythe
AU - Hill, Suvimol
AU - Turner, Maria L.
AU - Karp, Barbara I.
AU - Aksentijevich, Ivona
AU - Pucino, Frank
AU - Penzak, Scott R.
AU - Haverkamp, Margje H.
AU - Stein, Leonard
AU - Adams, Barbara S.
AU - Moore, Terry L.
AU - Fuhlbrigge, Robert C.
AU - Shaham, Bracha
AU - Jarvis, James N.
AU - O'Neil, Kathleen
AU - Vehe, Richard K.
AU - Beitz, Laurie O.
AU - Gardner, Gregory
AU - Hannan, William P.
AU - Warren, Robert W.
AU - Horn, William
AU - Cole, Joe L.
AU - Paul, Scott M.
AU - Hawkins, Philip N.
AU - Tuyet, Hang Pham
AU - Snyder, Christopher
AU - Wesley, Robert A.
AU - Hoffmann, Steven C.
AU - Holland, Steven M.
AU - Butman, John A.
AU - Kastner, Daniel L.
PY - 2006/8/10
Y1 - 2006/8/10
N2 - 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 In 11 patients, anakinra was withdrawn at three months until a flare occurred.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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33746876396&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa055137
DO - 10.1056/NEJMoa055137
M3 - Article
C2 - 16899778
AN - SCOPUS:33746876396
SN - 0028-4793
VL - 355
SP - 581
EP - 592
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 6
ER -