Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta 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 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, 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
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 In 11 patients, anakinra was withdrawn at three months until a flare occurred.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].).
Conflict of interest statement
Dr. Stein reports having received consulting and lectures fees from Amgen and Genentech and research support from Amgen and Abbott; Dr. Moore, lecture fees from Amgen; Dr. Vehe, lecture fees from Amgen and research support from Abbott; and Dr. Cole, consulting fees from Abbott and lecture fees from Amgen. Amgen produces and distributes the medication evaluated in this study. No other potential conflict of interest relevant to this article was reported.
Copyright 2006 Massachusetts Medical Society.
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Source: PubMed