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

@article{citeulike:3021574, 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 In 11 patients, anakinra was withdrawn at three months until a flare occurred.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].).}, address = {National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Md 20892, USA. goldbacr@mail.nih.gov}, author = {Goldbach-Mansky, R. and Dailey, N. J. and Canna, S. W. and Gelabert, A. and Jones, J. and Rubin, B. I. and Kim, H. J. and Brewer, C. and Zalewski, C. and Wiggs, E. and Hill, S. and Turner, M. L. and Karp, B. I. and Aksentijevich, I. and Pucino, F. and Penzak, S. R. and Haverkamp, M. H. and Stein, L. and Adams, B. S. and Moore, T. L. and Fuhlbrigge, R. C. and Shaham, B. and Jarvis, J. N. and O'Neil, K. and Vehe, R. K. and Beitz, L. O. and Gardner, G. and Hannan, W. P. and Warren, R. W. and Horn, W. and Cole, J. L. and Paul, S. M. and Hawkins, P. N. and Pham, T. H. and Snyder, C. and Wesley, R. A. and Hoffmann, S. C. and Holland, S. M. and Butman, J. A. and Kastner, D. L.}, citeulike-article-id = {3021574}, citeulike-linkout-0 = {http://dx.doi.org/10.1056/NEJMoa055137}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16899778}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16899778}, day = {10}, doi = {10.1056/NEJMoa055137}, issn = {1533-4406}, journal = {The New England journal of medicine}, keywords = {anakinra}, month = {August}, number = {6}, pages = {581--592}, posted-at = {2008-07-20 03:37:23}, priority = {2}, title = {Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition.}, url = {http://dx.doi.org/10.1056/NEJMoa055137}, volume = {355}, year = {2006} }

TY - JOUR ID - citeulike:3021574 L3 - citeulike-article-id:3021574 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. (ClinicalTrials.gov number, NCT00069329 [ClinicalTrials.gov].). IS - 6 JF - The New England journal of medicine SN - 1533-4406 AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Md 20892, USA. goldbacr@mail.nih.gov EP - 592 TI - Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. VL - 355 SP - 581 KW - anakinra AU - Goldbach-Mansky, R AU - Dailey, NJ AU - Canna, SW AU - Gelabert, A AU - Jones, J AU - Rubin, BI AU - Kim, HJ AU - Brewer, C AU - Zalewski, C AU - Wiggs, E AU - Hill, S AU - Turner, ML AU - Karp, BI AU - Aksentijevich, I AU - Pucino, F AU - Penzak, SR AU - Haverkamp, MH AU - Stein, L AU - Adams, BS AU - Moore, TL AU - Fuhlbrigge, RC AU - Shaham, B AU - Jarvis, JN AU - O'Neil, K AU - Vehe, RK AU - Beitz, LO AU - Gardner, G AU - Hannan, WP AU - Warren, RW AU - Horn, W AU - Cole, JL AU - Paul, SM AU - Hawkins, PN AU - Pham, TH AU - Snyder, C AU - Wesley, RA AU - Hoffmann, SC AU - Holland, SM AU - Butman, JA AU - Kastner, DL PY - 2006/08/10/ UR - http://dx.doi.org/10.1056/NEJMoa055137 ER -