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antagonist(1 to 2 mg per kilogram of body weight per day subcutaneously).In 11 patients,anakinra was withdrawn at three months until a flare occurred.The primary end points included changes in scores in a daily diary of symptoms,serum levels of amyloid A and C-reactive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. 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antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously) .In 11 patients, anakinra was withdrawn at three months until a flare occurred.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 amy yloid 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. Wielddrawal of anakinrarium resulted in relapse within days; retreatment led to rapid improvement. Here are 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.