• Comparison of group mean of total disease diary score before compared to after treatment (3-4 mo); mean change in the area under the curve in SAA in patients before and 3-4 mo after tx as well as before and after drug withdrawal. [ Time Frame: 16-17 weeks ] [ Designated as safety issue: No ]
  

Drug: Anakinra
N/A

This is a multi-center pilot study using the IL-1 receptor antagonist anakinra to treat children with Neonatal Onset Multisystem Inflammatory Disease (NOMID), also known as chronic infantile neurological, cutaneous and arthropathy (CINCA) syndrome. NOMID/CINCA syndrome is a rare genetic systemic auto-inflammatory disease that is characterized by a triad of symptoms, including a persistent urticaria-like skin rash, an arthropathy associated with patellar and epiphyseal osseous overgrowth, and neurological manifestations, including chronic aseptic meningitis, optic disc edema, high frequency hearing loss, and mental retardation. Spontaneous genetic mutations in the NACHT domain of CIAS1, a gene located on chromosome 1, have been recently identified in about half of the patients with NOMID/CINCA syndrome. CIAS1 encodes a protein, cryopyrin that is associated with up-regulation of IL-1 production in vitro, which has formed the rationale to target the IL-1 pathway in children with NOMID. We plan to enroll a total number of 20 patients into this study. During a 3-week enrollment period before initiating therapy, we will collect self/parent reported daily diary data and serological samples on 3 occasions one week apart, to determine baseline disease activity. These data may be gathered by collaborating centers. At the end of the observation period, patients will be admitted to the NIH for a standardized clinical evaluation and initiation of treatment with anakinra administered at 1mg/kg/day by regular daily subcutaneous injections (study phase 1). Patients will be re-evaluated after one month and every month thereafter. If patients do not fulfill improvement criteria at 1 month, the dose will be escalated at 2.0 mg/kg/day with a maximum dose of 200 mg/day, while patients fulfilling response criteria will maintained on a 1mg/kg/dose (study phase 2). At three to four months, patients enter phase 3 of the study. Patients with stable disease and significant improvement will have drug withheld for 7 days during an observed hospital visit. Inflammatory parameters such as ESR, CRP and serum amyloid A (SAA) levels at the end of this phase will be compared to levels on treatment prior to withdrawal. The clinical improvement at 3-4 months and the change in serum amyloid A levels (a sensitive inflammatory marker) from before treatment to 3-4 months post treatment, change in SAA levels after 7 days of drug withdrawal, and drug safety are the primary clinical outcomes of this study. The withdrawal phase of the study was discontinued after 11 patients were withdrawn. After one week of drug withdrawal, anakinra will be re-started at the same dose as before drug was withdrawn. To assess long-term safety and efficacy, all patients will be observed during this open label extension phase of the study (phase 4) until they have received 12 months of anakinra. Clinical and laboratory parameters will be used to assess safety and efficacy throughout the trial. All patients will be seen every 6 months and annually (as calculated from initiation of anakinra treatment) to further evaluate safety and long term outcomes (phase 5). During the open ended extension phase of the study (phase 5), patients who have residual clinical or laboratory evidence of active inflammation despite taking 3 mg/kg/day of anakinra may have their dose increased in 0.5 mg/kg/day increments up to a maximum dose of 5 mg/kg/day, if clinically necessary. In addition, since no data on the pharmacokinetics of anakinra in pediatric patients is available with doses exceeding 2 mg/kg/day, we plan to determine the pharmacokinetics of anakinra with each dose escalation.