8 research outputs found
Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition
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 In 11 patients, anakinra was withdrawn at three months until a flare occurred.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
Adalimumab with and without Methotrexate in Juvenile Rheumatoid Arthritis
BACKGROUND
Tumor necrosis factor (TNF) has a pathogenic role in juvenile rheumatoid arthritis.
We evaluated the efficacy and safety of adalimumab, a fully human monoclonal anti-
TNF antibody, in children with polyarticular-course juvenile rheumatoid arthritis.
METHODS
Patients 4 to 17 years of age with active juvenile rheumatoid arthritis who had previously
received treatment with nonsteroidal antiinflammatory drugs underwent stratification
according to methotrexate use and received 24 mg of adalimumab per square
meter of body-surface area (maximum dose, 40 mg) subcutaneously every other week
for 16 weeks. We randomly assigned patients with an American College of Rheumatology
Pediatric 30% (ACR Pedi 30) response at week 16 to receive adalimumab
or placebo in a double-blind fashion every other week for up to 32 weeks.
RESULTS
Seventy-four percent of patients not receiving methotrexate (64 of 86) and 94% of
those receiving methotrexate (80 of 85) had an ACR Pedi 30 response at week 16 and
were eligible for double-blind treatment. Among patients not receiving methotrexate,
disease flares (the primary outcome) occurred in 43% of those receiving adalimumab
and 71% of those receiving placebo (P = 0.03). Among patients receiving methotrexate,
flares occurred in 37% of those receiving adalimumab and 65% of those receiving
placebo (P = 0.02). At 48 weeks, the percentages of patients treated with methotrexate
who had ACR Pedi 30, 50, 70, or 90 responses were significantly greater for
those receiving adalimumab than for those receiving placebo; the differences between
patients not treated with methotrexate who received adalimumab and those
who received placebo were not significant. Response rates were sustained after 104
weeks of treatment. Serious adverse events possibly related to adalimumab occurred
in 14 patients.
CONCLUSIONS
Adalimumab therapy seems to be an efficacious option for the treatment of children with juvenile rheumatoid arthritis. (ClinicalTrials.gov number, NCT00048542.