Rapid responses to anakinra in patients with refractory adult-onset Still's disease

Objective. To assess the efficacy of anakinra treatment in patients with adult-onset Still's disease (AOSD) that is refractory to corticosteroids, methotrexate (MTX), and etanercept. Methods. Four patients with AOSD were treated with prednisone and MTX and 2 patients were also treated with etanercept for worsening symptoms and indicators of systemic inflammation. White blood cells (WBCs), C-reactive protein (CRP) levels and/or erythrocyte sedimentation rate, and ferritin levels were measured and, in I patient, serum creatinine levels were determined. Treatment with anakinra at 100 mg/day was initiated. Results. The index patient's disease was refractory to treatment with prednisone (30 mg/day) and MTX, with spiking fevers, rash, synovitis, a serum ferritin level of 8,400 ng/ml (normal <= 200), and a CRP level of 86 mg/liter (normal < 8). Levels of interleukin-1 beta (IL-1 beta), IL-1 alpha, IL-6, IL-1 receptor antagonist, and IL-18 were elevated. Just prior to anakinra treatment, 3 the WBC count was 14,600/mm(3) the CR-P level was 86 mg/liter, and the ferritin level was 573 ng/ml, with daily spiking fevers to 104 degrees F, rash, and swollen joints. Within hours of the first injection, the patient was afebrile and asymptomatic; within days, the WBC count, ferritin level, and CRP level decreased into the normal range. On 2 occasions, anakinra was withheld. Within a few days, the WBC count rose to > 20,000/mm(3) with prominent neutrophilia, the CRP level rose to > 200 mg/liter, and the ferritin level rose to > 3,000 ng/ml. Upon restarting anakinra, the patient became afebrile, the WBC count fell to 8,000/mm(3), the CRP level fell to < 3 mg/liter, and the ferritin level fell to < 300 ng/ml. Three additional patients with refractory AOSD who experienced rapid reductions in fever, symptoms, and markers of inflammation when treated with anakinra are reported. Conclusion. Refractory AOSD appears to be IL-1-mediated since anakinra decreases hematologic, biochemical, and cytokine markers and also produces rapid reductions in systemic and local inflammation. Reported efficacy of tumor necrosis factor-blocking therapies in AOSD may be due to a reduction in IL-1.