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Abstract

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 1 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-1β (IL-1β), IL-1α, IL-6, IL-1 receptor antagonist, and IL-18 were elevated. Just prior to anakinra treatment, the WBC count was 14,600/mm3, the CRP level was 86 mg/liter, and the ferritin level was 573 ng/ml, with daily spiking fevers to 104°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/mm3 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/mm3, 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.