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 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-1beta (IL-1beta), IL-1alpha, IL-6, IL-1 receptor antagonist, and IL-18 were elevated. Just prior to anakinra treatment, the WBC count was 14,600/mm(3), the CRP 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.


CONCLUSIONS
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.
Fitzgerald
Avril A
AA
University of Calgary, Calgary, Alberta, Canada.
Leclercq
Sharon A
SA
Yan
Alexander
A
Homik
Joanne E
JE
Dinarello
Charles A
CA
D000293:Adolescent; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D004351:Drug Resistance / Q000276:immunology; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology; D008297:Male; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology; D012795:Sialoglycoproteins / Q000627:therapeutic use*; D016706:Still's Disease, Adult-Onset / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
D018501:Antirheumatic Agents; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins