| 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-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. 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. |
| Authors | Avril A Fitzgerald, Sharon A Leclercq, Alexander Yan, Joanne E Homik, Charles A Dinarello
(Affiliation: University of Calgary, Calgary, Alberta, Canada.)
|
| Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 52
Issue 6
Pg. 1794-803
(Jun 2005)
ISSN: 0004-3591 United States |
| PMID | 15934079
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- Antirheumatic Agents
- IL1RN protein, human
- Interleukin 1 Receptor Antagonist Protein
- Interleukin-1
- Receptors, Interleukin-1
- Sialoglycoproteins
|
| Topics |
- Adolescent
- Adult
- Antirheumatic Agents
(therapeutic use)
- Drug Resistance
(immunology)
- Female
- Humans
- Interleukin 1 Receptor Antagonist Protein
- Interleukin-1
(immunology)
- Male
- Receptors, Interleukin-1
(antagonists & inhibitors, immunology)
- Sialoglycoproteins
(therapeutic use)
- Still's Disease, Adult-Onset
(drug therapy, immunology)
- Treatment Outcome
|
