Anakinra in patients with treatment-resistant adult-onset Still's disease: four case reports with serial cytokine measurements and a review of the literature.

Objective: To determine the efficacy of the interleukin (IL)-1-receptor antagonist (IL-1RA) anakinra in patients with adult-onset Still's disease (AOSD) refractory to standard treatments such as glucocorticosteroids (GC), immunosuppressive drugs, and tumor necrosis factor (TNF)-antagonists; to verify disease remission objectively by serial cytokine measurements; and to review the current literature on anakinra for this indication.

Methods: Four patients with AOSD--2 with acute flares of the chronic form of the disease and 2 with intermittent disease--were treated with prednisolone and methotrexate. One was also treated with several other immunosuppressive drugs including etanercept and infliximab. One patient had life-threatening symptoms (toxic megacolon, pneumonitis, disseminated intravascular coagulation) despite high-dose prednisolone. Treatment with anakinra 100 mg/d subcutaneously was initiated. White blood cells (WBC), C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), liver enzymes, ferritin levels, and serum cytokines were analyzed. The current literature on the efficacy of anakinra for AOSD is reviewed.

Results: Patients with chronic AOSD quickly responded to anakinra treatment (1 day to 3 days). GC could be tapered. ESR, CRP, WBC, ferritin, and liver enzymes returned to normal. Serum cytokine measurements revealed moderately elevated IL-1beta levels and highly elevated IL-18 levels in active disease, which normalized with anakinra. TNF-alpha and IL-6 were moderately elevated only in the 2 patients with chronic AOSD. In the literature, 17 similar cases have been reported to date.

Conclusions: Anakinra is effective in treatment-resistant and in life-threatening AOSD. IL-18 serum levels, in addition to CRP, ESR, liver enzymes, ferritin, and WBC, may be helpful in assessing disease activity and response to treatment.