Anakinra in Patients with Treatment-Resistant Adult-Onset Still’s Disease: Four Case Reports with Serial Cytokine Measurements and a Review of the Literature

ObjectiveTo 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.MethodsFour 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.ResultsPatients 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-1β levels and highly elevated IL-18 levels in active disease, which normalized with anakinra. TNF-α 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.ConclusionsAnakinra 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.