Efficacy of anakinra in a case of refractory Still disease.

Adult onset still disease (AOSD) is usually treated with nonsteroidal anti-inflammatory (NSAIDs), corticosteroids, and methotrexate (MTX). In refractory forms, intravenous immunoglobulin (IVIg), cyclosporin A, or anti–TNF are used as also reported in this journal. These second line treatments may also be ineffective or induce side effects. Recently, anakinra, a specific antagonist to human interleukin-1 (IL-1) receptors, has been used in the refractory forms of AOSD. We report the case of a 33-year-old patient diagnosed with AOSD in 2003 according to the criteria of Yamaguchi et al. Initial diagnostic features were fever of 39°C, polyarthralgias, rash, leukocytosis of 15,000/mm with greater than 80% PMN, sore throat, and liver dysfunction. Follow-up showed a favorable outcome with prednisone (1 mg/kg/d), but symptoms relapsed when steroids were reduced below 25 mg/d. From November 2003 to December 2005, we prescribed MTX, IVIg, infliximab, and etanercept, but the patient’s symptoms remained dependent on high doses of corticosteroids and were only partially improved (Table 1). In January 2006, while taking prednisone 1 mg/kg/d, the patient still complained of diffuse arthralgias and fever, persisting after boluses of methylprednisolone. In June 2006, the patient was admitted for fever 39°C, night sweats, and diffuse arthralgias involving wrists, elbows, and hips. White cell count was 30,000 /mm, ferritin 920 g/L (glycosylated ferritin 18%), and CRP 142 mg/L. Because of steroid dependence, cyclosporin A was given 140 mg twice daily and a slight clinical improvement was observed. But 5 days later, the patient presented nonconstrictive pericarditis confirmed by cardiac ultrasound. Simultaneously, serum creatinine was measured 250 mol/L. Cyclosporin was discontinued, and methylprednisolone associated with aspirin and colchicine were introduced. A few days later, etanercept (25 mg SC twice a week) was given but had to be discontinued after the fourth injection due to an acute episode of congestive heart failure. The signs of congestive heart failure regressed after symptomatic treatment in the intensive care unit and discontinuation of etanercept. Because the biologic and clinical signs of active AOSD persisted, the patient was given subcutaneous anakinra 100 mg/d in association with MTX 35 mg/wk SC. Within 48 hours, arthralgias and fever resolved. The CRP fell to 7 mg/L, and the white-cell count fell to 20,000 after 4 injections. The patient remained asymptomatic after 7 months of treatment by anakinra and prednisone could be reduced to 15 mg/kg/d (Table 1). In this clinical case, anakinra was prescribed because corticosteroids, MTX, cyclosporin A, and anti–TNF failed to control AOSD activity. Cyclosporin and etanercept had to be discontinued because they had induced serious secondary events, respectively acute renal failure and congestive heart failure, already described with anti-TNF . Anakinra rapidly improved our patient’s clinical condition, was well tolerated and no adverse effects were seen. Efficacy of anakinra in refractory AOSD was reported in 5 patients, by Rudinskaya and Trock in 2003 and by Vasques Godinho et al and Fitzgerald et al. The persistent favorable outcome after 7 months of follow-up with anakinra, despite reduced doses of prednisone, seems encouraging and confirms sustained efficacy and good tolerance of this drug. In conclusion, anakinra appears to constitute a safe and efficient therapy in severe, refractory forms of AOSD. Considering our observation and previous reports, it could be discussed to give anakinra before anti-TNF drugs.