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Refractory adult onset Still’s disease successfully treated with anakinra
  1. F M Vasques Godinho,
  2. M J Parreira Santos,
  3. J Canas da Silva
  1. Rheumatology Department, Hospital Garcia de Orta, Almada, Portugal
  1. Correspondence to:
    Dr F M Vasques Godinho
    Av Prof Torrado da Silva, Hospital Garcia de Orta, Almada, Portugal;

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Proinflammatory cytokines like tumour necrosis factor α (TNFα), interleukin (IL) 6, IL18, and IL1 have been implicated in the pathogenesis of several chronic rheumatic inflammatory diseases, including juvenile idiopathic arthritis and adult onset Still’s disease (AOSD).1–,5 The treatment of these diseases includes non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids and, in resistant cases, methotrexate (MTX), cyclophosphamide, sulfasalazine, and ciclosporin A6–,8 have been used. Over the past years, several cases of successful treatment with infliximab and etanercept in AOSD, refractory to conventional drugs, have been published.8,9


We report a favourable response to anakinra in a patient unresponsive to several disease modifying antirheumatic drugs (DMARDs) and TNFα blockers, requiring chronic high doses of steroids. The patient is a 32 year old woman diagnosed at the age 18 with AOSD, defined by the criteria of Yamaguchi et al.10 She was treated with NSAIDs, systemic steroids, and several DMARDs (MTX, sulfasalazine, and ciclosporin A) over a period of 10 years, but she had sustained disease with frequent flares requiring high doses of steroids (up to 1 mg/kg/day).

At the age of 28, she was referred to our rheumatology unit with persistent fever, arthritis, anaemia, leucocytosis, and raised serum level of C reactive protein, erythrocyte sedimentation rate (ESR), and ferritin despite treatment with prednisolone 30 mg/day, naproxen 1 g/day, and MTX 20 mg/week. At examination she had six tender and six swollen joints and reduced range of motion of the neck, wrists, and hips. Screening tests for infection were negative. She was treated with intravenous immunoglobulin (2 g/kg) and prednisolone, and MTX was increased up to 25 mg/week subcutaneously (SC), but only showed a partial response. At 2 months’ follow up the patient reported difficulty in walking, with increased hip pain. A pelvic x ray examination disclosed bilateral aseptic necrosis of the femoral heads and she was admitted for total bilateral hip arthroplasty.

In October 2000 infliximab was added to her treatment, initially at a dose of 3 mg/kg and increased to 5 mg/kg. Six months later she continued to have fever, arthritis (19 tender and two swollen joints) and a raised ESR (117 mm/1st h); infliximab was discontinued. Treatment was changed to etanercept, 25 mg SC, twice a week for 54 weeks, with little clinical response. Throughout this period she continued to have intermittent fever, arthritis, and raised serological inflammatory markers.

In October 2002 it was decided to attempt anakinra 100 mg/day SC in addition to MTX 25 mg/week SC, prednisolone 20 mg/day, and naproxen. An impressive improvement of the systemic features and joint disease occurred over the first weeks of treatment and the acute phase reactants returned to normal. Steroids could be reduced and discontinued. Anakinra was well tolerated and no adverse effects were seen. After 18 months of follow up the patient remains in full clinical remission, without steroids or NSAIDs (table 1).

Table 1

 Clinical evolution of the patient

This is, to our knowledge, the first reported case of successful treatment of AOSD with anakinra.


Although TNFα antagonists have revolutionised the treatment of refractory AOSD, some patients do not respond to this treatment. The dramatic response to anakinra in this case of AOSD refractory to conventional treatments and to anti-TNFα blockers, suggests that the inhibition of IL1 may be an important therapeutic target in some patients.


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