Refractory adult onset Still's disease successfully treated with anakinra

Annals of the Rheumatic Diseases (Impact Factor: 10.38). 05/2005; 64(4):647-8. DOI: 10.1136/ard.2004.026617
Source: PubMed


Proinflammatory cytokines like tumour necrosis factor a
(TNFa), 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 antiinflammatory
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 TNFa 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
Letters 647
Downloaded from on 6 July 2006
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).
This is, to our knowledge, the first reported case of
successful treatment of AOSD with anakinra.
Although TNFa 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-TNFa blockers, suggests that the inhibition of IL1 may
be an important therapeutic target in some patients.
Authors’ affiliations
. . . . . . . . . . . . . . . . . . . . .
F M V Godinho, M J P Santos, J C da Silva, Rheumatology Department,
Hospital Garcia de Orta, Almada, Portugal
Correspondence to: Dr F M Vasques Godinho, Av Prof Torrado da
Silva, Hospital Garcia de Orta, Almada, Portugal; fatima_godinho@
Accepted 12 August 2004
Published Online First 16 September 2004

Download full-text


Available from: Maria Jose Santos,
  • Source
    • "Regarding concomitant oral corticosteroid usage, anakinra was shown to be an effective steroid-sparing agent. In agreement with the already reported literature, the use of anakinra allowed fast steroid tapering in responders and total discontinuation of steroid intake in approximately half of them [13,14,17-19]. Moreover, four patients did not require any corticosteroid therapy during the whole follow up. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To assess the efficacy and safety of the interleukin-1 receptor (IL-1R) inhibitor anakinra in adult patients with refractory Still's disease. Twenty-five patients (13 males and 12 females, median age 32 years, median disease duration seven months) with Still's disease were treated with subcutaneous injections of anakinra (100 mg/day). Treatment was given as adjunct therapy in 16 patients and as standalone in 9 patients for a median time of 15 months (range 1.5-71). The clinical and laboratory parameters during follow-up were recorded. In 84% of patients the clinical activity resolved completely within a few days (median time 0.2 months), and response was maintained until the last visit in all but one patient. A complete response of all disease-related symptoms (clinical and laboratory) occurred subsequently within a median time of three months in 80% of patients. A partial clinical and laboratory improvement was shown in 12% and 16% of patients, respectively. The Visualized Analogue Scale and Health Assessment Questionnaire scores significantly decreased during treatment. The proportion of patients achieving the American College of Rheumatology 20 (ACR20) score (20% improvement) was 82% at one month and improved to 100% at one year. The mean oral corticosteroid dose was significantly reduced at each visit. Anakinra was discontinued due to unresponsiveness in one patient and due to relapsing disease in another. Treatment was also withdrawn in three patients with severe skin reactions (urticaria). Seven patients experienced an infection during follow-up. The rapid and sustained response in the majority of our patients encourages the use of anakinra in adults with Still's disease.
    Arthritis research & therapy 06/2011; 13(3):R91. DOI:10.1186/ar3366 · 3.75 Impact Factor
  • Source

    Annals of the Rheumatic Diseases 11/2004; 63(suppl_2). DOI:10.1136/ard.2004.029272 · 10.38 Impact Factor
  • Source

    Annals of the Rheumatic Diseases 05/2005; 64(4):646-7. DOI:10.1136/ard.2004.029009 · 10.38 Impact Factor
Show more