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
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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

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