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Systemic-onset juvenile idiopathic arthritis (SOJIA), formerly called Still’s disease, is a subset of juvenile arthritis that describes patients with fever, rash, arthritis, serositis and visceromegaly. In up to 30% of cases the disease has a chronic course and management requires high doses of glucocorticoids, disease-modifying antirheumatic drugs (DMARD), tumour necrosis factor alpha (TNFα) inhibitors or anakinra.1–6 However, this therapeutic arsenal is unable to control the disease in all patients.
Recently, rituximab, a chimeric anti-CD20 monoclonal antibody, has been successfully used in two patients with refractory adult-onset Still’s disease.7 As the similarity of clinical and laboratory features present in SOJIA and adult-onset Still’s disease implies that these conditions have similar pathogenic mechanisms,1 2 we tested rituximab in three patients with severe active SOJIA who had an inadequate response or were intolerant to current treatment options. The patients’ main characteristics at rituximab treatment initiation and outcome data are summarised in table 1. In all cases the disease persisted into adulthood, and at the time of the study they presented with intermittent fever, rash, persistent destructive polyarthritis and recurrent serositis (one patient). They had all received at least four DMARD (range four to six), intravenous immunoglobulin, one or more TNFα inhibitor and anakinra, none of which proved to be successful.
Rituximab treatment consisted of two endovenous infusions of 1 g per treatment cycle (except in one patient, who received 500 mg in the first cycle as a result of weighing only 40 kg), separated by a 2-week interval (days 1 and 15). In one patient rituximab was administered alone, whereas in the other two cases it was given in combination with methotrexate. All patients received premedication (100 mg methylprednisolone or equivalent) to prevent infusion reactions.
The three patients showed a significant clinical improvement, with remission of the systemic symptoms (fever, rash and serositis). Arthritis improved partly in two cases, with re-treatment being required 6–7 months later; in the other patient, a low degree of activity was achieved and no further treatment was required until 12 months later. Clinical improvement was accompanied by a parallel improvement in biological markers of inflammation, although in none of the cases were the acute phase reactants normalised. The concomitant oral steroid dose could be reduced to more than half of the initial dose.
One of the patients presented with a severe hypersensitivity reaction during the second infusion of the second treatment cycle, but no other adverse effects were observed. None of the patients suffered severe bacterial or opportunistic infections; serum immunoglobulin levels remained within the normal limits during treatment in all cases.
Our preliminary results suggest that rituximab seems to be a useful therapeutic alternative in patients with active SOJIA in whom previous treatments (including TNFα antagonists and anakinra) have failed. Our experience is that rituximab produces a substantial clinical improvement (remission of the systemic symptoms and moderate European League Against Rheumatism response of the arthritis), although the disease does not enter into remission. Of interest, our experience with rituximab is similar to the French experience with IL-1 receptor antagonist treatment in SOJIA/adult-onset Still’s disease.6 In that study, the benefits with anti-IL-1 therapy seem to be fair in the systemic manifestations but reduced in the articular complaints.
Further studies are needed to determine the place of specific B-cell depletion in the treatment of refractory SOJIA.
Competing interests: None.
Ethics approval: Ethics approval was obtained.
Patient consent: Obtained.
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