Successful treatment of a small cohort of patients with adult onset of Still's disease with infliximab: first experiences

Abstract

Objective: To test the efficacy of infliximab in the treatment of patients with severe and active adult onset Still's syndrome (AOSD) despite conventional immunosuppressive therapy.

Patients and methods: Six patients with the diagnosis of AOSD according to the Yamagushi criteria of 1992 were treated with infliximab. All patients had severe disease with high clinical and serological activity. Patients were treated initially with high dose steroids or more intensive immunosuppressive therapy. Two patients had a history of multiple disease modifying antirheumatic drug (DMARD) treatments. One patient had a history of three years of AOSD with fever, chills, pleural and pericardial effusions, and hepatosplenomegaly. Despite these treatments, he developed increasing serological signs of inflammation and arthritis of both hips and peripheral joints. Another patient had a history of five years of AOSD with oligoarthritis, myalgias, and recurrent fever despite multiple DMARD treatment, including cyclophosphamide pulse therapy. Our patients with AOSD presented with massive polyarthralgias, polyarthritis, splenomegaly or hepatomegaly, the typical rash, sore throat, weight loss, serositis, continuing fever, leucocytosis, and raised C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and ferritin levels. Four patients with early onset of the disease, fulfilling the diagnostic criteria for AOSD and a clinical and serological high disease activity, were included in our pilot study without any further DMARD treatment apart from the initial steroid treatment. Reduction of established treatment, mainly with steroids, caused a relapse of the disease in all our patients. Patients then received 3-5 mg/kg infliximab on weeks 0, 2, and 6, continuing with intervals of 6-8 weeks depending on the patient's individual disease activity.

Results: In all patients, fever, arthralgias, myalgias, hepatosplenomegaly, and the rash resolved after the first courses of treatment with infliximab. All serological variables (CRP, ESR, hyperferritinaemia) returned to normal. After three courses of infliximab infusions, splenomegaly could not be detected in any of our patients. One caused by hip postarthritic osteoarthrosis, requiring hip replacement. After three courses of treatment with infliximab, splenomegaly could not be detected in any of our patients. Up to now, our patients have received infliximab infusion treatment for between five and 28 months. Throughout this period all patients have continued to benefit from this treatment, with improvement in their clinical symptoms, joint counts, and serological disease activity. One of our patients had a moderate infusion reaction during the second treatment. The infusion was discontinued for one hour and then was resumed with no further problems.

Conclusion: The disease improved remarkably in all six patients with AOSD after treatment with infliximab, also in the early stage of AOSD. These preliminary data suggest the potential therapeutic benefit of anti-tumour necrosis factor alpha treatment in AOSD.

Figure 1

Magnetic resonance imaging of a patient with both hips inflamed. Improvement in the synovitis is shown by reduction of the gadolinium uptake from week 0 to week 10 after treatment with 5 mg/kg infliximab.

Figure 2

Magnetic resonance imaging of a patient's left inflamed knee joint. The change in gadolinium uptake from week 0 to week 10 after treatment with 5 mg/kg infliximab is shown. The complete reduction of gadolinium uptake indicates a marked improvement of the synovitis.