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AB1161 Predictable and unexpected effects of tocilizumab in patients with systemic juvenile idiopathic arthritis
  1. I. Nikishina,
  2. M. Kaleda,
  3. O. Kostareva,
  4. S. Rodionovskaya
  1. Research Institute of Rheumatology Under Russian Academy of Medical Sciences, Moscow, Russian Federation

Abstract

Background It is known that Tocilizumab (TCZ) is effective option in systemic Juvenile idiopathic arthritis (sJIA). NNZ had “off label” status for children in Russia till December 2011, but with Ethics Committee approvement it used in clinical practice for most seriously affected sJIA patients (Pts).

Objectives To analyzed effects of TCZ on activity and other disease features in Ptswith active sJIA, who were received TCZ in our clinic from Nov 2009 to Jan 2012.

Methods TCZ was indicate to 23 Pts with sJIA (11 boys, 12 girls; mean age of 8.96, range 1.6–17.6 yrs; mean disease duration of 5.5, range 0.3–11,75 yrs) who had persistent disease activity in spite of adequate treatment, included NSAID, steroids, DMARDs (methotrexate (MTX) alone–7; MTX in combination with cyclosporine or leflunomide–16). After starting TCZ therapy second DMARD was cancelled andMTX therapy was continued in all children. 9 Pts were previously treated by biologics (7- TNF-inhibitors; 2-rituximab). Ongoing steroids was used in 19 Pts (meanprednisone dose - 0.35mg/kg/day, range 0,11–0.68), NSAIDs recievedall Pts. At baseline 22 Pts had active arthritis (mean number of active joints 14, range 3–30), 18 - systemic features, all Pts had high laboratory activity (mean CRP 108.25 mg/l, range 14.9-223 mg/l). We began TCZ use in a dose of 8 mg/kg intravenously every 4 weeks according to indications for adult RA patients. At 7 Pts the disease flare has developed for 15-20 day after infusion, therefore an interval have reduced till 2 weeks, the dose has been increased to 10-12 mg/kg.

Results The ACR Pedi 30,50,70,90 responds were achieved by 96%,48%,9%,0% of Pts at Week 4 (n=23), by 87%,87%,40%,7% at Week 12 (n=12), by 100%,92%,75%,17% at Week 24 (n=12), by 100%,100%,70%,30% at Week 52 (n=10), by 100%,100%,100%,83% at Week 76 (n=6), by 100%,100%,100%,80% at Week 104 (n=5) respectively. Systemic features and CRP level responded rapidly within few days, the arthritis responded later. Steady improvemaent allowed to decrease prednisolone dose inall Pts. Neutropenia was observed in 2 children during 2-3 days after infusion, but it was recovered without treatment. Growth increasing reached 5.56±2.9 cm/year (range 3-11) in Pts receiving TCZ longer than 1 year. 4 Pts had worsening of hip damage by X-ray, however at 1 patient we found X-ray improvement similar to that described by other authors (ref.1). We have also observed some unexpected effects: allergic reaction (acute urticaria during 2nd infusion in 2 Pts, Quincke’s edema during 3rd infusion - 1); non-durable sore throat on the 2nd day after infusion - 3. 3 Pts had symptoms of dramatic disease flare on 2-3 days after infusion (increasing of poliarthritis, rash, leucocytosis to 36000), state improved without treatment during 1-2 days. 2 children put the weight on (+31% and +84% added during 2 years).

Conclusions TCZ therapy is able to produce physical and emotional well-being of children with sJIA even in case of a very longstanding disease. In some Pts we have observed two types of disease flare - a resolved one on the 2-3d days after infusion and/or growing one on the 15-20 days after infusion. Both of them seem to be IL6-dependent phenomenon. Collecting data on unexpected but repeated effects of TCZ therapy is important for understanding of concealed TCZ actions.

  1. Y.Inaba et al. Ann Rheum Dis 2011; 70, 9; 1693-94.

Disclosure of Interest None Declared

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