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AB0055 Cytokine Profiles of Korean Patients with Adult Onset Still's Disease Treated with Tumor Necrosis Factor Inhibitors
  1. S.T. Song,
  2. S. Lee,
  3. S.W. Lee,
  4. I.W. Sohn,
  5. H.-J. Jeong,
  6. D.-H. Yoo
  1. Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Republic Of

Abstract

Background Adult onset Still's disease (AOSD) is a rare inflammatory disorder of unknown etiology. Several studies have reported that pro-inflammatory cytokines including interleukin (IL)-1, IL-6, IL-18, tumor necrosis factor (TNF)-α, and interferon (INF)-γ, are involved in the pathogenesis of AOSD. Refractory AOSD patients have been treated successfully with anti-cytokine biologics.

Objectives Herein, to investigate predictors for therapeutic response of biologic drugs in refractory AOSD, we analyzed cytokines profiles in Korean patients with AOSD who were treated with anti-TNFα inhibitors.

Methods Twenty two AOSD patients treated with anti-TNFα agents were recruited from a university hospital for rheumatic diseases in Korea. The dosages of anti-TNFα (infliximab in 18 patients, etanercept in 4, and adalimumab in 3) were same as rheumatoid arthritis. White blood cells, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, ferritin levels, liver enzymes, and serum cytokines (TNFα, IL-1β, IL-6, IL-8, IL-17α, and INF-γ) and IL-2 receptor α in sera were analyzed by multiplex flowcytometry. A good response to anti-TNFα inhibitors was defined as decreased modified Pouchot score more than 2 score compared to initial treatment of anti-TNFα inhibitors. A no response to anti-TNFα inhibitors was defined as no decrease of modified Pouchot score. We used the Mann-Whitney test or Wilcoxon signed rank test for continuous variable and Fisher's exact test for categorical variables.

Results Six (27.3%) patients showed good response to anti-TNFα inhibitors and 3 (13.6%) patients showed partial response. Thirteen (59.1%) patients did not respond to anti-TNFα inhibitors. At starting time point of anti-TNFα inhibitors, levels of ferritin, TNFα, IL-1β, IL-6, and IFNγ in no responders (mean±SD 4,142.0±7,128.6 ng/mL (range 27–18,331), 6.9±10.5 pg/mL (0.0–27.9), 2.6±2.9 pg/mL (0.0–7.4), 16.9±18.7 pg/mL (1.2–221.6), and 13.2±9.1 pg/mL (4.9–30.9), respectively) seemed to be higher compared to those with good response (566.4±633.0 ng/mL (18–1,901), 13.8±24.3 pg/mL (0.0–67.0), 8.7±16.9 pg/mL (0.0–50.8), 77.1±157.8 (2.0–485.4), and 69.3±146 pg/mL (0.0–453.3), respectively), but without statistically significant differences between the 2 groups. We didn't raise the dosage of infliximab in no responders, in whom tocilizumab was used as second biologic therapy. Of those, seven (63.6%) patients showed improvement in clinical and laboratory findings.

Conclusions This study showed that AOSD patients who were refractory to anti-TNFα inhibitors might have distinct cytokine profiles. Therefore, dosage of anti-TNF agents in AOSD patients might be individualized according to pre-treatment cytokine profiles.

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  3. Fautrel B, Sibilia J, Mariette X, Combe B. Tumour necrosis factor alpha blocking agents in refractory adult Still's disease: an observational study of 20 cases. Ann Rheum Dis. 2005;64:262–6.

Acknowledgement We are grateful to Mr. SM Kang for providing excellent technical assistance.

Disclosure of Interest None declared

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