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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Acknowledgement We are grateful to Mr. SM Kang for providing excellent technical assistance.
Disclosure of Interest None declared