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FRI0241 The effect of abatacept on cytokine profile in patients with rheumatoid arthritis
  1. MA Borisova,
  2. GV Lukina,
  3. Y Sigidin,
  4. EL Luchihina,
  5. DE Karateev,
  6. A Novikov,
  7. E Alexandrova,
  8. E Aronova,
  9. S Glukhova,
  10. E Nasonov
  1. Nasonova Reserch Institute of Rheumatology, MOSCOW, RUSSIA, Moscow, Russian Federation

Abstract

Background Pathological activation of T-cells with the overproduction of pro-inflammatory cytokines is playing a major role in the pathogenesis of rheumathoid arthritis (RA). The influence of the selective co-stimulation modulator abatacept (ABA) on the dynamics of cytokine profile in patients with RA is not fully understood.

Objectives To assess the changes in cytokine profile in patients treated with ABA.

Methods 44 patients with RA and an inadequate response to synthetic DMARDs or biologics were enrolled in the study. Most of them were middle aged females (46,9±13,9 years) with median RA duration 2 years (1,4–3), high disease activity (DAS28=5,2±0,8), RF-positive (80%) and ACPA-positive (79,5%). 16 healthy individuals were included in the study as control. The serum levels of IL-1, IL-6, IL-17, TNF-α, VEGF, IP-10 (pg/ml) were measured by ELISA immunoassay, YKL-40 by MicroVue immunoassay at baseline and 24 weeks. Disease activity was measured by DAS28, results were assessed every 12 weeks by EULAR criteria. ABA was administered intravenously every 4 weeks.

Results Levels of IL-6 (2.4 (1,1–6,4) vs 0.7 (0,62–1,0), p=0,0002), YKL-40 (97 (68,4–97, 9) vs. 64 (52,4–107,5), p=0,03), IP-10 (21 (12,9–49,8) vs 14 (9,2–15,2), p=0,005) were significantly higher in patients with RA compared to control. ABA significant reduced disease activity already after 12 weeks of therapy (p<0,05). After 24 weeks of ABA therapy good and moderate response by EULAR criteria was achieved in 86%, low disease activity by DAS28 in 52%. By the 6-th month ABA significant decreased levels of IL-6 (1,29 (0,9–2,2, p=0,0006), IP-10 (14 (7,5–28), p=0.007) as well as MMP3: before 30.1 (13–82), after 24 weeks 10 (7.4–55), p=0.0003 and RF: before 218 (9.6–187), after 24 weeks 159 (9.7–155), p=0.02. Lowering of the IL-6 (r=0,5) and IP-10 (r=0,32) levels were significantly (p<0.05) associated with a decrease of DAS28.

Conclusions ABA therapy leads to a significant reduction in serum levels of IL-6, IP-10, MMP3 and RF. The serum levels of IL-6 and IP-10 correlate with decrease activity of RA.

Disclosure of Interest None declared

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