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The combination of IL-6 and its soluble receptor is associated with the response of rheumatoid arthritis patients to tocilizumab

Seminars in Arthritis and Rheumatism Nov 07, 2017

Diaz-Torne C, et al. - The goal of this study was to combine IL-6 and soluble IL-6R (sIL-6R) levels to recognize groups of responses. The current study showed that rheumatoid arthritis (RA) patients could be easily stratified prior to therapeutic intervention with two molecules associated with the pathway blocked by tocilizumab. G1 patients, who had the best response to tocilizumab, had the highest level of IL-6 and the lowest level of sIL-6 R.

Methods

  • Heparinized blood and clinical information from 63 RA patients were gathered before treatment and after three and six months.
  • Two-step clustering (SPSS v.18) was utilized to establish the connection between IL-6 and sIL-6R.
  • Then, they compared European League Against Rheumatism (EULAR) response criteria with remission achievement in the groups of patients.

Results

  • Three statistical significant clusters of RA patients (i.e., g1, g2, and g3) were characterized by serum concentrations of IL-6 and sIL-6R at baseline.
  • All groups of RA patients had higher IL-6 and sIL-6R levels than healthy donors.
  • The levels of IL-6 expressed as median (IQR) in g1 patients were 124(90–183) pg/ml, in g2 12.3(4.4-24) pg/ml, and in g3 60.1(30-146) pg/ml (p<0.001).
  • The levels of sIL-6R expressed as mean±sd in g1 patients were 250.5±72 ng/ml, in g2 269.1±125 ng/ml, and in g3 732.7±243 ng/ml(p<0.001).
  • Disease activity score (DAS)28, C-reactive protein, and erythrocyte sedimentation rate were comparable in the three groups at baseline.
  • Disease duration in g3 was the longest (median(IQR) years: g1=11(5–15), g2=12(8-20), and g3 23(16-26); p=0.006), with years of disease evolution being correlated with sIL-6R levels (R=0.417, p<0.001).
  • Simple and Clinical Disease Activity Index (SDAI and CDAI) reduced significantly in the three groups.
  • However, EULAR response criteria and remission achievement at 6m was different in the three groups (p=0.03, p=0.04 respectively).
  • Seventeen out of the 18 patients in g1 had a good or moderate response to tocilizumab.
  • Conversely, the percentage of patients with no response to tocilizumab was higher in g3 than in g1 and g2.
  • They also observed different changing patterns of IL-6 and sIL-6R levels among the three groups.

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