Method: In 42 RA patients (27 in the TCZ group, 15 in the TNF-inhibitor group) , serum concentrations of IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p70), IL-13, IL-17, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, interferon (INF) g, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1β, TNFα, chemokine (C-C motif) ligand (CCL)-20, IL-23 and TNF-like weak inducer of apoptosis (TWEAK) before treatment (M0) and after 6 months of treatment (M6) were measured by the multiplex method and ELISA. Clinical response was evaluated with disease activity score 28 using the C-reactive protein (DAS28-CRP) and European League against Rheumatism (EULAR) response criteria.
Result: DAS28-CRP was 4.7 ± 0.9 (mean ± SD) in the TCZ group and 5.1 ± 1.3 in the TNF-inhibitor group (p=0.16) at M0. The ratio of good responders / moderate responders / no responders at M6 was 16/9/2 in the TCZ group and 4/7/4 in the TNF-inhibitor group, respectively. Analysis of the cytokine profiles at M0 and M6 in good responders or moderate responders revealed that T-cell-related cytokines were inhibited mainly in the TCZ group, while chemokines were inhibited mainly in the TNF-inhibitor group (Table). When the cytokines that decreased to less than 40% at M6 were examined in good responders (TCZ group: 16, TNF-inhibitor group: 4), this trend was more pronounced in both groups (Table). Interestingly, the results of a univariate logistic regression analysis showed that M0 cytokines tended to be higher in good responders than in moderate responders.
Conclusion: Whereas TNF-inhibitor inhibits chemokine type cytokines and might reduce infiltration of inflammatory cells, TCZ inhibits T-cell-related cytokines and might normalize the immunological abnormality. Therefore, it is possible that TCZ can induce a deeper remission than TNF-inhibitors. In patients with high T-cell-related cytokine values before treatment, good response can be expected with TCZ.
|Difference between TCZ and TNF inhibitor in inhibition of cytokines|
|TCZ group||TNF-inhibitor group|
|Significant inhibition at M6||IL-2, IL-7, IL-8, IL-12, GM-CSF, TNF||IL-6, IL-8, MIP-1β, CCL-20|
|Among good responders, decrease to ≤40% at M6||IL-2, IL-7, IL-10, IL-12, GM-CSF, IFNγ||IL-6, IL-12, CCL-20|
|* IL-4, IL-5, IL-13, IL-17 and IL-23 were undetectable in more than 50% of RA patients at M0, so they were excluded from the analysis.|
Disclosure: J. Yamana, None; M. Iwahashi, None; M. Kim, None; R. Sasaki, None; K. Kobayashi, None; S. Yamana, None; Y. Sasaki, Chugai Pharmaceutical, 3 ; Y. Shimonaka, Chugai Pharmaceutical, 3 ; M. Mihara, Chugai Pharmaceutical, 3 .