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AB0581 The relationship between macrophage migration inhibitory factor and clinical responsiveness to tocilizumab in patients with rheumatoid arthritis
  1. T. Kasama,
  2. K. Ohtsuka,
  3. R. Yanai,
  4. H. Furuya,
  5. M. Sato,
  6. R. Takahashi,
  7. K. Wakabayashi,
  8. N. Yajima,
  9. Y. Miwa
  1. Division of Rheumatology, Showa University, Tokyo, Japan

Abstract

Background Chemokines are key mediators of the pathogenesis of rheumatoid arthritis (RA). Because tocilizumab,a humanized monoclonal antibody that is specific for the IL-6 receptor,induces rapid clinical improvement in RA patients, the clinical and serum factors that are correlated with the responsiveness to tocilizumab should be determined.

Objectives To examine the relationship between serum chemokine levels and clinical responsiveness to tocilizumab in patients with RA and to investigate the impact of tocilizumab administration on serum chemokine levels

Methods The disease status of 21 RA patientswas assessed at baseline and after 12 weeks of tocilizumab administration (8 mg/kg) using the clinical disease activity index (CDAI) and the disease activity score 28 (DAS28). The minor, moderate and major responses to tocilizumabwere defined as an improvement of greater than 50%, 70% and 85%, respectively, from the baseline CDAI, which is consistent with the improvement criteria proposed by Aletaha and Smolen et al.1Serum levels of the following chemokines at baseline and after 12 weeks were quantified using double ligand enzyme-linked immunosorbent assays: CCL2, CCL3, CXCL8, CXCL10, CX3CL1 and macrophage migration inhibitory factor (MIF).

Results At the initiation of therapy, the mean age of the patients was 56.1 yrs, the mean disease duration was 11.8 yrs, and the mean baseline CDAI was 22.4. After 12 weeks of tocilizumab administration, 14 patients achieved a greater than 50% improvement (referred to as the responder group), but there were no significant responses in the other 7 patients (the nonresponder group). No significant differences were found for disease activity (CDAI and DAS28), serum C-reactive protein levels, prior use of TNF antagonists between the groups. Although serum baseline levels of CCL2 and CXCL8 were higher in the responder group than in the nonresponder group, there were no significant changes in these chemokine levels after tocilizumab administration. In addition, the serum MIF levels at baseline were higher in the responder group than in the nonresponder group, although this difference was not statistically significant. Furthermore, the serum MIF levels in the responsive group, but not in the nonresponder group, were significantly decreased after tocilizumab administration (2225.8±1527.0 to 1038.7±981.4 pg/ml at week 12, p<0.05). A comparison between patients with lower basal MIF levels (median level of <1347 pg/ml) and higher basal MIF levels (≥1347 pg/ml) revealed no significant differences in patient characteristics. However, in response to tocilizumab, serum MIF levels decreased in patients with higher basal MIF levels (2875.5±1407.8 to 1189.7±1070.0, p<0.05) but not in those with lower basal levels.

Conclusions In this study, we found that tocilizumab had no significant effect on serum chemokine levels, excluding MIF levels, which were affected by TNF antagonists2. These results may support the hypothesis that the production of proinflammatory cytokines, and chemokines depends on TNF-α stimulation; however, only MIF may be dominantly regulated by the IL-6/IL-6 receptor system and may have a crucial role in the pathogenesis of RA.

  1. Aletaha D, et al. Arthritis Rheum 2011;63:S2226.

  2. Kasama T, et al. J Clin Rheumatol Musculoskel Med 2010;1:19.

Disclosure of Interest None Declared

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