Background Tocilizumab (TCZ), a humanized anti-IL-6 receptor (IL-6R) monoclonal antibody, specifically inhibits IL-6 activity by competitively binding to soluble (sIL-6R) and membrane-bound IL-6R. As for infliximab, a chimeric anti-TNF-α monoclonal antibody, baseline soluble TNF-α level is associated with the clinical response to infliximab in patients with rheumatoid arthritis (RA) 1.
Objectives The aim of this study was to investigate a possible role of baseline serum sIL-6R level on clinical effectiveness to TCZ in RA patients.
Methods Consecutive RA patients at our institution who received 8mg/kg of TCZ every 4 weeks between March 2010 and April 2012 after giving a written informed consent were included in this study. The serum level of sIL-6R was measured by electrochemiluminescence assay at baseline. The effects of baseline sIL-6R level on DAS28-ESR value and the rate of clinical remission (DAS28-ESR <2.6) at week 24 were examined.
Results Fifty-one patients were enrolled in this study. Median age of the patients was 60 years and median RA duration was 4.5 years. Median DAS28-ESR decreased from 5.11 at baseline to 1.95 at week 24, resulting in the achievement of DAS28-ESR <2.6 in 34 (67%) patients. Median (IQR) sIL-6R at baseline was 1556 (1179-1933) pg/ml. The value of sIL-6R was not correlated with age, disease duration, or DAS28-ESR at baseline. However, baseline sIL-6R level was significantly associated with DAS28-ESR at week 24 (rho=0.37, p<0.01; Figure). Logistic regression analysis revealed that baseline sIL-6R level was a significant predictor for DAS28-ESR remission at week 24 (p<0.01). Cut-off sIL-6R level of 1556 pg/ml discriminated remission from non-remission at a sensitivity of 82% and specificity of 65% (AUC=0.69), and the odds ratio was 6.0 (95%CI: 1.6-22.4). Moreover, 85% of the patients with sIL-6R level < 1556 pg/ml achieved remission, while only 48% in the other patients (p<0.01 by Fisher exact test).
Conclusions Baseline sIL-6R level is a predictive factor of clinical response to TCZ at week 24 in patients with RA. These results suggest that, as is the case with infliximab, the dosing regimen of TCZ could be adjusted by the amount of the molecular target to be neutralized.
Takeuchi T, et al. Ann Rheum Dis 2011;70:1208
Disclosure of Interest N. Nishina: None Declared, J. Kikuchi Consultant for: Pfizer Japan Inc., M. Hashizume Employee of: Chugai Pharmaceutical Co., Ltd., K. Yoshimoto: None Declared, H. Kameda: None Declared, T. Takeuchi Grant/research support from: Abbott Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Nippon Shinyaku Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical Co., Ltd.