Serum TNFα levels at 24 h after certolizumab pegol predict effectiveness at week 12 in patients with rheumatoid arthritis from TSUBAME study.

OBJECTIVE: To estimate the relationship between serum TNFα, IL-6, and serum CZP levels and the clinical response to CZP in RA patients in the TSUBAME study. METHODS: One hundred patients with RA who received CZP were enrolled and multiple clinical parameters, serum TNFα, IL-6, and CZP levels, were assessed at 0, 24, and 48 h and 12 weeks after first administration of CZP. RESULTS: The CZP therapy significantly improved the DAS28(ESR) at 12 weeks. Serum TNFα and IL-6 levels significantly decreased from baseline at 24 h after the first administration of CZP. Serum TNFα levels at baseline were not related to clinical parameters at baseline and improvement in DAS28(ESR) at week 12 of the CZP therapy. However, serum levels of CZP at 24 h were strongly and negatively correlated with TNFα levels at 24 h, which were negatively correlated with improved rate in DAS28(ESR) at week 12. Only serum levels of TNFα, but not IL-6, at 24 h had a negative correlation with achievement of DAS28(ESR)<2.6 at week 12 by the multivariate analysis (odds ratio 0.01, 95% confidence interval 0.04e-2-0.22, p < 0.01). A receiver operating characteristic analysis was conducted to estimate the achievement of DAS28(ESR)<2.6 at week 12 after the CZP therapy and cut-off value of 0.76 pg/ml for serum levels of TNFα at 24 h was yielded (area under the curve=0.75). DAS28(ESR)<2.6 was achieved at week 12 significantly more patients with lower serum TNF levels (≦0.76 pg/ml) at 24 h than those with higher TNF levels. CONCLUSIONS: CZP was highly effective in RA patients who had low serum TNFα levels at 24 h after the initial administration of CZP. Therefore, we propose that serum TNFα levels at 24 h could serve as a biomarker predicting effectiveness to CZP at week 12 in patients with RA. TRIAL REGISTRATION: Clinical trial registration number: UMIN ID:000022831.