Serum TNF\u03b1 levels at 24 h after certolizumab pegol predict effectiveness at week 12 in patients with rheumatoid arthritis from TSUBAME study

Yusuke Miyazaki,Shigeru Iwata,Ippei Miyagawa,Ayako Yamaguchi,Kazuhisa Nakano,Satoshi Kubo,Yoshiya Tanaka,Shunsuke Fukuyo,Shingo Nakayamada,Kazuyoshi Saito,Kentaro Hanami,Akio Kawabe

doi:10.1186/s13075-021-02547-2

Yusuke Miyazaki, Shigeru Iwata + Show 10 more

Open Access

https://doi.org/10.1186/s13075-021-02547-2

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Abstract

ObjectiveTo 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.MethodsOne 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.ResultsThe 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.ConclusionsCZP 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 registrationClinical trial registration number: UMIN ID:000022831

Highlights

Rheumatoid arthritis (RA) is a systemic inflammatory disease causing progressive joint destruction and irreversible functional impairmen t[1,2,3]
The inclusion criteria were in accordance with the Guideline for the use of TNF inhibitors in rheumatoid arthritis (RA) (2014 revised version) as follows; RA patients with residual high disease activity despite adequate use of MTX or MTX in combination with other biological drugs, patients with progressive bone erosion observed using Xray, or patients with DAS28-Erythrocyte sedimentation rate (ESR) ≥ 3.2 using MTX were included in the study
Certolizumab pegol (CZP) was previously shown to be more effective than placebo at 1 week after the first dose was administered [11, 12], and in this study, we found that simple disease activity index decreased 24 h after administration of the first dose

Summary

Introduction

Rheumatoid arthritis (RA) is a systemic inflammatory disease causing progressive joint destruction and irreversible functional impairmen t[1,2,3]. TNFα inhibitors suppress arthritis and bone destruction caused by RA and markedly improve RA prognosi s[5, 6]. In RA patients, early diagnosis and prompt initiation of intensive treatment can improve disease activity early, leading to inhibition of joint destructio n[8, 9]. A fast-acting drug that can achieve earlier remission is a superior treatment for RA. A high blood concentration of CZP can be rapidly achieved using a loading dose, which can be maintained by subcutaneous injection administered every 2 week s[10]

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