Response to: ‘Comment on ‘Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: the RRRR study, a randomised controlled trial’ by Tanaka et al’ by Berkhout et al
Response to: ‘Comment on ‘Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: the RRRR study, a randomised controlled trial’ by Tanaka et al’ by Berkhout et al
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回应：Berkhout 等人对“类风湿关节炎患者获得缓解后持续停用英夫利昔单抗并增加剂量策略的评论：RRRR 研究，一项随机对照试验”，田中等人”，Berkhout 等人
DOI：
10.1136/annrheumdis-2019-216593
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发表时间：
2019
影响因子：
27.4
通讯作者：
Takeuchi Tsutomu
中科院分区：
文献类型：
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作者：
Tanaka Yoshiya;Oba Koji;Takeuchi Tsutomu
我们要感谢Berkhout等人在我们的论文中对血清TNF浓度与英夫利西单抗治疗反应之间不存在相关性的评论。1首先，由于评估血清的实验室公司对评估的质量控制进行了严格管理，因此应明确证实研究中获得的血清TNF水平结果的可靠性。然而，正如他们所提到的，目前尚不清楚任何细胞因子的血清水平如何反映其在炎症组织中产生的组织水平。在上下文中有一个限制。其次，如在线补充表1所示，在研究基线时血清TNF水平低、中和高的程序治疗组之间，英夫利西单抗的血清水平无差异。2在RISING研究中也看到了类似的结果。4然而，由于在一些患者中检测到抗药抗体（ADA），尽管数量非常有限，因此不能排除低浓度英夫利西单抗可能是ADA形成的结果的假设。第三，我们同意血清TNF水平可能不能充分反映炎症和疾病活动。研究的关键点是，根据政府批准的用法，我们在第14周之前不能递增剂量2，并且这可能会降低计划治疗策略的疗效，因为开始时间可能是通过微调剂量实现临床缓解的最重要时期。然而，最近在使用电化学发光和其他方法评估蛋白质方面的进展将保证血清蛋白水平估计的改进。否则，是否有任何替代标志物优于治疗达标所需的TNF而不是TNF本身？
We would like to thank Berkhout et al for their comments on the absence of an association between serum TNF concentrations and treatment response to infliximab in our paper. 1 First, reliability of the obtained results on the serum levels of TNF in the study should be firmly confirmed, because the quality control of the assessments was stringently managed by the laboratory company who assessed the serum. 2 3 However, as they mentioned, it remains unclear how serum levels of any cytokines reflect their tissue levels produced in inflamed tissues. There was a limitation in the context. Second, serum levels of infliximab did not differ among the programmed treatment groups with low, intermediate and high levels of serum TNF at the baseline in the study, as shown in the online supplementary table 1. 2 Similar results were also seen in the RISING study. 4 However, because antidrug antibodies (ADA) were detected in some patients though very limited number, the assumption that low concentration of infliximab might be results of ADA formation cannot be excluded. Third, we agree that serum levels of TNF may not adequately reflect inflammation and disease activity. The critical point of the study was that we could not escalate the dose until week 14 according to the approved usage by the government 2 and that it might reduce the efficacy of the programmed treatment strategy since the very start time may be the most important period to achieve a clinical remission by fine tuning the dose. However, recent progress in assessments of proteins using electrochemiluminescence and other methods would warrant improvement of the estimation of serum protein levels. Otherwise, are any surrogate markers better than TNF required for the treat-to-target instead of TNF itself?