Jan van Breemen Institute, Amsterdam, The Netherlands.
Ann Rheum Dis. 2011 Feb;70(2):284-8. doi: 10.1136/ard.2010.135111. Epub 2010 Nov 10.
The aim of this study was to test the hypothesis that the reason for non-response (caused by immunogenicity or not) to a first tumour necrosis factor (TNF) inhibitor defines whether a second TNF inhibitor will be effective.
This cohort study consisted of 292 consecutive patients with rheumatoid arthritis (RA), all treated with etanercept. A total of 89 patients (30%) were treated previously with infliximab or adalimumab ('switchers'), and the remaining 203 (70%) were anti-TNF naive. All switchers were divided into two groups: with and without antibodies against the previous biological. Differences in clinical response to etanercept between switchers with and without antibodies and patients who were anti-TNF naive were assessed after 28 weeks of treatment using changes in Disease Activity Score in 28 joints (DAS28).
After 28 weeks of treatment, response to etanercept did not differ between patients who were anti-TNF naive and switchers with anti-drug antibodies (ΔDAS28=2.1 ± 1.3 vs ΔDAS28=2.0 ± 1.3; p = 0.743). In contrast, switchers without anti-drug antibodies had a diminished response to etanercept treatment compared to patients who were TNF naive (ΔDAS28 =1.2±1.3 vs ΔDAS28 = 2.1 ± 1.3; p = 0.001) and switchers with antibodies (ΔDAS28 =1.2±1.3 vs ΔDAS28 = 2.0 ± 1.3; p = 0.017).
Patients with RA with an immunogenic response against a first TNF-blocking agent had a better clinical response to a subsequent TNF blocker compared to patients with RA without anti-drug antibodies. Hence, determining immunogenicity can be helpful in deciding in which patient switching could be beneficial and can be part of a personalised treatment regimen.
本研究旨在验证这样一个假设,即对首次肿瘤坏死因子(TNF)抑制剂的无应答(是否由免疫原性引起)的原因决定了第二次 TNF 抑制剂是否有效。
本队列研究纳入了 292 例连续的类风湿关节炎(RA)患者,所有患者均接受依那西普治疗。共有 89 例(30%)患者之前接受过英夫利昔单抗或阿达木单抗(“转换者”)治疗,其余 203 例(70%)为首次接受 TNF 抑制剂治疗的患者。所有转换者分为两组:有和无先前生物制剂的抗体。在接受依那西普治疗 28 周后,通过 28 关节疾病活动度评分(DAS28)的变化评估有和无针对先前药物的抗体的转换者与首次接受 TNF 抑制剂治疗的患者之间对依那西普的临床反应差异。
在接受依那西普治疗 28 周后,首次接受 TNF 抑制剂治疗的患者与有针对药物抗体的转换者之间对依那西普的反应无差异(ΔDAS28=2.1±1.3 对 ΔDAS28=2.0±1.3;p=0.743)。相比之下,无针对药物抗体的转换者对依那西普治疗的反应明显低于首次接受 TNF 抑制剂治疗的患者(ΔDAS28=1.2±1.3 对 ΔDAS28=2.1±1.3;p=0.001)和有针对药物抗体的转换者(ΔDAS28=1.2±1.3 对 ΔDAS28=2.0±1.3;p=0.017)。
与无针对药物抗体的 RA 患者相比,对首次 TNF 阻断剂产生免疫反应的 RA 患者对随后的 TNF 阻滞剂有更好的临床反应。因此,确定免疫原性有助于确定在哪些患者中转换可能有益,并且可以成为个体化治疗方案的一部分。