针对英夫利昔单抗或阿达木单抗的抗体存在与否决定转用依那西普的疗效

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Ann Rheum Dis 2011;70:284-288 doi:10.1136/ard.2010.135111 The presence or absence of antibodies to infliximab or adalimumab determines the outcome of switching to etanercept 1.       Anna Jamnitski1, 2.       Geertje M Bartelds1, 3.       Michael T Nurmohamed1,2, 4.       Pauline A van Schouwenburg3, 5.       Dirkjan van Schaardenburg1,2, 6.       Steven O Stapel3, 7.       Ben A C Dijkmans1,2, 8.       Lucien Aarden3, 9.       Gerrit Jan Wolbink1,3 + Author Affiliations 1.       1Jan van Breemen Institute, Amsterdam, The Netherlands 2.       2VU University Medical Centre, Amsterdam, The Netherlands 3.       3Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands Abstract Objective 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. Methods 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). Results 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). Conclusion 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.

针对英夫利昔单抗或阿达木单抗的抗体存在与否决定转用依那西普的疗效 Jamnitski A, et al. Ann Rheum Dis. 2011;70:284-288.   目的：本研究旨在探讨第一种TNF抑制剂无效的原因（免疫原性或其他原因）是否决定第二种TNF抑制剂的疗效。   方法：该队列研究共纳入292例RA患者，均使用依那西普。其中，89例（30%）之前使用英夫利昔单抗或阿达木单抗（转换者），其余203例（70%）为初次使用TNF抑制剂。转换者根据是否存在针对之前生物制剂的抗体分为两组。治疗28周后，根据DAS28，比较依那西普在转换者（有或无抗体）和初次使用者中的疗效。   结果：治疗28周后，初次使用者和存在抗体的转换者之间疗效没有差别（ΔDAS28=2.1±1.3 vs ΔDAS28=2.0±1.3; p=0.743）。与初次使用者（ΔDAS28=1.2±1.3 vs ΔDAS28=2.1±1.3; p=0.001）和存在抗体的转换者（ΔDAS28=1.2±1.3 vs ΔDAS28=2.0±1.3; p=0.017）相比，没有抗体的转换者疗效较差。   结论：与没有抗药物抗体的RA患者相比，对第一种TNF抑制剂有免疫原性反应的RA患者使用其他TNF抑制剂疗效更好。因此，明确免疫原性有助于确定哪些患者转换药物后疗效更佳，可将其作为个体化治疗的一部分。