Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.
Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.
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DOI：
10.1111/apt.17170
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发表时间：
2022-10
影响因子：
7.6
通讯作者：
Ahmad, Tariq
中科院分区：
文献类型：
--
作者：
Chanchlani, Neil;Lin, Simeng;Auth, Marcus K.;Lee, Chai Leng;Robbins, Helena;Looi, Shi;Murugesan, Senthil, V;Riley, Tom;Preston, Cathryn;Stephenson, Sophie;Cardozo, Wendy;Sonwalkar, Sunil A.;Allah-Ditta, Mohammed;Mansfield, Lynne;Durai, Dharmaraj;Baker, Mark;London, Ian;London, Emily;Gupta, Sanjay;Di Mambro, Alex;Murphy, Aisling;Gaynor, Edward;Jones, Kelsey D. J.;Claridge, Andrew;Sebastian, Shaji;Ramachandran, Sankaranarayanan;Selinger, Christian P.;Borg-Bartolo, Simon P.;Knight, Paul;Sprakes, Michael B.;Burton, Julie;Kane, Patricia;Lupton, Stephanie;Fletcher, Aimee;Gaya, Daniel R.;Colbert, Roghan;Seenan, John Paul;MacDonald, Jonathan;Lynch, Lucy;McLachlan, Iain;Shields, Stephanie;Hansen, Richard;Gervais, Lisa;Jere, Mwansa;Akhtar, Muhammad;Black, Karen;Henderson, Paul;Russell, Richard K.;Lees, Charlie W.;Derikx, Lauranne A. A. P.;Lockett, Melanie;Betteridge, Frederica;De Silva, Aminda;Hussenbux, Arif;Beckly, John;Bendall, Oliver;Hart, James W.;Thomas, Amanda;Hamilton, Ben;Gordon, Claire;Chee, Desmond;McDonald, Timothy J.;Nice, Rachel;Parkinson, Marian;Gardner-Thorpe, Helen;Butterworth, Jeff R.;Javed, Asima;Al-Shakhshir, Sarah;Yadagiri, Rekha;Maher, Sebrene;Pollok, Richard C. G.;Ng, Tze;Appiahene, Priscilla;Donovan, Fiona;Lok, James;Chandy, Rajiv;Jagdish, Reema;Baig, Daniyal;Mahmood, Zahid;Marsh, Liane;Moss, Allison;Abdulgader, Amin;Kitchin, Angus;Walker, Gareth J.;George, Becky;Lim, Yuen-Hui;Gulliver, James;Bloom, Stuart;Theaker, Holly;Carlson, Sean;Cummings, J. R. Fraser;Livingstone, Robert;Beale, Amanda;Carter, Josiah O.;Bell, Andrew;Coulter, Archibald;Snook, Jonathon;Stone, Helen;Kennedy, Nicholas A.;Goodhand, James R.;Ahmad, Tariq
在炎症性肠病（IBD）患者中，抗药抗体与抗TNF药物治疗失败相关。为了评估患者第一种抗TNF药物的免疫原性是否与第二种抗TNF药物的免疫原性相关，无论药物序列如何，我们进行了一项英国范围内的多中心回顾性队列研究，以报告1058例接受英夫利西单抗和阿达木单抗治疗药物监测的IBD患者中第二种抗TNF治疗的免疫原性和治疗失败率。主要结局为第二种抗TNF药物的免疫原性，定义为任何时间点英夫利西单抗的抗TNF抗体浓度≥9 Au/ml，阿达木单抗的抗TNF抗体浓度≥6 Au/ml。在接受英夫利西单抗和阿达木单抗治疗的患者中，与未出现英夫利西单抗抗体的患者相比，出现英夫利西单抗抗体的患者更可能出现阿达木单抗抗体（OR 1.99，95%CI 1.27-3.20，p = 0.002）。同样，在先接受阿达木单抗治疗，然后接受英夫利西单抗治疗的患者中，阿达木单抗的免疫原性与随后接受英夫利西单抗的免疫原性相关（OR 2.63，95%CI 1.46-4.80，p < 0.001）。抗英夫利昔单抗和抗阿达木单抗抗体浓度每增加10倍，随后产生阿达木单抗和英夫利昔单抗抗体的几率分别增加1.73（95%CI 1.38-2.17，p < 0.001）和1.99（95%CI 1.34-2.99，p < 0.001）。对英夫利西单抗产生免疫原性且药物水平不可检测的患者更可能对阿达木单抗产生免疫原性且药物水平不可检测（OR 2.37，95% CI 1.39-4.19，p < 0.001）。在转换为第二种抗TNF时开始使用免疫调节剂与免疫原性失败患者的药物持久性改善相关，但与药效学失败无关。无论药物顺序如何，对第一种抗TNF药物的免疫原性与对第二种药物的免疫原性相关，在免疫原性但非药效学治疗失败的患者中引入免疫调节剂可缓解这种免疫原性。在接受英夫利西单抗和阿达木单抗治疗药物监测的1058例炎症性肠病患者中，产生第一种抗TNF抗体的患者更有可能产生第二种抗TNF抗体，无论药物顺序如何。在转换为第二种抗TNF治疗时开始使用免疫调节剂与免疫原性但非药效学失败患者的药物持久性改善相关。
Anti‐drug antibodies are associated with treatment failure to anti‐TNF agents in patients with inflammatory bowel disease (IBD). To assess whether immunogenicity to a patient's first anti‐TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence We conducted a UK‐wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti‐TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti‐TNF agent, defined at any timepoint as an anti‐TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27–3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46–4.80, p < 0.001). For each 10‐fold increase in anti‐infliximab and anti‐adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38–2.17, p < 0.001) and 1.99 (95%CI 1.34–2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39–4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti‐TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. Irrespective of drug sequence, immunogenicity to the first anti‐TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure. In 1058 patients with inflammatory bowel disease who underwent therapeutic drug monitoring for both infliximab and adalimumab, those who developed antibodies to a first anti‐TNF were more likely to develop antibodies to a second anti‐TNF, irrespective of drug sequence. Commencing an immunomodulator at the time of switching to the second anti‐TNF was associated with improved drug persistence in patients with immunogenic but not pharmacodynamic failure.
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影响因子：
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作者：
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