Eun Sil Kim, Yiyoung Kwon, Yon Ho Choe, Mi Jin Kim
{"title":"对英夫利昔单抗的游离抗体是预测儿童克罗恩病继发性反应丧失患者剂量强化效果的生物标志物。","authors":"Eun Sil Kim, Yiyoung Kwon, Yon Ho Choe, Mi Jin Kim","doi":"10.1177/17562848231170948","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immunogenicity to antitumor necrosis factor alpha agents, such as infliximab (IFX), may lead to therapeutic failure.</p><p><strong>Objectives: </strong>This study evaluated the relationship between free and total antibodies-to-infliximab (ATIs), trough levels (TLs) of IFX, and the response to dose intensification.</p><p><strong>Design: </strong>We performed a prospective, observational study including pediatric patients with Crohn's disease (CD) receiving IFX maintenance therapy without dose intensification.</p><p><strong>Methods: </strong>We compared clinical and laboratory outcomes according to the presence of free and total ATIs. Factors associated with response to IFX dose intensification were investigated by analyzing IFX TLs and free and total ATIs.</p><p><strong>Results: </strong>Of the 98 patients, 9 patients had detectable free ATIs and 38 patients had total ATIs. Patients with free ATIs had significantly lower TLs (0.7 <i>versus</i> 5.1 µg/mL, <i>p</i> < 0.001) than patients without free ATIs. However, there was no difference in the IFX TLs according to the presence of total ATIs (<i>p</i> = 0.2523). Analysis of the 38 samples with total ATIs showed that response to dose intensification was significantly lower in patients with free ATIs than those without free ATIs (22.2% <i>versus</i> 65.5%, <i>p</i> < 0.001). In addition, free ATIs were the only factor with poor response to dose intensification [odds ratio (OR): 14.15, 95% confidence interval (CI): 1.31-151.97, <i>p</i> = 0.0140]. According to the receiver operating characteristic analysis, the optimal cutoff level indicating non-response to IFX dose intensification was 30.0 AU/mL for free ATIs concentration (area under curve, 0.792; 95% CI: 0.590-0.942; sensitivity, 60.0%; specificity, 96.7%; <i>p</i> = 0.0241).</p><p><strong>Conclusion: </strong>Free ATIs, but not total ATIs, have a negative impact on the course of CD. Free ATIs are potential reliable biomarker for predicting the effect of dose intensification in patients with loss of response to IFX. Future studies based on serial and proactive therapeutic drug monitoring are required in the future.</p>","PeriodicalId":23022,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/77/9e/10.1177_17562848231170948.PMC10164862.pdf","citationCount":"0","resultStr":"{\"title\":\"Free antibodies-to-infliximab are biomarker for predicting the effect of dose intensification in pediatric Crohn's disease patients with secondary loss of response.\",\"authors\":\"Eun Sil Kim, Yiyoung Kwon, Yon Ho Choe, Mi Jin Kim\",\"doi\":\"10.1177/17562848231170948\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Immunogenicity to antitumor necrosis factor alpha agents, such as infliximab (IFX), may lead to therapeutic failure.</p><p><strong>Objectives: </strong>This study evaluated the relationship between free and total antibodies-to-infliximab (ATIs), trough levels (TLs) of IFX, and the response to dose intensification.</p><p><strong>Design: </strong>We performed a prospective, observational study including pediatric patients with Crohn's disease (CD) receiving IFX maintenance therapy without dose intensification.</p><p><strong>Methods: </strong>We compared clinical and laboratory outcomes according to the presence of free and total ATIs. Factors associated with response to IFX dose intensification were investigated by analyzing IFX TLs and free and total ATIs.</p><p><strong>Results: </strong>Of the 98 patients, 9 patients had detectable free ATIs and 38 patients had total ATIs. Patients with free ATIs had significantly lower TLs (0.7 <i>versus</i> 5.1 µg/mL, <i>p</i> < 0.001) than patients without free ATIs. However, there was no difference in the IFX TLs according to the presence of total ATIs (<i>p</i> = 0.2523). Analysis of the 38 samples with total ATIs showed that response to dose intensification was significantly lower in patients with free ATIs than those without free ATIs (22.2% <i>versus</i> 65.5%, <i>p</i> < 0.001). In addition, free ATIs were the only factor with poor response to dose intensification [odds ratio (OR): 14.15, 95% confidence interval (CI): 1.31-151.97, <i>p</i> = 0.0140]. According to the receiver operating characteristic analysis, the optimal cutoff level indicating non-response to IFX dose intensification was 30.0 AU/mL for free ATIs concentration (area under curve, 0.792; 95% CI: 0.590-0.942; sensitivity, 60.0%; specificity, 96.7%; <i>p</i> = 0.0241).</p><p><strong>Conclusion: </strong>Free ATIs, but not total ATIs, have a negative impact on the course of CD. Free ATIs are potential reliable biomarker for predicting the effect of dose intensification in patients with loss of response to IFX. 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引用次数: 0
摘要
背景:抗肿瘤坏死因子α药物的免疫原性，如英夫利昔单抗(IFX)，可能导致治疗失败。目的:本研究评估IFX的游离抗体和总抗体(ATIs)、谷水平(TLs)与剂量强化反应的关系。设计:我们进行了一项前瞻性观察性研究，包括克罗恩病(CD)的儿科患者接受IFX维持治疗而不增加剂量。方法:根据游离ATIs和总ATIs的存在情况，比较临床和实验室结果。通过分析IFX的TLs、游离ATIs和总ATIs，探讨与IFX剂量增强反应相关的因素。结果:98例患者中，可检出游离ATIs 9例，总ATIs 38例。游离ATIs患者的TLs显著降低(0.7 vs 5.1µg/mL, p p = 0.2523)。对38例总ATIs患者的分析显示，游离ATIs患者对剂量强化的反应明显低于无游离ATIs患者(22.2% vs 65.5%， p p = 0.0140)。根据受试者工作特征分析，游离ATIs浓度为30.0 AU/mL(曲线下面积0.792;95% ci: 0.590-0.942;敏感性,60.0%;特异性,96.7%;p = 0.0241)。结论:游离ATIs，而非总ATIs，对CD病程有负面影响。游离ATIs是预测对IFX失去反应的患者剂量强化效果的潜在可靠的生物标志物。未来的研究需要基于连续和主动的治疗药物监测。
Free antibodies-to-infliximab are biomarker for predicting the effect of dose intensification in pediatric Crohn's disease patients with secondary loss of response.
Background: Immunogenicity to antitumor necrosis factor alpha agents, such as infliximab (IFX), may lead to therapeutic failure.
Objectives: This study evaluated the relationship between free and total antibodies-to-infliximab (ATIs), trough levels (TLs) of IFX, and the response to dose intensification.
Design: We performed a prospective, observational study including pediatric patients with Crohn's disease (CD) receiving IFX maintenance therapy without dose intensification.
Methods: We compared clinical and laboratory outcomes according to the presence of free and total ATIs. Factors associated with response to IFX dose intensification were investigated by analyzing IFX TLs and free and total ATIs.
Results: Of the 98 patients, 9 patients had detectable free ATIs and 38 patients had total ATIs. Patients with free ATIs had significantly lower TLs (0.7 versus 5.1 µg/mL, p < 0.001) than patients without free ATIs. However, there was no difference in the IFX TLs according to the presence of total ATIs (p = 0.2523). Analysis of the 38 samples with total ATIs showed that response to dose intensification was significantly lower in patients with free ATIs than those without free ATIs (22.2% versus 65.5%, p < 0.001). In addition, free ATIs were the only factor with poor response to dose intensification [odds ratio (OR): 14.15, 95% confidence interval (CI): 1.31-151.97, p = 0.0140]. According to the receiver operating characteristic analysis, the optimal cutoff level indicating non-response to IFX dose intensification was 30.0 AU/mL for free ATIs concentration (area under curve, 0.792; 95% CI: 0.590-0.942; sensitivity, 60.0%; specificity, 96.7%; p = 0.0241).
Conclusion: Free ATIs, but not total ATIs, have a negative impact on the course of CD. Free ATIs are potential reliable biomarker for predicting the effect of dose intensification in patients with loss of response to IFX. Future studies based on serial and proactive therapeutic drug monitoring are required in the future.
期刊介绍：
Therapeutic Advances in Gastroenterology is an open access journal which delivers the highest quality peer-reviewed original research articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of gastrointestinal and hepatic disorders. The journal has a strong clinical and pharmacological focus and is aimed at an international audience of clinicians and researchers in gastroenterology and related disciplines, providing an online forum for rapid dissemination of recent research and perspectives in this area.
The editors welcome original research articles across all areas of gastroenterology and hepatology.
The journal publishes original research articles and review articles primarily. Original research manuscripts may include laboratory, animal or human/clinical studies – all phases. Letters to the Editor and Case Reports will also be considered.
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