José Luis Rueda García, Cristina Suárez-Ferrer, Clara Amiama Roig, Laura García Ramírez, Cristina García Rojas, Eduardo Martín-Arranz, Joaquín Poza Cordón, María Sánchez Azofra, Jesús Noci, Cristina Cubillo García, María Dolores Martín-Arranz
{"title":"阿达木单抗早期治疗药物监测与克罗恩病生物缓解和药物生存的关系","authors":"José Luis Rueda García, Cristina Suárez-Ferrer, Clara Amiama Roig, Laura García Ramírez, Cristina García Rojas, Eduardo Martín-Arranz, Joaquín Poza Cordón, María Sánchez Azofra, Jesús Noci, Cristina Cubillo García, María Dolores Martín-Arranz","doi":"10.1177/17562848251324226","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Therapeutic drug monitoring of adalimumab (ADA) is still controversial.</p><p><strong>Objectives: </strong>To study the association between ADA trough levels in the early stages of treatment with biological remission (BR) and drug survival in Crohn's disease (CD).</p><p><strong>Design: </strong>Retrospective cohort study.</p><p><strong>Methods: </strong>Patients treated with ADA with available trough levels at weeks 2 and 6 (after the first induction and maintenance dose, respectively) were included. Fecal calprotectin (Fcal) and C-reactive protein (CRP) were registered at baseline, week 24, and week 52. BR was defined as Fcal <200 µg/g and CRP <5 mg/dl. Treatment survival and the need for dose escalation were assessed at week 52. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of ADA cutoff levels for BR. Quartile-specific comparisons were performed to evaluate differences in the proportion of patients achieving BR at weeks 24 and 52, drug survival, and dose escalation.</p><p><strong>Results: </strong>In all, 112 patients were included. ADA trough levels at week 6 were higher in patients achieving BR at week 24 (12.32 μg/ml vs 10.3 μg/ml, <i>p</i> = 0.0008), week 52 (12.3 μg/ml vs 10.8 μg/ml, <i>p</i> = 0.035), and in patients with 1-year treatment persistence (12.17 μg/ml vs 9.7 μg/ml, <i>p</i> = 0.03), but lower in patients requiring maintenance intensification (9.7 μg/ml vs 12.2 µg/ml, <i>p</i> < 0.0001). ADA week 6 trough levels >12.27 μg/ml predicted BR at week 24 with 79.7% specificity and 79.5% positive predictive value. Patients in the third quartile (Q3) and fourth quartile (Q4) of ADA levels at week 6 exhibited higher rates of BR at week 24, BR at week 52, 1-year drug survival, and less need for dose escalation (all <i>p</i>-values <0.05). In logistic regression, Q3 and Q4 of week 6 levels were significantly associated with BR at week 24 (<i>p</i> = 0.02 and <i>p</i> = 0.001); and week 6 Q4 with BR at week 52 (<i>p</i> = 0.02), treatment persistence (<i>p</i> = 0.03), and lower dose escalation (<i>p</i> = 0.004). ADA trough levels at week 2 did not show similar associations.</p><p><strong>Conclusion: </strong>ADA trough levels at week 6 are associated with BR at weeks 24 and 52, drug survival, and need for dose escalation in CD. However, ADA concentrations at week 2 failed to yield similar results.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":"18 ","pages":"17562848251324226"},"PeriodicalIF":3.9000,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921000/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association of early therapeutic drug monitoring of adalimumab with biologic remission and drug survival in Crohn's Disease.\",\"authors\":\"José Luis Rueda García, Cristina Suárez-Ferrer, Clara Amiama Roig, Laura García Ramírez, Cristina García Rojas, Eduardo Martín-Arranz, Joaquín Poza Cordón, María Sánchez Azofra, Jesús Noci, Cristina Cubillo García, María Dolores Martín-Arranz\",\"doi\":\"10.1177/17562848251324226\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Therapeutic drug monitoring of adalimumab (ADA) is still controversial.</p><p><strong>Objectives: </strong>To study the association between ADA trough levels in the early stages of treatment with biological remission (BR) and drug survival in Crohn's disease (CD).</p><p><strong>Design: </strong>Retrospective cohort study.</p><p><strong>Methods: </strong>Patients treated with ADA with available trough levels at weeks 2 and 6 (after the first induction and maintenance dose, respectively) were included. Fecal calprotectin (Fcal) and C-reactive protein (CRP) were registered at baseline, week 24, and week 52. BR was defined as Fcal <200 µg/g and CRP <5 mg/dl. Treatment survival and the need for dose escalation were assessed at week 52. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of ADA cutoff levels for BR. Quartile-specific comparisons were performed to evaluate differences in the proportion of patients achieving BR at weeks 24 and 52, drug survival, and dose escalation.</p><p><strong>Results: </strong>In all, 112 patients were included. ADA trough levels at week 6 were higher in patients achieving BR at week 24 (12.32 μg/ml vs 10.3 μg/ml, <i>p</i> = 0.0008), week 52 (12.3 μg/ml vs 10.8 μg/ml, <i>p</i> = 0.035), and in patients with 1-year treatment persistence (12.17 μg/ml vs 9.7 μg/ml, <i>p</i> = 0.03), but lower in patients requiring maintenance intensification (9.7 μg/ml vs 12.2 µg/ml, <i>p</i> < 0.0001). ADA week 6 trough levels >12.27 μg/ml predicted BR at week 24 with 79.7% specificity and 79.5% positive predictive value. Patients in the third quartile (Q3) and fourth quartile (Q4) of ADA levels at week 6 exhibited higher rates of BR at week 24, BR at week 52, 1-year drug survival, and less need for dose escalation (all <i>p</i>-values <0.05). In logistic regression, Q3 and Q4 of week 6 levels were significantly associated with BR at week 24 (<i>p</i> = 0.02 and <i>p</i> = 0.001); and week 6 Q4 with BR at week 52 (<i>p</i> = 0.02), treatment persistence (<i>p</i> = 0.03), and lower dose escalation (<i>p</i> = 0.004). ADA trough levels at week 2 did not show similar associations.</p><p><strong>Conclusion: </strong>ADA trough levels at week 6 are associated with BR at weeks 24 and 52, drug survival, and need for dose escalation in CD. However, ADA concentrations at week 2 failed to yield similar results.</p>\",\"PeriodicalId\":48770,\"journal\":{\"name\":\"Therapeutic Advances in Gastroenterology\",\"volume\":\"18 \",\"pages\":\"17562848251324226\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-03-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921000/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Gastroenterology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17562848251324226\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17562848251324226","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：阿达木单抗（ADA）的治疗药物监测仍存在争议。目的：研究克罗恩病（Crohn’s disease， CD）生物缓解（BR）治疗早期ADA谷底水平与药物生存期的关系。设计：回顾性队列研究。方法：纳入在第2周和第6周（分别在第一次诱导和维持剂量后）具有可用谷水平的ADA治疗患者。在基线、第24周和第52周记录粪便钙保护蛋白（Fcal）和c反应蛋白（CRP）。BR定义为Fcal结果：总共纳入112例患者。第6周ADA谷水平在第24周达到BR的患者（12.32 μg/ml vs 10.3 μg/ml, p = 0.0008）、第52周（12.3 μg/ml vs 10.8 μg/ml, p = 0.035）和持续治疗1年的患者（12.17 μg/ml vs 9.7 μg/ml, p = 0.03）中较高，但在需要维持强化的患者中较低(9.7 μg/ml vs 12.2 μg/ml, p 12.27 μg/ml预测第24周BR，特异性为79.7%，阳性预测值为79.5%。第6周ADA水平的第三四分位数（Q3）和第四四分位数（Q4）患者在第24周和第52周表现出更高的BR率，1年药物生存期，更少需要增加剂量（所有p值p = 0.02和p = 0.001）；第6周Q4，第52周BR （p = 0.02）、治疗持续（p = 0.03）和较低剂量递增（p = 0.004）。第2周的ADA低谷水平没有显示出类似的关联。结论：第6周的ADA谷底水平与第24周和第52周的BR、药物生存期和CD的剂量增加需求相关。然而，第2周的ADA浓度未能产生类似的结果。
Association of early therapeutic drug monitoring of adalimumab with biologic remission and drug survival in Crohn's Disease.
Background: Therapeutic drug monitoring of adalimumab (ADA) is still controversial.
Objectives: To study the association between ADA trough levels in the early stages of treatment with biological remission (BR) and drug survival in Crohn's disease (CD).
Design: Retrospective cohort study.
Methods: Patients treated with ADA with available trough levels at weeks 2 and 6 (after the first induction and maintenance dose, respectively) were included. Fecal calprotectin (Fcal) and C-reactive protein (CRP) were registered at baseline, week 24, and week 52. BR was defined as Fcal <200 µg/g and CRP <5 mg/dl. Treatment survival and the need for dose escalation were assessed at week 52. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of ADA cutoff levels for BR. Quartile-specific comparisons were performed to evaluate differences in the proportion of patients achieving BR at weeks 24 and 52, drug survival, and dose escalation.
Results: In all, 112 patients were included. ADA trough levels at week 6 were higher in patients achieving BR at week 24 (12.32 μg/ml vs 10.3 μg/ml, p = 0.0008), week 52 (12.3 μg/ml vs 10.8 μg/ml, p = 0.035), and in patients with 1-year treatment persistence (12.17 μg/ml vs 9.7 μg/ml, p = 0.03), but lower in patients requiring maintenance intensification (9.7 μg/ml vs 12.2 µg/ml, p < 0.0001). ADA week 6 trough levels >12.27 μg/ml predicted BR at week 24 with 79.7% specificity and 79.5% positive predictive value. Patients in the third quartile (Q3) and fourth quartile (Q4) of ADA levels at week 6 exhibited higher rates of BR at week 24, BR at week 52, 1-year drug survival, and less need for dose escalation (all p-values <0.05). In logistic regression, Q3 and Q4 of week 6 levels were significantly associated with BR at week 24 (p = 0.02 and p = 0.001); and week 6 Q4 with BR at week 52 (p = 0.02), treatment persistence (p = 0.03), and lower dose escalation (p = 0.004). ADA trough levels at week 2 did not show similar associations.
Conclusion: ADA trough levels at week 6 are associated with BR at weeks 24 and 52, drug survival, and need for dose escalation in CD. However, ADA concentrations at week 2 failed to yield similar results.
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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