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IBD
Long-term clinical and real-world experience with Crohn’s disease treated with anti-tumor necrosis factor-α antibodies
Haruka Otake, Satohiro Matsumoto, Hirosato Mashima
Intest Res 2022;20(4):464-474.   Published online March 31, 2022
DOI: https://doi.org/10.5217/ir.2021.00139
AbstractAbstract PDFPubReaderePub
Background/Aims
Although anti-tumor necrosis factor (TNF)-α agents are important therapeutic drugs for Crohn’s disease (CD), data regarding their long-term sustained effects are limited. Herein, we evaluated the long-term loss of response (LOR) to anti-TNF-α agents in patients with CD.
Methods
This retrospective study included patients with CD who started treatment with infliximab or adalimumab as a first-line therapeutic approach. The cumulative event-free, retention, and surgery-free rates after the start of biological therapy were analyzed. Secondary LOR was analyzed in patients who achieved corticosteroid-free clinical remission after the start of biological therapy. Cox proportional hazards models were used to analyze the predictive factors of secondary LOR.
Results
The cumulative event-free rates at 1, 2, 5, and 10 years were 83.3%, 75.1%, 37.4%, and 23.3%, respectively. The incidence of LOR was 10.6% per patient-year of follow-up. At 12–14 weeks after the start of biological therapy, the proportion of patients with a C-reactive protein to albumin (CRP/ALB) ratio ≥0.18 was significantly higher in patients with LOR (P<0.001). Multivariate analysis indicates that a CRP/ALB ratio ≥0.18 (hazard ratio [HR], 5.86; 95% confidence interval [CI], 1.56–22.0; P=0.009) and upper gastrointestinal tract inflammation (HR, 3.00; 95% CI, 1.26–7.13; P=0.013) were predictive factors of secondary LOR.
Conclusions
Although anti-TNF-α agents contributed to long-term clinical remission of CD, the annual incidence of secondary LOR was 10.6%. The CRP/ALB ratio at 3 months after the start of biological therapy and upper gastrointestinal tract inflammation were identified as predictive factors of secondary LOR.

Citations

Citations to this article as recorded by  
  • Serum biomarkers for predicting Crohn’s disease activity: The role of bilirubin, uric acid, and the C-reactive protein/albumin ratio
    Ting Xu, Tingting Yao, Yating Chen, Fan Xu, Chunxia Lu, Aleksandra Klisic
    PLOS One.2026; 21(3): e0333855.     CrossRef
  • First-Line Guselkumab Combined with Exclusive Enteral Nutrition in Biologic-Naïve Young‑Onset Crohn’s Disease: A Three-Case Series from China
    Sumei Sha, Bin Xu, Chenyang Qiao, Kairuo Wang, Le Liu, Jie Wu, Wenqi Ma, Ameng Shi, Xin Liu
    Journal of Inflammation Research.2026; Volume 19: 1.     CrossRef
  • Risk of Spondyloarthritis in Patients With Inflammatory Bowel Disease Receiving Treatment With Biologics or Janus Kinase Inhibitors
    Young-Eun Kim, Soo Min Ahn, Ji Seon Oh, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo, Sung Wook Hwang, Byong Duk Ye, Suk-Kyun Yang, Sang Hyoung Park, Seokchan Hong
    The Journal of Rheumatology.2026; 53(3): 260.     CrossRef
  • Developing a Machine-Learning Prediction Model for Infliximab Response in Crohn’s Disease: Integrating Clinical Characteristics and Longitudinal Laboratory Trends
    Yun Qiu, Shixian Hu, Kang Chao, Lingjie Huang, Zicheng Huang, Ren Mao, Fengyuan Su, Chuhan Zhang, Xiaoqing Lin, Qian Cao, Xiang Gao, Minhu Chen
    Inflammatory Bowel Diseases.2025; 31(5): 1334.     CrossRef
  • Comparative efficacy of subcutaneous infliximab switching in remission and non-remission patients with inflammatory bowel disease after intravenous maintenance: 1-year outcome from a multicentre cohort study
    June Hwa Bae, Yoo Jin Lee, Jung-Bin Park, Ji Eun Baek, Seung Wook Hong, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Kyeong Ok Kim, Byung Ik Jang, Eun Soo Kim, Hyeong Ho Jo, Eun Young Kim, Sung Wook Hwan
    Therapeutic Advances in Gastroenterology.2025;[Epub]     CrossRef
  • The position of anti-tumor necrosis factor agents for the treatment of adult patients with Crohn’s disease
    Stephen B. Hanauer, Byong Duk Ye, Raymond K. Cross, Silvio Danese, Geert D’Haens, Jinah Jung
    Expert Review of Gastroenterology & Hepatology.2025; 19(7): 725.     CrossRef
  • Therapeutic regimen of Crohn’s disease: effect of Infliximab combined with mesalazine on intestinal flora and inflammatory indexes in patients
    Xiaoxia Xiang, Zhenghua Hu, Siyuan Dong, Bo Qi, Angyan Li, Liping Ji
    BMC Gastroenterology.2025;[Epub]     CrossRef
  • Impact of age at diagnosis on long‐term prognosis in patients with intestinal Behçet's disease
    Ji Young Chang, Soo Jung Park, Jae Jun Park, Tae Il Kim, Jae Hee Cheon, Jihye Park
    Journal of Gastroenterology and Hepatology.2024; 39(3): 519.     CrossRef
  • Effectiveness and Tolerability of Methotrexate Combined with Biologics in Patients with Crohn’s Disease: A Multicenter Observational Study
    Jihye Park, Jaeyoung Chun, Soo Jung Park, Jae Jun Park, Tae Il Kim, Hyuk Yoon, Jae Hee Cheon
    Digestive Diseases and Sciences.2024; 69(3): 901.     CrossRef
  • Effectiveness of Switching to Subcutaneous Infliximab in Ulcerative Colitis Patients Experiencing Intravenous Infliximab Failure
    June Hwa Bae, Jung-Bin Park, Ji Eun Baek, Seung Wook Hong, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Sung Wook Hwang
    Gut and Liver.2024; 18(4): 667.     CrossRef
  • Comparative real-world outcomes between ustekinumab, infliximab, and adalimumab in bio-naïve and bio-experienced Crohn’s disease patients: a retrospective multicenter study
    Ji Eun Na, Yong Eun Park, Jongha Park, Tae-Oh Kim, Jong Hoon Lee, Su Bum Park, Soyoung Kim, Seung Bum Lee
    BMC Gastroenterology.2024;[Epub]     CrossRef
  • Usefulness of Serum Leucine-rich Alpha 2 Glycoprotein in Crohn’s Disease: Is There Any Difference between Small Intestine and Colonic Lesions?
    Satohiro Matsumoto, Hirosato Mashima
    Crohn's & Colitis 360.2023;[Epub]     CrossRef
  • Enrichment of Activated Fibroblasts as a Potential Biomarker for a Non-Durable Response to Anti-Tumor Necrosis Factor Therapy in Patients with Crohn’s Disease
    Soo-Kyung Park, Gi-Young Lee, Sangsoo Kim, Chil-Woo Lee, Chang-Hwan Choi, Sang-Bum Kang, Tae-Oh Kim, Jaeyoung Chun, Jae-Myung Cha, Jong-Pil Im, Kwang-Sung Ahn, Seon-Young Kim, Min-Suk Kim, Chang-Kyun Lee, Dong-Il Park
    International Journal of Molecular Sciences.2023; 24(19): 14799.     CrossRef
  • 10,526 View
  • 471 Download
  • 14 Web of Science
  • 13 Crossref
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IBD
Trough level of infliximab is useful for assessing mucosal healing in Crohn's disease: a prospective cohort study
Akihiro Koga, Toshiyuki Matsui, Noritaka Takatsu, Yasumichi Takada, Masahiro Kishi, Yutaka Yano, Takahiro Beppu, Yoichiro Ono, Kazeo Ninomiya, Fumihito Hirai, Takashi Nagahama, Takashi Hisabe, Yasuhiro Takaki, Kenshi Yao, Hirotsugu Imaeda, Akira Andoh
Intest Res 2018;16(2):223-232.   Published online April 30, 2018
DOI: https://doi.org/10.5217/ir.2018.16.2.223
AbstractAbstract PDFSupplementary MaterialPubReaderePub
<b>Background/Aims</b><br/>

Decreased trough levels of infliximab (TLI) and antibodies to infliximab (ATI) are associated with loss of response (LOR) in Crohn's disease. Two prospective studies were conducted to determine whether TLI or ATI better correlates with LOR (Study 1), and whether TLI could become a predictor of mucosal healing (MH) (Study 2).

Methods

Study 1 was conducted in 108 patients, including those with LOR and remission to compare ATI and TLI in discriminating the 2 conditions based on receiver operating characteristic (ROC) curve analyses. Study 2 involved 35 patients who were evaluated endoscopically.

Results

In Study 1, there were no differences between the 2 assays in ROC curve analyses; the TLI cutoff value for LOR was 2.6 µg/mL (sensitivity, 70.9%; specificity, 79.2%), and the ATI cutoff value was 4.9 µg/mL (sensitivity, 65.5%; specificity, 67.9%). The AUROC (area under the ROC curve) of TLI was greater than that of ATI. AUROC was useful for discriminating between the 2 conditions. In Study 2, the TLI was significantly higher in the colonic MH group than in the non-MH group (2.7 µg/mL vs. 0.5 µg/mL, P=0.032).

Conclusions

TLI is better than ATI for clinically diagnosing LOR, and a correlation was observed between TLI and colonic MH.

Citations

Citations to this article as recorded by  
  • Mucosal and Transmural Healing and Long-term Outcomes in Crohn’s Disease
    Bruce E Sands, Silvio Danese, J Casey Chapman, Khushboo Gurjar, Stacy Grieve, Deepika Thakur, Jenny Griffith, Namita Joshi, Kristina Kligys, Axel Dignass
    Inflammatory Bowel Diseases.2025; 31(3): 857.     CrossRef
  • Is infliximab therapy currently relevant in patients with inflammatory bowel diseases? (review)
    T. L. Alexandrov, B. A. Vykova
    Koloproktologia.2024; 23(2): 173.     CrossRef
  • Expression of inflammatory mediators in biofilm samples and clinical association in inflammatory bowel disease patients—a preliminary study
    Mayte Buchbender, Jakob Fehlhofer, Peter Proff, Tobias Möst, Jutta Ries, Matthias Hannig, Markus F. Neurath, Madline Gund, Raja Atreya, Marco Kesting
    Clinical Oral Investigations.2022; 26(2): 1217.     CrossRef
  • Microbiota and Drug Response in Inflammatory Bowel Disease
    Martina Franzin, Katja Stefančič, Marianna Lucafò, Giuliana Decorti, Gabriele Stocco
    Pathogens.2021; 10(2): 211.     CrossRef
  • Post-Induction High Adalimumab Drug Levels Predict Biological Remission at Week 24 in Patients With Crohn's Disease
    Eran Zittan, A. Hillary Steinhart, Pavel Goldstein, Raquel Milgrom, Ian M. Gralnek, Mark S. Silverberg
    Clinical and Translational Gastroenterology.2021; 12(10): e00401.     CrossRef
  • Potential Utility of Therapeutic Drug Monitoring of Adalimumab in Predicting Short-Term Mucosal Healing and Histologic Remission in Pediatric Crohn's Disease Patients
    So Yoon Choi, Young Ok Choi, Yon Ho Choe, Ben Kang
    Journal of Korean Medical Science.2020;[Epub]     CrossRef
  • Clinical and laboratory markers associated with anti-TNF-alpha trough levels and anti-drug antibodies in patients with inflammatory bowel diseases
    Ana B. Grinman, Maria das Graças C. de Souza, Eliete Bouskela, Ana Teresa P. Carvalho, Heitor S. P. de Souza
    Medicine.2020; 99(10): e19359.     CrossRef
  • Changes in the Intestinal Microbiota of Patients with Inflammatory Bowel Disease with Clinical Remission during an 8-Week Infliximab Infusion Cycle
    Gyeol Seong, Namil Kim, Je-Gun Joung, Eun Ran Kim, Dong Kyung Chang, Jongsik Chun, Sung Noh Hong, Young-Ho Kim
    Microorganisms.2020; 8(6): 874.     CrossRef
  • Patient sex does not affect endoscopic outcomes of biologicals in inflammatory bowel disease but is associated with adverse events
    Mitchell R. K. L. Lie, Emma Paulides, C. Janneke van der Woude
    International Journal of Colorectal Disease.2020; 35(8): 1489.     CrossRef
  • Association of Infliximab Levels With Mucosal Healing Is Time-Dependent in Crohn’s Disease: Higher Drug Exposure Is Required Postinduction Than During Maintenance Treatment
    Ting Feng, Baili Chen, Bella Ungar, Yun Qiu, Shenghong Zhang, Jinshen He, Sinan Lin, Yao He, Zhirong Zeng, Shomron Ben-Horin, Minhu Chen, Ren Mao
    Inflammatory Bowel Diseases.2019; 25(11): 1813.     CrossRef
  • Mucosal healing in inflammatory bowel disease: Expanding horizon
    Jimil Shah, Manik Lal Thakur, Usha Dutta
    Indian Journal of Gastroenterology.2019; 38(2): 98.     CrossRef
  • 9,993 View
  • 79 Download
  • 10 Web of Science
  • 11 Crossref
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