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

doi:10.1093/ibd/izz061

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^*

^*Corresponding author for this work

Internal Medicine

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Infliximab levels have been reported to be associated with mucosal healing (MH) in Crohn's disease (CD). However, whether the association differs between postinduction (week 14) and maintenance (week 30) has seldom been investigated. We aimed to analyze the association between serum infliximab trough levels and MH at the 2 different time points. Methods: A retrospective study of CD patients treated with infliximab in a tertiary referral center between January 2012 and May 2018 was conducted. MH was defined as absence of ulceration by endoscopy. Correlations between infliximab level and MH were investigated at 2 specific time points, weeks 14 and 30. Results: Median infliximab levels were higher in patients with MH than those without at weeks 14 (7.5 vs 1.5 μg/mL; P < 0.001) and 30 (5.9 vs 0.5 μg/mL; P < 0.001). The median levels in patients with MH at week 14 were higher than at week 30 (7.5 vs 5.9 μg/mL; P < 0.05). Multivariate analysis showed that infliximab level was independently associated with MH (both P < 0.001 at weeks 14 and 30). Infliximab level above 4.85 μg/mL and 2.85 μg/mL identified patients with MH at week 14 (area under the curve [AUC], 0.796; P < 0.001) and week 30 (AUC, 0.780; P < 0.001) with 80% specificity. The rates of MH reached a plateau (>85%) when infliximab levels were above 10 and 6 μg/mL at weeks 14 and 30, respectively. Conclusions: Infliximab levels correlated with MH at weeks 14 and 30 in CD patients. Higher levels might be required to achieve MH at postinduction than during maintenance treatment.

Original language	English
Pages (from-to)	1813-1821
Number of pages	9
Journal	Inflammatory Bowel Diseases
Volume	25
Issue number	11
DOIs	https://doi.org/10.1093/ibd/izz061
State	Published - 18 Oct 2019

Funding

Funders	Funder number
National Natural Science Foundation of China	81600508, 81500501, 81601514

Keywords

Crohn's disease
infliximab
mucosal healing

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10.1093/ibd/izz061

Cite this

Feng, T., Chen, B., Ungar, B., Qiu, Y., Zhang, S., He, J., Lin, S., He, Y., Zeng, Z., Ben-Horin, S., Chen, M., & Mao, R. (2019). Association of Infliximab Levels with Mucosal Healing Is Time-Dependent in Crohn's Disease: Higher Drug Exposure Is Required Postinduction Than during Maintenance Treatment. Inflammatory Bowel Diseases, 25(11), 1813-1821. https://doi.org/10.1093/ibd/izz061

@article{b71833f42e594b49b9c0c1e17ce1cc3b,

title = "Association of Infliximab Levels with Mucosal Healing Is Time-Dependent in Crohn's Disease: Higher Drug Exposure Is Required Postinduction Than during Maintenance Treatment",

abstract = "Infliximab levels have been reported to be associated with mucosal healing (MH) in Crohn's disease (CD). However, whether the association differs between postinduction (week 14) and maintenance (week 30) has seldom been investigated. We aimed to analyze the association between serum infliximab trough levels and MH at the 2 different time points. Methods: A retrospective study of CD patients treated with infliximab in a tertiary referral center between January 2012 and May 2018 was conducted. MH was defined as absence of ulceration by endoscopy. Correlations between infliximab level and MH were investigated at 2 specific time points, weeks 14 and 30. Results: Median infliximab levels were higher in patients with MH than those without at weeks 14 (7.5 vs 1.5 μg/mL; P < 0.001) and 30 (5.9 vs 0.5 μg/mL; P < 0.001). The median levels in patients with MH at week 14 were higher than at week 30 (7.5 vs 5.9 μg/mL; P < 0.05). Multivariate analysis showed that infliximab level was independently associated with MH (both P < 0.001 at weeks 14 and 30). Infliximab level above 4.85 μg/mL and 2.85 μg/mL identified patients with MH at week 14 (area under the curve [AUC], 0.796; P < 0.001) and week 30 (AUC, 0.780; P < 0.001) with 80% specificity. The rates of MH reached a plateau (>85%) when infliximab levels were above 10 and 6 μg/mL at weeks 14 and 30, respectively. Conclusions: Infliximab levels correlated with MH at weeks 14 and 30 in CD patients. Higher levels might be required to achieve MH at postinduction than during maintenance treatment.",

keywords = "Crohn's disease, infliximab, mucosal healing",

author = "Ting Feng and Baili Chen and Bella Ungar and Yun Qiu and Shenghong Zhang and Jinshen He and Sinan Lin and Yao He and Zhirong Zeng and Shomron Ben-Horin and Minhu Chen and Ren Mao",

year = "2019",

month = oct,

day = "18",

doi = "10.1093/ibd/izz061",

language = "אנגלית",

volume = "25",

pages = "1813--1821",

journal = "Inflammatory Bowel Diseases",

issn = "1078-0998",

publisher = "Oxford University Press",

number = "11",

}

Feng, T, Chen, B, Ungar, B, Qiu, Y, Zhang, S, He, J, Lin, S, He, Y, Zeng, Z, Ben-Horin, S, Chen, M & Mao, R 2019, 'Association of Infliximab Levels with Mucosal Healing Is Time-Dependent in Crohn's Disease: Higher Drug Exposure Is Required Postinduction Than during Maintenance Treatment', Inflammatory Bowel Diseases, vol. 25, no. 11, pp. 1813-1821. https://doi.org/10.1093/ibd/izz061

TY - JOUR

T1 - Association of Infliximab Levels with Mucosal Healing Is Time-Dependent in Crohn's Disease

T2 - Higher Drug Exposure Is Required Postinduction Than during Maintenance Treatment

AU - Feng, Ting

AU - Chen, Baili

AU - Ungar, Bella

AU - Qiu, Yun

AU - Zhang, Shenghong

AU - He, Jinshen

AU - Lin, Sinan

AU - He, Yao

AU - Zeng, Zhirong

AU - Ben-Horin, Shomron

AU - Chen, Minhu

AU - Mao, Ren

PY - 2019/10/18

Y1 - 2019/10/18

N2 - Infliximab levels have been reported to be associated with mucosal healing (MH) in Crohn's disease (CD). However, whether the association differs between postinduction (week 14) and maintenance (week 30) has seldom been investigated. We aimed to analyze the association between serum infliximab trough levels and MH at the 2 different time points. Methods: A retrospective study of CD patients treated with infliximab in a tertiary referral center between January 2012 and May 2018 was conducted. MH was defined as absence of ulceration by endoscopy. Correlations between infliximab level and MH were investigated at 2 specific time points, weeks 14 and 30. Results: Median infliximab levels were higher in patients with MH than those without at weeks 14 (7.5 vs 1.5 μg/mL; P < 0.001) and 30 (5.9 vs 0.5 μg/mL; P < 0.001). The median levels in patients with MH at week 14 were higher than at week 30 (7.5 vs 5.9 μg/mL; P < 0.05). Multivariate analysis showed that infliximab level was independently associated with MH (both P < 0.001 at weeks 14 and 30). Infliximab level above 4.85 μg/mL and 2.85 μg/mL identified patients with MH at week 14 (area under the curve [AUC], 0.796; P < 0.001) and week 30 (AUC, 0.780; P < 0.001) with 80% specificity. The rates of MH reached a plateau (>85%) when infliximab levels were above 10 and 6 μg/mL at weeks 14 and 30, respectively. Conclusions: Infliximab levels correlated with MH at weeks 14 and 30 in CD patients. Higher levels might be required to achieve MH at postinduction than during maintenance treatment.

AB - Infliximab levels have been reported to be associated with mucosal healing (MH) in Crohn's disease (CD). However, whether the association differs between postinduction (week 14) and maintenance (week 30) has seldom been investigated. We aimed to analyze the association between serum infliximab trough levels and MH at the 2 different time points. Methods: A retrospective study of CD patients treated with infliximab in a tertiary referral center between January 2012 and May 2018 was conducted. MH was defined as absence of ulceration by endoscopy. Correlations between infliximab level and MH were investigated at 2 specific time points, weeks 14 and 30. Results: Median infliximab levels were higher in patients with MH than those without at weeks 14 (7.5 vs 1.5 μg/mL; P < 0.001) and 30 (5.9 vs 0.5 μg/mL; P < 0.001). The median levels in patients with MH at week 14 were higher than at week 30 (7.5 vs 5.9 μg/mL; P < 0.05). Multivariate analysis showed that infliximab level was independently associated with MH (both P < 0.001 at weeks 14 and 30). Infliximab level above 4.85 μg/mL and 2.85 μg/mL identified patients with MH at week 14 (area under the curve [AUC], 0.796; P < 0.001) and week 30 (AUC, 0.780; P < 0.001) with 80% specificity. The rates of MH reached a plateau (>85%) when infliximab levels were above 10 and 6 μg/mL at weeks 14 and 30, respectively. Conclusions: Infliximab levels correlated with MH at weeks 14 and 30 in CD patients. Higher levels might be required to achieve MH at postinduction than during maintenance treatment.

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KW - mucosal healing

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SN - 1078-0998

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ER -

Association of Infliximab Levels with Mucosal Healing Is Time-Dependent in Crohn's Disease: Higher Drug Exposure Is Required Postinduction Than during Maintenance Treatment

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