Abstract | BACKGROUND & AIMS: METHODS: We performed a retrospective cross-sectional study of 145 patients with IBD treated with infliximab (n = 78) or adalimumab (n = 67) at a medical center in Israel from 2009 through 2014. We collected data from colonoscopy examinations; mucosal healing was defined as simple endoscopic score of <3 or a Mayo score ≤1. These data were compared with serum levels of anti- tumor necrosis factor agents, clinical scores, and levels of C-reactive protein. RESULTS: Median serum levels of infliximab and adalimumab were significantly higher in patients with mucosal healing than patients with active disease (based on endoscopy) (for infliximab, 4.3 vs 1.7 μg/mL, P = .0002; for adalimumab, 6.2 vs 3.1 μg/mL, P = .01). Levels of infliximab above 5 μg/mL (area under the curve = 0.75; P < .0001) and levels of adalimumab above 7.1 μg/mL (area under the curve = 0.7; P = .004) identified patients with mucosal healing with 85% specificity. Increasing levels of infliximab beyond 8 μg/mL produced only minimal increases in the rate of mucosal healing, whereas the association between higher level of adalimumab and increased rate of mucosal healing reached a plateau at 12 μg/mL. In patients with measurable levels of infliximab >3 μg/mL, the presence of antibodies to infliximab was associated with a lower rate of mucosal healing compared with patients with similar drug level without antibodies (16% vs 50%, respectively; P = .003). CONCLUSIONS: In a retrospective study, we found significant association between serum levels of anti- tumor necrosis factor agents and level of mucosal healing. We propose that serum levels of 6-10 μg/mL for infliximab and 8-12 μg/mL for adalimumab are required to achieve mucosal healing in 80%-90% of patients with IBD, and that this could be considered as a "therapeutic window." Exceeding these levels produces only a negligible gain in proportion of patients with mucosal healing.
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Authors | Bella Ungar, Idan Levy, Yarden Yavne, Miri Yavzori, Orit Picard, Ella Fudim, Ronen Loebstein, Yehuda Chowers, Rami Eliakim, Uri Kopylov, Shomron Ben-Horin |
Journal | Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
(Clin Gastroenterol Hepatol)
Vol. 14
Issue 4
Pg. 550-557.e2
(Apr 2016)
ISSN: 1542-7714 [Electronic] United States |
PMID | 26538204
(Publication Type: Journal Article, Observational Study)
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Copyright | Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Immunosuppressive Agents
- Tumor Necrosis Factor-alpha
- C-Reactive Protein
- Infliximab
- Adalimumab
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Topics |
- Adalimumab
(administration & dosage, blood)
- Adult
- C-Reactive Protein
(analysis)
- Colonoscopy
- Cross-Sectional Studies
- Female
- Humans
- Immunomodulation
- Immunosuppressive Agents
(administration & dosage, blood)
- Inflammatory Bowel Diseases
(drug therapy)
- Infliximab
(administration & dosage, blood, pharmacokinetics)
- Intestinal Mucosa
(pathology)
- Israel
- Male
- Middle Aged
- Retrospective Studies
- Serum
(chemistry)
- Severity of Illness Index
- Treatment Outcome
- Tumor Necrosis Factor-alpha
(antagonists & inhibitors)
- Young Adult
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