Year 2020 / Volume 112 / Number 5
Original
Usefulness of therapeutic drug monitoring of infliximab during the induction period in patients with inflammatory bowel disease

360-366

DOI: 10.17235/reed.2020.6618/2019

Mayte Gil Candel, Juan José Gascón Cánovas, Elena Urbieta Sanz, Rosa Gómez Espín, Isabel Nicolás de Prado, Carles Iniesta Navalón,

Abstract
Introduction: previous studies have shown that higher infliximab trough levels are associated with favorable short-term and long-term therapeutic outcomes in inflammatory bowel disease. There is a need to determine which patients could benefit from proactive therapeutic drug monitoring in the induction phase. The aim of this study was to evaluate the pharmacokinetic variability of infliximab, determine the factors associated with achieving target infliximab trough levels in the induction phase and analyze the clinical and biochemical response at week 26 of treatment. Patients and methods: a retrospective observational study was performed of patients with inflammatory bowel disease and data available on serum levels of infliximab during the induction period. The percentage of patients that achieved target infliximab trough levels at week 6 was determined. Clinical remission and response and biochemical remission were evaluated at week 26. Results: thirty patients were included and only 13 (43.3 %) had infliximab trough levels > 15 µg/mL at week 6. A clinical response was observed during the maintenance period in 71.4 % of patients, their infliximab levels were significantly higher than in non-responders (6.3 µg/mL [IQR: 6.7] vs 1.0 µg/mL [IQR: 5.0], respectively; p = 0.016). Likewise, 53.6 % of patients achieved biochemical remission (responders 6.2 µg/mL [IQR: 5.2] vs non-responders 3.2 µg/mL [IQR: 5.0]; p = 0.031). Conclusion: less than half of patients had target infliximab levels during the induction period. Therapeutic drug monitoring during this period is related to the achievement of therapeutic levels of infliximab and may lead to a better clinical response in these patients.
Share Button
New comment
Comments

10/06/2020 20:26:32
Good


References
1. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med 2005; 353:2462–76. https://doi.org/10.1056/NEJMoa050516
2. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: The ACCENT I randomised trial. Lancet 2002; 359:1541–9. https://doi.org/10.1016/S0140-6736(02)08512-4
3. Ford AC, Sandborn WJ, Khan KJ, et al. Efficacy of Biological Therapies in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis. Am J Gastroenterol 2011; 106:644–59. https://doi.org/10.1038/ajg.2011.73
4. Papamichael K, Cheifetz AS, Melmed GY, et al. Appropriate Therapeutic Drug Monitoring of Biologic Agents for Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol 2019; 17:1655-68. https://doi.org/10.1016/j.cgh.2019.03.037
5. Beltrán B, Iborra M, Sáez-González E, et al. Fecal Calprotectin Pretreatment and Induction Infliximab Levels for Prediction of Primary Nonresponse to Infliximab Therapy in Crohn’s Disease. Dig Dis 2019; 37:108–15. https://doi.org/10.1159/000492626
6. Zhang QW, Shen J, Zheng Q, Ran ZH. Loss of response to scheduled infliximab therapy for Crohn’s disease in adults: A systematic review and meta-analysis. J. Dig. Dis 2019; 20:65–72. DOI: 10.1111/1751-2980.12698.
7. Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology 2015; 148:1320-9. https://doi.org/10.1053/j.gastro.2015.02.031
8. Steenholdt C, Brynskov J, Thomsen OO, et al. Individualised therapy is more cost-effective than dose intensification in patients with Crohn’s disease who lose response to anti-TNF treatment: A randomised, controlled trial. Gut 2014; 63:919–27. https://doi.org/10.1136/gutjnl-2013-305279
9. Brandse JF, Mathôt RA, Kleij D Van Der, et al. Pharmacokinetic Features and Presence of Antidrug Antibodies Associate With Response to Infliximab Induction Therapy in Patients With Moderate to Severe Ulcerative Colitis. Clin Gastroenterol Hepatol 2019; 14:251-8. https://doi.org/10.1016/j.cgh.2015.10.029
10. Brandse JF, Brink GR Van Den, Wildenberg ME, et al. Loss of In fl iximab Into Feces Is Associated With Lack of Response to Therapy in Patients With Severe Ulcerative Colitis. Gastroenterology 2015; 149:350-5 https://doi.org/10.1053/j.gastro.2015.04.016
11. Fasanmade AA, Adedokun OJ, Blank M, et al. Pharmacokinetic Properties of Infliximab in Children and Adults with Crohn’s Disease: A Retrospective Analysis of Data from 2 Phase III Clinical Trials. Clin Ther 2011; 33:946–64. https://doi.org/10.1016/j.clinthera.2011.06.002
12. Flamant M, Roblin X. Inflammatory bowel disease: towards a personalized medicine. Therap Adv Gastroenterol 2018; 11: 1-15. https://doi.org/10.1177/1756283X17745029
13. Kampa KC, Morsoletto DBG, Loures MR, et al. Importance of measuring levels of infliximab in patients treating inflammatory bowel disease in a Brazilian cohort. Arq Gastroenterol 2017; 54:333–7. https://doi.org/10.1590/s0004-2803.201700000-41
14. Hoeve K van, Dreesen E, Hoffman I, et al. Adequate Infliximab Exposure During Induction Predicts. J Pediatr Gastroenterol Nutr 2019; 68:847–53. https://doi.org/DOI: 10.1097/MPG.0000000000002265
15. Davidov Y, Ungar B, Bar-Yoseph H, et al. Association of Induction Infliximab Levels With Clinical Response in Perianal Crohn’s Disease. J Crohns Colitis 2017; 11:549–55. https://doi.org/10.1093/ecco-jcc/jjw182
16. Dreesen E, Faelens R, Van Assche G, et al. Optimising infliximab induction dosing for patients with ulcerative colitis. Br J Clin Pharmacol 2019; 85:782–95. https://doi.org/10.1111/bcp.13859
17. Papamichael K, Stappen T Van, Casteele N Vande, et al. Infliximab Concentration Thresholds During Induction Therapy Are Associated With Short-term Mucosal Healing in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol 2016; 14:543–9. https://doi.org/10.1016/j.cgh.2015.11.014
18. Papamichael K, Casteele N Vande, Ferrante M, et al. Therapeutic Drug Monitoring during Induction of Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Disease: Defining a Therapeutic Drug Window. Inflamm. Bowel Dis. 2017; 23:1510–5
19. Santacana E, Rodríguez-Alonso L, Padullés A, et al. External Evaluation of Population Pharmacokinetic Models of Infliximab in Patients With Inflammatory Bowel Disease. Ther Drug Monit 2018; 40:120–9. https://doi.org/10.1097/FTD.0000000000000476
20. Martínez-Romero GJ, Alvariño A, Hinojosa E, et al. Validation of a population pharmacokinetic model of adalimumab in a cohort of patients with inflammatory bowel disease. Rev Esp Enferm Dig 2019; 111:431-6 https://doi.org/10.17235/reed.2019.5600/2018
21. Sparrow MP, Papamichael K, Ward MG, et al. Therapeutic Drug Monitoring of Biologics During Induction to Prevent Primary Non-Response. J Crohn’s Colitis 2019. https://doi: 10.1093/ecco-jcc/jjz162. [Epub ahead of print]
22. Satsangi J, Silverberg MS, Vermeire S, et al. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006; 55:749–53. https://doi.org/10.1136/gut.2005.082909
23. Mitrev N, Vande Casteele N, Seow CH, et al. Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases. Aliment Pharmacol Ther 2017; 46:1037–53. https://doi.org/10.1111/apt.14368
24. Huang VW, Prosser C, Kroeker KI, et al. Knowledge of fecal calprotectin and infliximab trough levels alters clinical decision-making for IBD outpatients on maintenance infliximab therapy. Inflamm Bowel Dis 2015; 21:1359–67. https://doi.org/10.1097/MIB.0000000000000376
25. DʼHaens G, Ferrante M, Vermeire S, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012; 18:2218–24. https://doi.org/10.1002/ibd.22917
26. Bar-Yoseph H, Levhar N, Selinger L, et al. Early drug and anti-infliximab antibody levels for prediction of primary nonresponse to infliximab therapy. Aliment Pharmacol Ther 2018; 47:212–8. https://doi.org/10.1111/apt.14410
27. Kobayashi T, Suzuki Y, Motoya S, et al. First trough level of infliximab at week 2 predicts future outcomes of induction therapy in ulcerative colitis—results from a multicenter prospective randomized controlled trial and its post hoc analysis. J Gastroenterol 2016; 51:241–51. https://doi.org/10.1007/s00535-015-1102-z
28. Lega S, Phan BL, Rosenthal CJ, et al. Proactively Optimized Infliximab Monotherapy Is as Effective as Combination Therapy in IBD. Inflamm Bowel Dis 2019; 25:134–41. https://doi.org/10.1093/ibd/izy203
29. Tighe D, Smith S, O’Connor A, et al. Positive relationship between infliximab and adalimumab trough levels at completion of induction therapy with clinical response rates, at a tertiary referral center. JGH Open 2017; 1:4–10. https://doi.org/10.1002/jgh3.12000
30. Kennedy NA, Heap GA, Green HD, et al. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn’s disease: a prospective, multicentre, cohort study. Lancet Gastroenterol Hepatol 2019; 4:341–53. https://doi.org/10.1016/S2468-1253(19)30012-3
31. Dotan I, Ron Y, Yanai H, et al. Patient factors that increase infliximab clearance and shorten half-life in inflammatory bowel disease: a population pharmacokinetic study. Inflamm Bowel Dis 2014; 20:2247–59. https://doi.org/10.1097/MIB.0000000000000212
32. Kheir N, Awaisu A, Gad H, et al. Clinical pharmacokinetics: perceptions of hospital pharmacists in Qatar about how it was taught and how it is applied. Int J Clin Pharm 2015; 37:1180–7. https://doi.org/10.1007/s11096-015-0183-3
33. Frymoyer A, Hoekman DR, Piester TL, et al. Application of Population Pharmacokinetic Modeling for Individualized Infliximab Dosing Strategies in Crohn Disease. J Pediatr Gastroenterol Nutr 2017; 65:639–45. https://doi.org/10.1097/MPG.0000000000001620
34. Raimundo Fernandes S, Bernardo S, Simões C, et al. Proactive infliximab drug monitoring is superior to conventional management in inflammatory bowel disease. J Crohn’s Colitis 2019. https://doi: 10.1093/ibd/izz131. [Epub ahead of print].
35. Feuerstein JD, Nguyen GC, Kupfer SS, et al. American Gastroenterological Association Institute Guideline on Therapeutic Drug Monitoring in Inflammatory Bowel Disease. Gastroenterology 2017; 153:827–34. https://doi.org/10.1053/j.gastro.2017.07.032
Related articles

Letter

Hepatosplenic T-cell lymphoma and inflammatory bowel disease

DOI: 10.17235/reed.2023.9472/2023

Review

Clinical settings with tofacitinib in ulcerative colitis

DOI: 10.17235/reed.2022.8660/2022

Letter

Anal neoplasia and perianal Crohn’s disease: myth or reality?

DOI: 10.17235/reed.2021.8317/2021

Letter

Apoptotic colopathy as a manifestation of Good’s syndrome

DOI: 10.17235/reed.2021.8297/2021

Original

Radon exposure and inflammatory bowel disease in a radon prone area

DOI: 10.17235/reed.2021.8239/2021

Review

Inflammatory bowel disease and solid organ transplantation

DOI: 10.17235/reed.2020.7361/2020

Editorial

Is celiac disease really associated with inflammatory bowel disease?

DOI: 10.17235/reed.2019.6779/2019

Original

Megacolon in inflammatory bowel disease: response to infliximab

DOI: 10.17235/reed.2020.6394/2019

Editorial

Diet in the etiology of inflammatory bowel disease

DOI: 10.17235/reed.2018.6119/2018

Case Report

Serrated Lesions in patients with Inflammatory Bowel Disease.

DOI: 10.17235/reed.2019.5910/2018

Editorial

Online social networks and inflammatory bowel disease

DOI: 10.17235/reed.2018.5496/2018

Letter to the Editor

Idiopathic portal hypertension with regard to thiopurine treatment

DOI: 10.17235/reed.2018.5256/2017

Editorial

Specialist care in the management of inflammatory bowel disease

DOI: 10.17235/reed.2016.4628/2016

Citation tools
Gil Candel M, Gascón Cánovas J, Urbieta Sanz E, Gómez Espín R, Nicolás de Prado I, Iniesta Navalón C, et all. Usefulness of therapeutic drug monitoring of infliximab during the induction period in patients with inflammatory bowel disease. 6618/2019


Download to a citation manager

Download the citation for this article by clicking on one of the following citation managers:

Metrics
This article has received 1303 visits.
This article has been downloaded 214 times.

Statistics from Dimensions


Statistics from Plum Analytics

Publication history

Received: 08/09/2019

Accepted: 11/11/2019

Online First: 27/04/2020

Published: 08/05/2020

Article revision time: 62 days

Article Online First time: 232 days

Article editing time: 243 days


Share
This article has been rated by 1 readers.
Reader rating:
Valora este artículo:




Asociación Española de Ecografía Digestiva Sociedad Española de Endoscopia Digestiva Sociedad Española de Patología Digestiva
The Spanish Journal of Gastroenterology is the official organ of the Sociedad Española de Patología Digestiva, the Sociedad Española de Endoscopia Digestiva and the Asociación Española de Ecografía Digestiva
Cookie policy Privacy Policy Legal Notice © Copyright 2023 y Creative Commons. The Spanish Journal of Gastroenterology