Anti-TNF therapeutic drug monitoring in postoperative Crohn's disease

Emily K. Wright, Michael A. Kamm, Peter De Cruz, Amy L. Hamilton, Fabiyola Selvaraj, Fred Princen, Alexandra Gorelik, Danny Liew, Lani Prideaux, Ian C. Lawrance, Jane M. Andrews, Peter A. Bampton, Simon L. Jakobovits, Timothy H. Florin, Peter R. Gibson, Henry Debinski, Finlay A. Macrae, Douglas Samuel, Ian Kronborg, Graham Radford-Smith & 5 others Richard B. Gearry, Warwick Selby, Sally J. Bell, Steven J. Brown, William R. Connell

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Abstract

Background: Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence. Methods: As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months. Results: Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts = i2] [9.98μg/mL vs 8.43 μg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 μg/mL] than patients on combination therapy [11.725 μg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31% vs 17%, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 μg/mL vs 12.0 μg/mL, p < 0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046]. Conclusion: Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.

Original languageEnglish
Pages (from-to)653-661
Number of pages9
JournalJournal of Crohn's and Colitis
Volume12
Issue number6
DOIs
Publication statusPublished - 25 May 2018

Keywords

  • Adalimumab
  • Anti-TNF
  • Inflammatory Bowel Disease
  • Therapeutic drug monitoring

Cite this

Wright, E. K., Kamm, M. A., De Cruz, P., Hamilton, A. L., Selvaraj, F., Princen, F., ... Connell, W. R. (2018). Anti-TNF therapeutic drug monitoring in postoperative Crohn's disease. Journal of Crohn's and Colitis, 12(6), 653-661. https://doi.org/10.1093/ecco-jcc/jjy003
Wright, Emily K. ; Kamm, Michael A. ; De Cruz, Peter ; Hamilton, Amy L. ; Selvaraj, Fabiyola ; Princen, Fred ; Gorelik, Alexandra ; Liew, Danny ; Prideaux, Lani ; Lawrance, Ian C. ; Andrews, Jane M. ; Bampton, Peter A. ; Jakobovits, Simon L. ; Florin, Timothy H. ; Gibson, Peter R. ; Debinski, Henry ; Macrae, Finlay A. ; Samuel, Douglas ; Kronborg, Ian ; Radford-Smith, Graham ; Gearry, Richard B. ; Selby, Warwick ; Bell, Sally J. ; Brown, Steven J. ; Connell, William R. / Anti-TNF therapeutic drug monitoring in postoperative Crohn's disease. In: Journal of Crohn's and Colitis. 2018 ; Vol. 12, No. 6. pp. 653-661.
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title = "Anti-TNF therapeutic drug monitoring in postoperative Crohn's disease",
abstract = "Background: Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence. Methods: As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months. Results: Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts = i2] [9.98μg/mL vs 8.43 μg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 μg/mL] than patients on combination therapy [11.725 μg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31{\%} vs 17{\%}, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 μg/mL vs 12.0 μg/mL, p < 0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046]. Conclusion: Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.",
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author = "Wright, {Emily K.} and Kamm, {Michael A.} and {De Cruz}, Peter and Hamilton, {Amy L.} and Fabiyola Selvaraj and Fred Princen and Alexandra Gorelik and Danny Liew and Lani Prideaux and Lawrance, {Ian C.} and Andrews, {Jane M.} and Bampton, {Peter A.} and Jakobovits, {Simon L.} and Florin, {Timothy H.} and Gibson, {Peter R.} and Henry Debinski and Macrae, {Finlay A.} and Douglas Samuel and Ian Kronborg and Graham Radford-Smith and Gearry, {Richard B.} and Warwick Selby and Bell, {Sally J.} and Brown, {Steven J.} and Connell, {William R.}",
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Wright, EK, Kamm, MA, De Cruz, P, Hamilton, AL, Selvaraj, F, Princen, F, Gorelik, A, Liew, D, Prideaux, L, Lawrance, IC, Andrews, JM, Bampton, PA, Jakobovits, SL, Florin, TH, Gibson, PR, Debinski, H, Macrae, FA, Samuel, D, Kronborg, I, Radford-Smith, G, Gearry, RB, Selby, W, Bell, SJ, Brown, SJ & Connell, WR 2018, 'Anti-TNF therapeutic drug monitoring in postoperative Crohn's disease', Journal of Crohn's and Colitis, vol. 12, no. 6, pp. 653-661. https://doi.org/10.1093/ecco-jcc/jjy003

Anti-TNF therapeutic drug monitoring in postoperative Crohn's disease. / Wright, Emily K.; Kamm, Michael A.; De Cruz, Peter; Hamilton, Amy L.; Selvaraj, Fabiyola; Princen, Fred; Gorelik, Alexandra; Liew, Danny; Prideaux, Lani; Lawrance, Ian C.; Andrews, Jane M.; Bampton, Peter A.; Jakobovits, Simon L.; Florin, Timothy H.; Gibson, Peter R.; Debinski, Henry; Macrae, Finlay A.; Samuel, Douglas; Kronborg, Ian; Radford-Smith, Graham; Gearry, Richard B.; Selby, Warwick; Bell, Sally J.; Brown, Steven J.; Connell, William R.

In: Journal of Crohn's and Colitis, Vol. 12, No. 6, 25.05.2018, p. 653-661.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Anti-TNF therapeutic drug monitoring in postoperative Crohn's disease

AU - Wright, Emily K.

AU - Kamm, Michael A.

AU - De Cruz, Peter

AU - Hamilton, Amy L.

AU - Selvaraj, Fabiyola

AU - Princen, Fred

AU - Gorelik, Alexandra

AU - Liew, Danny

AU - Prideaux, Lani

AU - Lawrance, Ian C.

AU - Andrews, Jane M.

AU - Bampton, Peter A.

AU - Jakobovits, Simon L.

AU - Florin, Timothy H.

AU - Gibson, Peter R.

AU - Debinski, Henry

AU - Macrae, Finlay A.

AU - Samuel, Douglas

AU - Kronborg, Ian

AU - Radford-Smith, Graham

AU - Gearry, Richard B.

AU - Selby, Warwick

AU - Bell, Sally J.

AU - Brown, Steven J.

AU - Connell, William R.

PY - 2018/5/25

Y1 - 2018/5/25

N2 - Background: Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence. Methods: As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months. Results: Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts = i2] [9.98μg/mL vs 8.43 μg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 μg/mL] than patients on combination therapy [11.725 μg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31% vs 17%, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 μg/mL vs 12.0 μg/mL, p < 0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046]. Conclusion: Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.

AB - Background: Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence. Methods: As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months. Results: Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts = i2] [9.98μg/mL vs 8.43 μg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 μg/mL] than patients on combination therapy [11.725 μg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31% vs 17%, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 μg/mL vs 12.0 μg/mL, p < 0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046]. Conclusion: Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.

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KW - Anti-TNF

KW - Inflammatory Bowel Disease

KW - Therapeutic drug monitoring

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Wright EK, Kamm MA, De Cruz P, Hamilton AL, Selvaraj F, Princen F et al. Anti-TNF therapeutic drug monitoring in postoperative Crohn's disease. Journal of Crohn's and Colitis. 2018 May 25;12(6):653-661. https://doi.org/10.1093/ecco-jcc/jjy003