Higher adalimumab drug levels are associated with mucosal healing in patients with Crohn's disease

E. Zittan, B. Kabakchiev, R. Milgrom, G. C. Nguyen, K. Croitoru, A. H. Steinhart, M. S. Silverberg

Research output: Contribution to journalArticle

Abstract

Background and aims: The current approach to managing the loss of response to anti-tumour necrosis factor (TNF) agents is generally empirical. Prior studies have suggested that adalimumab levels of >4.9 μg/mL are required to achieve clinical remission. Our aim was to identify an optimal adalimumab level to achieve endoscopic healing in Crohn's disease (CD). Methods: A cohort of 60 CD patients treated with adalimumab between 2005 and 2013 were reviewed for the study. Demographic and clinical information was obtained from chart review and patient interview. Disease activity was determined using the Harvey-Bradshaw index (HBI), ileocolonoscopy reports and C-reactive protein (CRP) levels. Clinical remission was defined as HBI <5. Endoscopic remission/mucosal healing (MH) was defined as the absence of any ulceration in all ileocolonic segments. Trough adalimumab levels and adalimumab antibody levels were tested using a liquid-phase mobility shift assay. Results: Lower median CRP was significantly associated with MH 1.2mg/dl vs no MH 14.4mg/dl (p = 6.93×10-6). Higher adalimumab trough level was significantly associated with MH (median 14.7 μg/mL in those with MH vs 3.4 μg/mL in those without, p = 6.25×10-5). Higher adalimumab trough level was also significantly associated with the combined outcome of clinical and endoscopic remission (median 13.0 vs 4.8 μg/mL, p = 5.36×10-3). A cut-off of 8.14 μg/ml best discriminated subjects with MH from those without MH, with sensitivity and specificity of 91.4 and 76.0%, respectively (positive and negative predictive values 84.2 and 86.4%, respectively). Conclusions: Higher adalimumab levels were significantly associated with MH. This study suggests that attaining MH alone or a combined outcome of clinical and endoscopic remission is more likely to occur in those patients who achieve an adalimumab trough level of at least 8.14 μg/mL.

Original languageEnglish (US)
Pages (from-to)510-515
Number of pages6
JournalJournal of Crohn's and Colitis
Volume10
Issue number5
DOIs
StatePublished - May 1 2016
Externally publishedYes

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Crohn Disease
Pharmaceutical Preparations
C-Reactive Protein
Adalimumab
Electrophoretic Mobility Shift Assay
Tumor Necrosis Factor-alpha
Demography
Interviews
Sensitivity and Specificity
Antibodies

Keywords

  • Adalimumab
  • Crohn's disease
  • Endoscopic remission

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Zittan, E., Kabakchiev, B., Milgrom, R., Nguyen, G. C., Croitoru, K., Steinhart, A. H., & Silverberg, M. S. (2016). Higher adalimumab drug levels are associated with mucosal healing in patients with Crohn's disease. Journal of Crohn's and Colitis, 10(5), 510-515. https://doi.org/10.1093/ecco-jcc/jjw014

Higher adalimumab drug levels are associated with mucosal healing in patients with Crohn's disease. / Zittan, E.; Kabakchiev, B.; Milgrom, R.; Nguyen, G. C.; Croitoru, K.; Steinhart, A. H.; Silverberg, M. S.

In: Journal of Crohn's and Colitis, Vol. 10, No. 5, 01.05.2016, p. 510-515.

Research output: Contribution to journalArticle

Zittan, E, Kabakchiev, B, Milgrom, R, Nguyen, GC, Croitoru, K, Steinhart, AH & Silverberg, MS 2016, 'Higher adalimumab drug levels are associated with mucosal healing in patients with Crohn's disease', Journal of Crohn's and Colitis, vol. 10, no. 5, pp. 510-515. https://doi.org/10.1093/ecco-jcc/jjw014
Zittan, E. ; Kabakchiev, B. ; Milgrom, R. ; Nguyen, G. C. ; Croitoru, K. ; Steinhart, A. H. ; Silverberg, M. S. / Higher adalimumab drug levels are associated with mucosal healing in patients with Crohn's disease. In: Journal of Crohn's and Colitis. 2016 ; Vol. 10, No. 5. pp. 510-515.
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AU - Kabakchiev, B.

AU - Milgrom, R.

AU - Nguyen, G. C.

AU - Croitoru, K.

AU - Steinhart, A. H.

AU - Silverberg, M. S.

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N2 - Background and aims: The current approach to managing the loss of response to anti-tumour necrosis factor (TNF) agents is generally empirical. Prior studies have suggested that adalimumab levels of >4.9 μg/mL are required to achieve clinical remission. Our aim was to identify an optimal adalimumab level to achieve endoscopic healing in Crohn's disease (CD). Methods: A cohort of 60 CD patients treated with adalimumab between 2005 and 2013 were reviewed for the study. Demographic and clinical information was obtained from chart review and patient interview. Disease activity was determined using the Harvey-Bradshaw index (HBI), ileocolonoscopy reports and C-reactive protein (CRP) levels. Clinical remission was defined as HBI <5. Endoscopic remission/mucosal healing (MH) was defined as the absence of any ulceration in all ileocolonic segments. Trough adalimumab levels and adalimumab antibody levels were tested using a liquid-phase mobility shift assay. Results: Lower median CRP was significantly associated with MH 1.2mg/dl vs no MH 14.4mg/dl (p = 6.93×10-6). Higher adalimumab trough level was significantly associated with MH (median 14.7 μg/mL in those with MH vs 3.4 μg/mL in those without, p = 6.25×10-5). Higher adalimumab trough level was also significantly associated with the combined outcome of clinical and endoscopic remission (median 13.0 vs 4.8 μg/mL, p = 5.36×10-3). A cut-off of 8.14 μg/ml best discriminated subjects with MH from those without MH, with sensitivity and specificity of 91.4 and 76.0%, respectively (positive and negative predictive values 84.2 and 86.4%, respectively). Conclusions: Higher adalimumab levels were significantly associated with MH. This study suggests that attaining MH alone or a combined outcome of clinical and endoscopic remission is more likely to occur in those patients who achieve an adalimumab trough level of at least 8.14 μg/mL.

AB - Background and aims: The current approach to managing the loss of response to anti-tumour necrosis factor (TNF) agents is generally empirical. Prior studies have suggested that adalimumab levels of >4.9 μg/mL are required to achieve clinical remission. Our aim was to identify an optimal adalimumab level to achieve endoscopic healing in Crohn's disease (CD). Methods: A cohort of 60 CD patients treated with adalimumab between 2005 and 2013 were reviewed for the study. Demographic and clinical information was obtained from chart review and patient interview. Disease activity was determined using the Harvey-Bradshaw index (HBI), ileocolonoscopy reports and C-reactive protein (CRP) levels. Clinical remission was defined as HBI <5. Endoscopic remission/mucosal healing (MH) was defined as the absence of any ulceration in all ileocolonic segments. Trough adalimumab levels and adalimumab antibody levels were tested using a liquid-phase mobility shift assay. Results: Lower median CRP was significantly associated with MH 1.2mg/dl vs no MH 14.4mg/dl (p = 6.93×10-6). Higher adalimumab trough level was significantly associated with MH (median 14.7 μg/mL in those with MH vs 3.4 μg/mL in those without, p = 6.25×10-5). Higher adalimumab trough level was also significantly associated with the combined outcome of clinical and endoscopic remission (median 13.0 vs 4.8 μg/mL, p = 5.36×10-3). A cut-off of 8.14 μg/ml best discriminated subjects with MH from those without MH, with sensitivity and specificity of 91.4 and 76.0%, respectively (positive and negative predictive values 84.2 and 86.4%, respectively). Conclusions: Higher adalimumab levels were significantly associated with MH. This study suggests that attaining MH alone or a combined outcome of clinical and endoscopic remission is more likely to occur in those patients who achieve an adalimumab trough level of at least 8.14 μg/mL.

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