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Maintenance Adalimumab Concentrations Are Associated with Biochemical, Endoscopic, and Histologic Remission in Inflammatory Bowel Disease

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Abstract

Background

A treat-to-target therapeutic approach is emerging as the new standard of care for treating inflammatory bowel disease (IBD), Crohn’s disease (CD), and ulcerative colitis (UC).

Aims

We aimed to investigate the association of serum adalimumab concentrations during maintenance therapy with biochemical, endoscopic, and histologic remission in IBD.

Methods

This retrospective multicenter study included consecutive IBD patients on adalimumab maintenance therapy who had a C-reactive protein (CRP) within 1 week and/or endoscopic evaluation within 12 weeks of therapeutic drug monitoring between July 2013 and December 2016. Biochemical remission was defined as a normal CRP (≤ 5 mg/L). Endoscopic remission was defined as the absence of any ulceration/erosion or a Rutgeerts score of ≤ i1 for patients with an ileocolonic resection for CD and a Mayo endoscopic score of ≤ 1 for UC. Histologic remission was defined as the absence of any sign of active inflammation. Adalimumab concentrations were measured using the homogeneous mobility shift assay.

Results

Ninety-one CRP levels and 72 colonoscopies from 98 IBD patients [CD: n = 72 (73%)] were evaluated. Based on receiver operating characteristic analyses, we identified an adalimumab concentration threshold of 11.8, 12, and 12.2 μg/mL in CD and 10.5, 16.2, and 16.2 μg/mL in UC to stratify patients with or without biochemical, endoscopic, or histologic remission, respectively. Adalimumab concentrations ≥ 12 μg/mL (OR 8; 95% CI 2–31.9; p = 0.003) and ≥ 12.2 μg/mL (OR 9.6; 95% CI 1.7–56.1; p = 0.012) were independently associated with endoscopic and histologic remission in CD, respectively.

Conclusions

This study demonstrates that higher maintenance adalimumab concentrations are associated with objective therapeutic outcomes in IBD.

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Acknowledgments

Konstantinos Papamichael is a recepient of the Ruth L. Kirschstein NRSA Institutional Research Training Grant 5T32DK007760-18. The content of this project is solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Author’s contribution

K.P. contributed to the study concept and design, data acquisition, analysis and interpretation, statistical analysis, and manuscript writing; A.J. contributed to data acquisition and interpretation and manuscript writing; B.P.V. contributed to the data acquisition and interpretation and manuscript critical revision; A.S.C contributed to study concept and design, data analysis and interpretation, and manuscript critical revision. All the authors approved the final draft.

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Author notes

  1. Anna Juncadella and Konstantinos Papamichael have equally contributed to this work.

Authors and Affiliations

  1. Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth-Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA, 02215, USA

    Anna Juncadella, Konstantinos Papamichael & Adam S. Cheifetz

  2. Department of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA

    Byron P. Vaughn

Authors
  1. Anna Juncadella
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  2. Konstantinos Papamichael
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  4. Adam S. Cheifetz
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Corresponding author

Correspondence to Konstantinos Papamichael.

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Conflict of interest

A.S.C received consultancy fees from AbbVie, Janssen, Takeda, Ferring, Miraca, AMAG, and Pfizer; B.P.V. receives research support from Takeda, Genentech, and Celgene and has received compensation from Janssen and AbbVie for speaking and advisory boards. The remaining authors disclose no conflicts of interest.

Ethical standards

All procedures performed in the study were in accordance with the International Standard of Good Clinical Practice procedures and with the principles of the Declaration of Helsinki (1964) and relevant amendments. The protocol was approved by all institutional review boards and ethics committees at participating sites.

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Juncadella, A., Papamichael, K., Vaughn, B.P. et al. Maintenance Adalimumab Concentrations Are Associated with Biochemical, Endoscopic, and Histologic Remission in Inflammatory Bowel Disease. Dig Dis Sci 63, 3067–3073 (2018). https://doi.org/10.1007/s10620-018-5202-5

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  • DOI: https://doi.org/10.1007/s10620-018-5202-5

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