Maintenance Adalimumab Concentrations Are Associated with Biochemical, Endoscopic, and Histologic Remission in Inflammatory Bowel Disease
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).
We aimed to investigate the association of serum adalimumab concentrations during maintenance therapy with biochemical, endoscopic, and histologic remission in IBD.
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.
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.
This study demonstrates that higher maintenance adalimumab concentrations are associated with objective therapeutic outcomes in IBD.
KeywordsAnti-TNF therapy Crohn’s disease Ulcerative colitis Antibodies to adalimumab Therapeutic drug monitoring
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.
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.
Compliance with ethical standards
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.
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.