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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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.
- Anti-TNF therapy
- Antibodies to adalimumab
- Crohn’s disease
- Therapeutic drug monitoring
- Ulcerative colitis