Association between pharmacokinetics of adalimumab and mucosal healing in patients with inflammatory bowel diseases

Abstract

Background & aims: Little is known about the association between pharmacokinetic features of adalimumab and mucosal healing in patients with inflammatory bowel disease (IBD).

Methods: We conducted a cross-sectional study of 40 patients with Crohn's disease (CD) or ulcerative colitis (UC) who received adalimumab maintenance therapy and underwent endoscopic evaluation of disease activity and pharmacokinetic analysis (measurements of trough levels and antibodies against adalimumab). Patients in clinical remission were identified based on CD activity index scores less than 150 or Mayo scores less than 3 (for those with UC). Patients with mucosal healing were identified based on Mayo endoscopic scores less than 2 (for UC) or the disappearance of all ulcerations (for CD).

Results: The median trough level of adalimumab was higher in patients in clinical remission (6.02 μg/mL) than in patients with active disease (3.2 μg/mL; P = .012). Trough levels of adalimumab were also higher in patients with mucosal healing (6.5 μg/mL) than in patients without (4.2 μg/mL; P < .005). These results did not vary with type of IBD. On multivariate analysis, trough levels of adalimumab (relative risk, 0.62; 95% confidence interval, 0.40-0.94; P = .026) and duration of adalimumab treatment (relative risk, 0.82; 95% confidence interval, 0.68-0.97; P = .026) were associated independently with healing mucosa. An absence of mucosal healing was associated with trough levels of adalimumab less than 4.9 μg/mL (likelihood ratio, 4.3; sensitivity, 66%; specificity, 85%).

Conclusions: Trough levels of adalimumab are significantly higher in IBD patients who are in clinical remission and in those with mucosal healing. Detection of antibodies against adalimumab predicts a lack of mucosal healing.

Keywords: AAA; ADA; AUROC; Anti-Adalimumab; C-reactive protein; CD; CDAI; CRP; Crohn's Disease Activity Index; Crohn’s disease; IBD; LHR; MH; Outcome; Prognostic Factor; ROC; Response to Therapy; TNF; UC; adalimumab; antibodies against adalimumab; area under the receiver-operating characteristic curve; inflammatory bowel disease; likelihood ratio; mucosal healing; receiver-operating characteristic; tumor necrosis factor; ulcerative colitis.