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Association Between Pharmacokinetics of Adalimumab and Mucosal Healing in Patients With Inflammatory Bowel Diseases

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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.

Section snippets

Patients

We conducted a cross-sectional study including all patients with CD or UC receiving ADA maintenance therapy and undergoing routine endoscopy (evaluation of disease activity or screening for dysplasia). Evaluation of endoscopic disease activity (X.R. and E.D.T), and therapeutic drug monitoring of ADA between June 2011 and June 2012 were analyzed. This was a prospective observational study enrolling patients treated at Saint-Etienne University Hospital. The total Mayo score for UC and the Crohn's

Results

A total of 40 IBD patients could be analyzed. Patient characteristics are reported in Table 1. The mean age of the patients was 42.7 years with a sex ratio (male:female) of 0.8. The mean ADA duration was 10.7 months and the median CRP level was 14 mg/mL (16 mg/mL (range, 7–18) for CD and 12 mg/mL (range, 3–20) for UC). A total of 22 patients had CD: 31% of them were in clinical remission (N = 7) and 36% had MH (N = 8). Eighteen patients had UC and 33% were in clinical remission (N = 6), and 44%

Discussion

This study investigated the association between mucosal healing and therapeutic drug monitoring of ADA in patients with IBD. There is growing evidence that therapeutic drug monitoring of anti-TNF agents (infliximab, ADA) is associated with clinical outcomes.

In a recent meta-analysis, the presence of antibodies to infliximab was associated with a significantly higher risk of loss of clinical response to infliximab and lower serum infliximab levels in patients with IBD.13

In a

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Conflicts of interest These authors disclose the following: Laurent Peyrin–Biroulet has received lecture and consulting fees from Abbvie and MSD, and Xavier Roblin has received lecture and consulting fees from Merck. The remaining authors disclose no conflicts.

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