Association Between Pharmacokinetics of Adalimumab and Mucosal Healing in Patients With Inflammatory Bowel Diseases
Résumé
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.
Mots clés
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