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Pharmacokinetics of Adalimumab in Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis

Paul, Stephane PhD*; Moreau, Amelie Carla PhD*; Del Tedesco, Emilie MD; Rinaudo, Melanie MD, PhD*; Phelip, Jean-Marc MD, PhD; Genin, Christian MD, PhD*; Peyrin-Biroulet, Laurent MD, PhD; Roblin, Xavier MD, PhD

doi: 10.1097/MIB.0000000000000037
Clinical Review Articles

Background: The aim of this meta-analysis was to explore the magnitude of the association between pharmacokinetics of adalimumab and clinical response in patients with inflammatory bowel disease.

Methods: A literature search was performed up to December 2013. MEDLINE, EMBASE, Cochrane, and meeting abstracts were reviewed. Studies were included if they analyzed the association of trough levels of adalimumab (TRA) or antibodies against adalimumab (AAA) with clinical response in adult or pediatric inflammatory bowel disease. A Mantel–Haenszel pooled risk estimate provided a measure of the association.

Results: Fourteen studies enrolling 1941 patients with inflammatory bowel disease were included in the systematic review. Thirteen studies analyzed clinical outcomes according to TRA. In only 1 study, there was no correlation between high TRA and clinical response. Six of the 7 studies reported a negative correlation between AAA and clinical outcomes. Six studies enrolling 536 patients (Crohn's disease [CD] only) met the meta-analysis inclusion criteria. The pooled odds ratio (OR) for loss of clinical response to adalimumab in patients with CD (N = 4) with positive AAAs was 10.15 (95% confidence interval [CI]: 3.90–26.40, P < 0.0001). Patients with CD with TRA over a predefined cutoff were more likely to be in clinical remission with an OR of 2.6 (95% CI: 1.79–3.77, P < 0.0001). The association was stronger if the analysis was limited to the adult population (N = 3, OR: 7.05, 95% CI: 3.58–13.9, P < 0.0001).

Conclusions: The presence of AAA is associated with a higher risk of loss of clinical response to adalimumab, whereas high TRA is associated with greater clinical response rates in CD. More data are needed in ulcerative colitis.

Article first published online 14 May 2014.

*Laboratoire d'Immunologie et d'Immunomonitoring, CHU de Saint-Etienne, Saint-Etienne, France;

Service de Gastrologie-Entérologie-Hépatologie, CHU de Saint-Etienne, Saint-Etienne, France; and

Department of Gastroenterology, Inserm U954, University Hospital of Nancy, Université de Lorraine, Nancy, France.

Reprints: Xavier Roblin, MD, PhD, Department of Gastroenterology, CHU de Saint-Etienne, Avenue Albert Raymond, Saint-Etienne 42023, France (e-mail:

L. Peyrin-Biroulet received Lecture and/or consulting fees from MSD, Abbvie, UCB-pharma, and X. Roblin received Lecture and consulting fees from Merck, Abbvie, and Theradiag. The remaining authors have no conflicts of interest to disclose.

Received February 01, 2014

Accepted February 27, 2014

© Crohn's & Colitis Foundation of America, Inc.
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