Pharmacokinetics of adalimumab in inflammatory bowel diseases: a systematic review and meta-analysis.
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.
*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.
Stephane
S
Paul
Amelie Carla
AC
Moreau
Emilie
E
Del Tedesco
Melanie
M
Rinaudo
Jean-Marc
JM
Phelip
Christian
C
Genin
Laurent
L
Peyrin-Biroulet
Xavier
X
Roblin
D000068879:Adalimumab; D000328:Adult; D000367:Age Factors; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy; D003424:Crohn Disease / Q000175:diagnosis / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008991:Monitoring, Physiologic; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D000068879:Adalimumab