Journal
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
Volume 46, Issue 3, Pages 310-318Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/00365521.2010.536254
Keywords
Crohn's disease; inflammatory bowel disease; infliximab; TNF; ulcerative colitis
Categories
Funding
- Aase and Ejnar Danielsen's Foundation
- Beckett Foundation
- Danish Biotechnology Program
- Danish Colitis-Crohn Society
- Danish Medical Association
- Frode V. Nyegaard and wife's Foundation
- Health Science Research Foundation of Region of Copenhagen
- Herlev Hospital Research Council
- Lundbeck Foundation
- P. Carl Petersens Fund
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Introduction. Reasons for infliximab failure in Crohn's disease and ulcerative colitis are debated. Serum levels of infliximab and anti-infliximab antibodies have been associated with loss of response. We aimed at determining cut-off levels for infliximab and anti-infliximab antibody concentrations associated with clinical response to infliximab maintenance therapy. Methods. Patients with inflammatory bowel disease (n == 106) were retrospectively classified as having maintained response or loss of response to infliximab maintenance therapy. Trough concentrations were measured by fluid-phase radioimmunoassays. Results. Infliximab levels were significantly lower, and anti-infliximab antibody levels significantly higher, in Crohn's disease patients with loss of response (median infliximab 0 mu mu g/ml, median anti-infliximab antibodies 35 U/ml) compared to patients with maintained response (median infliximab 2.8 mu mu g/ml, median anti-infliximab antibodies 0 U/ml; p < 0.0001). Receiver operating characteristic (ROC) analysis identified optimal cut-off values: infliximab < 0.5 mu mu g/ml, which was associated with loss of response with sensitivity 86% [64--97] and specificity 85% [72--94]; and anti-infliximab antibodies >= a parts per thousand yen10 U/ml yielding a sensitivity of 81% [61--93] and specificity 90% [79--96]. Combined measurements of infliximab and anti-infliximab antibodies using these cut-off values had higher accuracy yielding a sensitivity of 81% [57--94] and specificity 94% [82--98]. Similar pattern was observed in a smaller cohort of patients with ulcerative colitis. Conclusions. Combined measurements of infliximab and anti-infliximab antibodies using cut-off levels provided high accuracy for discriminating between clinical response types to infliximab maintenance therapy. Cut-off levels are considered a prerequisite to further investigations of clinical usefulness of measurements of infliximab and anti-infliximab antibodies in patients failing infliximab therapy.
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