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P585. Association between thiopurines metabolites levels and clinical remission in IBD patients: an updated meta-analysis

A. Moreau1, S. Laporte1, E. Del Tedesco1, M. Rinaudo-Gaujous1, J.M. Phelip1, S. Paul1, X. Roblin1, 1University of Saint Etienne, Saint Etienne, France

Background

A first meta-analysis, published in 2006, support the association between thiopurines metabolites levels (6-thioguanine nucleotides or 6-TGN) and clinical remission. This meta-analysis has pooled the results of 6 studies (N = 518 patients). Since then, several studies have been published and some of them present conflicting conclusions. Therefore, an update of this first meta-analysis has been performed.

Methods

A systematic search was performed up to July 2012. The primary goal was to assess the association between thiopurines metabolites levels and clinical remission in IBD patients. Secondary objectives were to evaluate whether or not the association was influenced by differences in study design such as the presence of a selection and/or information bias (misclassification by differences in disease activity scores, metabolites concentration assays). A Mantel–Haenszel pooled risk estimate provided a measure of that association. The Cochran Q test and the I2 statistic were used to evaluate heterogeneity between studies. Two different softwares were used for all statistical analysis (Revman® and R).

Results

A total of 20 studies were included in this meta-analysis (N = 2405 patients). When studying datas with a cut-off level of 230 pmol / 8.108 RBC (N = 2234 patients), the pooled OR was 2.09 (95% CI, 1.53–2.87, p < 0.00001). Visual inspection of funnel plot asymmetry and statistical asymmetry tests were also performed. Neither showed indication of publication bias. A sensitivity analysis was conducted and showed no significant difference in the overall OR with removal of any individual study (Figure 1).

Figure 1.

Conclusion

This meta-analysis reasserts the utility of using cut-off levels of thiopurines metabolites for the monitoring of IBD patients. The results of the cumulative meta-analysis are univocals and representative: the OR stabilizes with time and it clearly demonstrates the inutility to perform any more studies to establish the association between thiopurines metabolites levels and clinical remission in IBD patients.

1. Osterman MT (2006), Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta analysis. Gastroenterology.