Hematologic indices as surrogate markers for monitoring thiopurine therapy in IBD

Abstract

Background: Clinical efficacy and risk of complications are associated with intracellular levels of thiopurine metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurines (6-MMP) in patients with Crohn's disease. Therapeutic monitoring of thiopurine metabolites is not widely available. Surrogate markers such as hematologic indices (MCV, leukopenia) have been proposed.

Aims: To evaluate accuracy of hematologic indices for prediction of therapeutic levels of thiopurine metabolites.

Methods: A retrospective cross-sectional study. We included patients treated with thiopurines for IBD between February 2008 and November 2013. Hematologic indices were correlated with thiopurine metabolites and compared to pre-treatment levels.

Results: A total of 168 patients with 608 measurements were included. Macrocytosis was observed in 4.5 % of the patients. On multivariate analysis, macrocytosis was associated with 6-TGN levels >235 pmol/8 × 10(8) erythrocytes and 6-mmp levels >5,700 pmol/8 × 10(8) erythrocytes. Therapeutic 6-TGN levels were associated with MCV, ΔMCV, macrocytosis and lymphocyte count. Sensitivity and Spearman's r correlation for prediction of therapeutic metabolite levels were poor for all hematologic indices.

Conclusion: Although macrocytosis and an elevated MCV are associated with therapeutic 6-TGN levels, the correlation is weak. None of the evaluated hematologic indices is a reliable surrogate marker for thiopurine metabolite levels.