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.

• Authors: Uri Kopylov, Robert Battat, Amine Benmassaoud, Laurence Paradis-Surprenant, Ernest G Seidman
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 60 Issue 2 Pg. 478-84 (Feb 2015) ISSN: 1573-2568 [Electronic] United States
• PMID: 25236422 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Biomarkers
• Guanine Nucleotides
• Hemoglobins
• Thionucleotides
• 6-thioguanylic acid
• 6-methylthiopurine
• Mercaptopurine
• Azathioprine

Topics

• Anti-Inflammatory Agents (blood, therapeutic use)
• Azathioprine (blood, therapeutic use)
• Biomarkers (blood)
• Colitis, Ulcerative (blood, diagnosis, drug therapy)
• Crohn Disease (blood, diagnosis, drug therapy)
• Cross-Sectional Studies
• Drug Monitoring (methods)
• Erythrocyte Indices
• Female
• Guanine Nucleotides (blood)
• Hematologic Tests
• Hemoglobins (metabolism)
• Humans
• Lymphocyte Count
• Male
• Mercaptopurine (analogs & derivatives, blood, therapeutic use)
• Platelet Count
• Predictive Value of Tests
• Retrospective Studies
• Thionucleotides (blood)
• Treatment Outcome