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A Systematic Review and Meta-Analysis of 6-Thioguanine Nucleotide Levels and Clinical Remission in Inflammatory Bowel Disease

2017; Oxford University Press; Volume: 11; Issue: 11 Linguagem: Inglês

10.1093/ecco-jcc/jjx089

1876-4479

María Manuela Estevinho, Joana Afonso, Isadora Rosa, Paula Lago, Eunice Trindade, L Correia, Cláudia Camila Dias, Fernando Magro,

Immunodeficiency and Autoimmune Disorders

Thiopurines are widely used in the management of inflammatory bowel diseases. However, their minimum effective dose and dose-response relationship remain undefined, and evidence about their use in clinical practice is mostly heterogeneous. This systematic review and meta-analysis aimed: i] to assess the clinical value of 6-thioguanine nucleotide thresholds; and ii] to compare mean 6-thioguanine nucleotide concentrations between patients in clinical remission vs. those with active disease.A systematic literature search was carried out using four databases. Statistical heterogeneity was assessed with the I2 statistic followed by subgroup and sensitivity analyses. Odds ratios were computed using the random-effects model.A total of 1384 records were identified in the systematic search, of which 25 were retained for further analysis: 22 were used in the cut-off comparisons and 12 were used in the 6-thioguanine nucleotide mean differences analysis. The global odds ratio for remission in patients with 6-thioguanine nucleotide levels above the predefined thresholds was 3.95 (95% confidence interval [CI], 2.63-5.94; p < 0.001]. When considering the different thresholds individually, the odd ratios were significant for values above 235 pmol/8 × 108 and 250 pmol/8 × 108 red blood cells [2.25 and 4.71, respectively]. Mean 6-thioguanine nucleotide levels were higher among patients in clinical remission, with a pooled difference of 63.37 pmol/8 × 108 red blood cells [95% CI, 31.81-94.93; p < 0.001].This study reinforces the link between 6-thioguanine nucleotide levels and clinical remission in inflammatory bowel diseases, also exploring the validity of specific 6-thioguanine nucleotide thresholds to predict clinical outcomes.