A Systematic Review and Meta-Analysis of 6-Thioguanine Nucleotide Levels and Clinical Remission in Inflammatory Bowel Disease. (30th June 2017)

• Record Type: Journal Article
• Authors: Estevinho, Maria Manuela; Afonso, Joana; Rosa, Isadora; Lago, Paula; Trindade, Eunice; Correia, Luís; Dias, Cláudia Camila; Magro, Fernando
• Is Part Of: Journal of Crohn's and colitis. Volume 11:Number 11(2017:Nov.)
• Page Start: 1381
• Page End: 1392
• Publication Date: 2017-06-30
• Subjects: Thiopurines -- inflammatory bowel disease -- clinical outcome; Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjx089
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background and Aims: 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. Methods: A systematic literature search was carried out using four databases. Statistical heterogeneity was assessed with the I 2 statistic followed by subgroup and sensitivity analyses. Odds ratios were computed using the random-effects model. Results: 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 × 10 8 and 250 pmol/8 × 10 8 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 × 10 8 red blood cells [95% CI, 31.81–94.93; p < 0.001]. Conclusions: 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.