Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: A meta-analysis

Background & Aims: 6-Thioguanine nucleotide (6-TGN) levels have been proposed to correlate with inflammatory bowel disease (IBD) activity among patients treated with azathioprine or 6-mercaptopurine (6-MP). Previous studies, most with small sample sizes, yielded conflicting conclusions. Our aim was to pool the available data to provide a more precise estimate of the association between 6-TGN levels and IBD activity. Methods: We searched Medline and PubMed (from :1966 to November 2004) and reviewed the reference lists of selected articles. Fixed and random-effects models were used to test whether mean/median 6-TGN levels differed among patients with active disease vs remission and whether 6-TGN levels above a threshold of 230 -260 pmol/8 x 10(8) red blood cells were associated with clinical remission. When studies reported multiple 6-TGN threshold values, we used the data for the lower value. Results: We identified 55 articles, 12 of which contained data sufficient for inclusion. The mean/median 6-TGN levels were higher among patients in remission than in those with active IBD) (pooled difference, 66 pmol/8 X 10(8) red blood cells; 95% confidence interval, 18-113; P =.006), but with significant heterogeneity. Excluding the 1 outlier study eliminated this heterogeneity. Patients with 6-TGN levels above the threshold value were more likely to be in remission (62%) than those below the threshold value (36%) (pooled odds ratio, 3.3; 95% confidence interval, 1.7-6.3; P <.001), but with significant heterogeneity. Again, excluding the I outlier study eliminated this heterogeneity. Conclusions: Although prior studies yielded inconsistent conclusions, this analysis strongly supports that higher 6-TGN levels are associated with clinical remission.