Association of 6-Thioguanine Nucleotide Levels and Inflammatory Bowel Disease Activity: A Meta-Analysis

Abstract

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. 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. 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 1 outlier study eliminated this heterogeneity. Although prior studies yielded inconsistent conclusions, this analysis strongly supports that higher 6-TGN levels are associated with clinical remission.