Association between 6-thioguanine nucleotide levels and preventing production of antibodies to infliximab in patients with inflammatory bowel disease

Abstract

Objective Combination therapy with infliximab and a thiopurine has been shown to be more effective than monotherapy in patients with inflammatory bowel disease (IBD). The therapeutic efficacy of thiopurines is correlated with 6-thioguanine (6-TGN) levels between 235 and 450 pmol/8×108 erythrocytes. The primary aim of the study was to investigate the association between 6-TGN levels and inhibition prevention of the production of antibodies to infliximab (ATI).Design We performed a retrospective review of the medical records of patients being treated with infliximab for IBD at University Hospitals Bristol NHS Foundation Trust. Demographic and biochemical data were extracted, alongside thiopurine metabolite levels, trough levels of infliximab and the presence of ATI. χ2 tests were used to investigate the association between 6-TGN levels and prevention of ATI. Logistic regression was used to compare the odds of prevented ATI between those with a 6-TGN level between 235 and 450 pmol/8×108 erythrocytes, those with a 6-TGN level outside of this range, and the baseline group who were on infliximab monotherapy.Results Data were extracted for 100 patients. Six of 32 patients with a 6-TGN level between 235 and 450 pmol/8×108 erythrocytes developed ATI (18.8%) compared with 14 out of 22 (63.6%) patients with a 6-TGN outside of this range and 32 out of 46 (69.6%) patients on monotherapy (p=0.001). The OR (95% CI) for prevented ATI in those with a 6-TGN between 235 and 450 pmol/8×108 erythrocytes compared with a 6-TGN outside of this range was 7.6 (2.2, 26.3) (p=0.001) and compared with monotherapy was 9.9 (3.3, 29.4) (p=0.001).Conclusion 6-TGN levels between 235 and 450 pmol/8×108 erythrocytes prevented production of ATI. This supports therapeutic drug monitoring to help guide treatment and maximise the beneficial effects of combination therapy for patients with IBD.