Individually administered or co-prescribed thiopurines and mesalamines for inflammatory bowel disease

Abstract

Data from both basic research and clinical experience continue to suggest that mesalamines and thiopurines are effective and efficient for the maintenance of remission of inflammatory bowel diseases. Several decades following the formalization of their indications, attention on these two drugs has been fostered by recent achievements. Demonstration of the ability of mesalamine to activate a colonocyte differentiation factor has shed light on its chemopreventive effects on colorectal cancer; in addition to their anti-proliferative efficacy, thiopurines have been shown to be specific regulators of apoptosis. The two drugs are often co-administered in clinical practice. Recent advancements have shown that mesalamines exert a positive synergism in this context, insofar as they can inhibit side-methylation of thiopurines and hasten the function of the main immunosuppressive pathways. Considering that up to 40% of patients cannot tolerate thiopurines, such renovated targets have stimulated efforts to improve compliance by research on the toxicity mechanisms. The definition of genetic polymorphisms in the enzymes of thiopurine metabolism, and the uncovering of synergistic drug interactions, such as that with allopurinol, are just two of the results of such efforts. Interaction between basic research and clinical practice has continued to inform indications and refine the prescriptions of mesalamines and thiopurines; these have not been restrained (they have been implemented in some cases) by the advent of the novel biological molecules with anti-cytokine activity.

Monitoring thiopurine metabolites in inflammatory bowel disease

“…Combination of AZA or MP with aminosalicylates is very common in clinical practice 61. Many studies have found that aminosalicylates increase 6TGN levels in a majority of the patients, although whether or not this increase has clinical significance still remains controversial.…”

Update 2014

“…89,90 Addition of 5-ASA to thiopurine therapy led to increase in total 6-TGN levels in 82% of study patients in 1 study and 100% in another study. 89,90 Addition of 5-ASA to thiopurine therapy led to increase in total 6-TGN levels in 82% of study patients in 1 study and 100% in another study.…”

The Pharmacogenetic Basis of Individual Variation in Thiopurine Metabolism

“…Several studies indicate that 5-ASAs may influence the metabolism of thiopurines [106][107][108][109]. This is important, as 71% of patients with IBD established on thiopurines are coprescribed 5-ASAs [109].…”

“…Several studies indicate that 5-ASAs may influence the metabolism of thiopurines [106][107][108][109]. This is important, as 71% of patients with IBD established on thiopurines are coprescribed 5-ASAs [109]. A recent retro spective ana lysis has shown that administration of concomitant 5-ASA (3 g/day mesalazine) leads to significantly higher TGN levels in comparison with patients prescribed AZA/MP alone, and is a risk factor for myelotoxicity (odds ratio: 3.45; 95% CI: 1.31-9.04; p = 0.01) [110].…”