Aminosalicylates in inflammatory bowel disease

Abstract

SUMMARYAminosalicylate therapy for ulcerative colitis remains a foundational strategy for the induction and maintenance of remission for mild to moderate disease. Although it seems clear that topical mesalazine (mesalamine) is the most efficacious approach to distal ulcerative colitis, recent trials with orally delivered azo conjugates suggest that there may be an advantage over pH-released mesalazine as a first-line approach to active disease. No such comparisons are available for azo products and the prolonged-release formulation, Pentasa. However, recent meta-analyses have demonstrated that, although there is little difference in systemic exposure between marketed products, luminal concentrations may vary. In maintenance therapy, aminosalicylates remain the standard approach after aminosalicylate-induced remission. A number of gaps remain in the evidence base with regard to the optimal dosing of oral mesalazine as a maintenance agent, whether oral mesalazine can maintain remissions after rectal mesalazine induction, and the dose-response and efficacy of aminosalicylates after steroid-or ciclosporininduced remissions. Although aminosalicylates have been advocated for several decades in Crohn's disease, a number of controversies have evolved since the original trials with sulfasalazine in active Crohn's disease. The original trials demonstrated benefits for sulfasalazine in colonic involvement, but controlled trial evidence for the role of sulfasalazine as maintenance therapy has not been as firmly established. In addition, although oral mesalazine has been demonstrated in controlled trials to be superior to placebo in mild to moderate disease, it is less efficacious than corticosteroids at inducing remissions. The maintenance benefits of mesalazine appear to be limited to patients Ôinduced into remissionÕ with mesalazine and in some post-operative settings.

Clinical trial: oral prednisolone metasulfobenzoate (Predocol) vs. oral prednisolone for active ulcerative colitis

“…26 It has recently been clearly established that the epithelial cell is the predominant and possibly only target cell for mesalazine in UC, 27 but the differential effects of systemic and topical corticosteroids suggest that this may not be the principal target for corticosteroids, even when topically administered. The efficacy demonstrated in this study with a corticosteroid that shows minimal systemic effect does, however, suggest that the steroid target cells, at least in patients who do not have severe colitis, are present within the mucosa.…”

“…At 6 months, remission rates were 51% for Predocol 40 mg ⁄ day, 38% for Predocol 60 mg ⁄ day and 32% for tapering prednisolone (P = 0.08). [25][26][27]; h tapering prednisolone ⁄ placebo (n = 38-39). P-values reflect the adjusted mean treatment differences using analysis of covariance.…”

Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults

“…Remission rate for budesonide was 69% vs 62% for 5ASA [61] . These data have to compare with a previous metaanalysis which showed 5ASA no more effective than placebo [62] . The minimal efficient dose is 4 g/d.…”

Polysaccharides for Colon–Targeted Drug Delivery: Improved Drug–Release Specificity and Therapeutic Benefits

“…Also, pH differences between the distal ileum, cecum and proximal colon are small. Therefore, it is difficult to determine exactly where in the gastrointestinal tract the 5-ASA will be released (Hanauer, 2004 (Sandborn, 2006b;Caprilli et al, 2009) The time-controlled release system uses a microsphere of ethylcellulose to coat the 5-ASA. The microsphere swells and dissolves slowly as the drug moves through the gastrointestinal tract, releasing the 5-ASA mainly in the duodenum and proximal colon (Rasmussen et al, 1982).…”