Review Article: Increasing the Dose of Oral Mesalazine Therapy for Active Ulcerative Colitis Does not Improve Remission Rates

A. V. Safdi; R. D. Cohen


Aliment Pharmacol Ther. 2007;26(9):1179-1186. 

In This Article

Summary and Introduction


Background: Oral mesalazine (mesalamine, 5-aminosalicylic acid) formulations are effective in the treatment of active ulcerative colitis. All formulations contain the same active drug but differ with regard to mechanisms to deliver the drug to the colon. Patients who fail to respond to initial therapy are often administered higher doses of the same formulation.
Aim: To review published trials of oral mesalazine formulations in treating active ulcerative colitis and to examine the effect of dose escalation on remission rates.
Results: Increasing the doses of oral mesalazine formulations does not result in higher remission rates, although increasing the doses of some formulations has been effective in increasing symptomatic improvement and/or response to treatment.
Conclusions: Because oral mesalazine formulations do not demonstrate a significant dose response with regard to induction of remission of active ulcerative colitis, simple dose escalation may not be the most effective course for patients who fail to respond to initial mesalazine treatment.


Mesalazine (mesalamine), or 5-aminosalicylic acid (5-ASA), is an effective therapy for the induction and maintenance of remission in patients with ulcerative colitis (UC),[1,2] a chronic inflammatory disease of the colonic mucosa. Because the drug acts topically, the goal of therapy is to maximize 5-ASA delivery to the colon.[3] However, because 5-ASA is readily absorbed by the upper gastrointestinal (GI) tract, various strategies have been developed to delay 5-ASA release until the drug reaches the colon. Although all oral 5-ASA formulations contain the same active drug, mechanisms to deliver the drug directly to the colon differ. These differences in drug delivery may account for variability in efficacy and tolerability among different formulations.[4,5,6]

Oral 5-ASA formulations available in the United States include controlled-release capsules[7] (Pentasa; Shire US Inc, Wayne, PA, USA), which release 5-ASA slowly throughout the length of the GI tract; pH-dependent delayed-release tablets[8] (Asacol; Procter & Gamble Pharmaceuticals Inc, Cincinnati, OH, USA) and multimatrix mesalazine tablets[9] (Lialda; Shire US Inc), both of which employ an enteric coating that dissolves when sustained pH reaches 7 or higher in the terminal ileum and colon; and azo-bonded prodrugs, in which bacterial azoreduction in the colon releases 5-ASA from a carrier molecule (Figure 1). Azo-bonded 5-ASA prodrugs include sulfasalazine (Azulfidine; Pfizer Inc, New York, NY, USA and generics), in which 5-ASA is bonded to a sulfa moiety; olsalazine (Dipentum; Pfizer Inc), which consists of two 5-ASA molecules bonded together; and balsalazide[10] (Colazal; Salix Pharmaceuticals Inc, Morrisville, NC, USA), which utilizes the inert carrier molecule 4-aminobenzoyl-ß-alanine.

Figure 1.

Mesalazine, or 5-aminosalicylic acid (5-ASA), is readily absorbed by the gastrointestinal (GI) tract, so strategies have been developed to delay drug release until the agent reaches the colon. Controlled-release mesalazine (1) releases 5-ASA slowly throughout the GI tract, where 20% to 30% of the dose is absorbed before reaching the colon.[7] pH-dependent mesalazine formulations (2) rely on an enteric coating that dissolves when pH levels reach 7 or higher in the terminal ileum, and 21% to 28% of the 5-ASA dose is absorbed prior to reaching the colon.[8,9] Azo-bonded 5-ASA prodrugs (3) rely on anaerobic bacteria in the colon to enzymatically release active drug and deliver 99% of the dose directly to the colon.[10]

Oral 5-ASA formulations are effective first-line treatments for active, mild-to-moderate UC, but many patients fail to achieve remission following initial 5-ASA therapy, and as a consequence, have their 5-ASA doses increased.[11] However, dose escalation of many formulations increases the potential for systemic absorption of 5-ASA without a clear or consistent benefit in efficacy. Because oral 5-ASA formulations differ in mechanism of drug delivery, switching unresponsive patients to another formulation may be an alternative to simply increasing the dose.[12] This article will review published clinical trials evaluating the efficacy of increasing the 5-ASA dose of each oral formulation in treating active UC.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.