The cornerstone for induction and maintenance of remission in mild to moderate ulcerative colitis is 5-ASA agents which are thought to act by activating nuclear receptors that influence inflammation, cell proliferation, apoptosis, and the metabolic function of colonic epithelial cells [1]. In active proctitis, the therapy is targeted directly to the rectum with mesalamine suppositories which have been found to be more effective than oral 5-ASA formulations showing remission as early as 2 weeks in a meta-analysis comparing the two forms of delivery (oral vs. topical) [2]. This medication is usually given in a dose of 500 mg twice daily or 1 g daily and is considered safe, well tolerated, and effective in patients with active proctitis and distal colitis [3, 4]. The selection for the type of topical therapy is dependent on the extent of involvement with suppositories reaching 10–15 cm and foams reaching 15–20 cm, while enemas may reach up to the splenic flexure. Disadvantages include bloating and leaking which may lead to noncompliance. Topical corticosteroids are also used to assist in induction of remission but are not effective in maintenance [2, 5]. However, topical steroids have been found to be as effective as systemic corticosteroids with significantly lower inhibition of cortisol levels for patients with left-sided colitis [6]. At times, complete response is not obtained with topical therapy alone. In these instances, oral mesalamine may be added to the regimen as it has been found to provide quicker and more complete relief of rectal symptoms than oral or rectal formulations used alone [7].

As in patients experiencing difficulty controlling active proctitis, combination therapy is more effective than monotherapy for induction of remission. In a randomized double-blinded study, oral mesalamine in combination with mesalamine enemas induced remission in 64 % of patients within 8 weeks compared to 43 % of patients taking oral mesalamine with a placebo [8]. There is, however, a dose-related effect of oral 5-ASA therapy. The ASCEND III trial, a non-inferiority study, found that 70 % of the 389 patients receiving delayed-release mesalamine 4.8 g daily achieved treatment success at 6 weeks compared to 66 % of those receiving a dose of 2.4 g daily. However, significantly more patients who received 4.8 g daily achieved clinical remission at weeks 3 and 6 compared to those receiving 2.4 g daily [9]. In the ASCEND I trial, a statistically significant difference in treatment success was found in a subgroup of patients with moderate active colitis receiving delayed-release mesalamine at 4.8 g compared to those receiving 2.4 g, 72 % and 57 %, respectively [10]. Patients with moderate disease benefit the most from higher doses when considering balance of side effect profile to therapeutic response.

In general 5-ASAs are affordable and well tolerated; however, some patients experience nausea, vomiting, dyspepsia, headache, and anorexia in varying degrees making full compliance with this medication difficult. More severe reactions including pancreatitis, hepatotoxicity, bone marrow suppression, interstitial nephritis, and anemia have also been found. Additionally, 5-ASAs specifically sulfasalazine can affect sperm morphology which is reversible when discontinued [5]. In 1–2 % of the population, 5-ASA therapy can cause worsening of ulcerative colitis and should be discontinued in this group.