Both topical and oral 5-ASA medications have been shown to be effective for the maintenance of remission of L-UC [1, 6]. Often, topical 5-ASA therapy can be tapered during maintenance therapy. Studies have found that mesalamine enemas can maintain remission if used on an every other day or every third day schedule [1]. In a meta-analysis, 5-ASA enemas (4 g) had maintenance of remission rates of 78 %, slightly decreasing to 72 % for every other night dosing, and 65 % for every third night dosing, with no statistical difference being found between dosing intervals [9, 13]. The main difficulty with this approach is patient acceptance of long-term rectally administered therapy. In addition, topical 5-ASA at a dose of as low as 1 g daily has been shown to be effective as a maintenance therapy [6]. Additional studies have demonstrated 1-year remission rates of 52–92 %, with no differences being found between 2 and 4 g doses of rectal 5-ASA, which parallels findings from the induction studies [40].

In general, a dose of 2.4 g/day of oral 5-ASA has been shown to be effective for maintenance therapy. Maintenance rates ranged from 60 to 92 % for the various oral formulations, with no apparent dose response [9]. However, if patients require corticosteroids or higher doses of 5-ASA to induce remission, it is the authors’ opinion that they may benefit from higher maintenance doses. If patients required combination therapy to induce remission, both medications should be continued during the maintenance phase.

Finally, studies have compared rectal and oral 5-ASA formulations for the maintenance of remission of L-UC. Mantzaris et al. compared every third night 5-ASA enemas to 1.5 g/day oral 5-ASA (thrice daily divided dosing) [56]. At 2 years, remission was maintained in 75 % of the patients in the enema group, compared to only 32 % of the oral 5-ASA group (p < 0.001). Topical 5-ASA maintenance therapy was found to be more efficacious than oral 5-ASA therapy, up to a 24-month end point, in a meta-analysis [7]. This meta-analysis included 3 studies comparing rectal and oral 5-ASA for the maintenance of remission of L-UC, with durations of therapy from 6 to 24 months. The POR for the maintenance of remission was 2.3 (1.1–4.8) in favor of topical therapy.

Finally, combination maintenance therapy utilizing rectal and oral 5-ASA formulations has been evaluated. D’Albasio et al. randomized 60 patients to receive either 4 g 5-ASA enema for the first 7 days each month or sulfasalazine (2 g daily) [57]. At a 2-year end point, there was no difference in relapse rate between the two groups. The same authors then randomized 72 patients to receive 1.6 g daily oral 5-ASA combined with twice weekly 5-ASA enemas (4 g) or oral 5-ASA plus a placebo enema [58]. The 1-year relapse rate in the combination therapy group was significantly less than in the monotherapy group (39 % vs. 69 %, p < 0.036).

For the maintenance of remission of L-UC, rectal 5-ASA therapy is superior to placebo and at least as efficacious as oral 5-ASA. In addition, oral and rectal combination maintenance therapy may be superior to either therapy alone.

Multiple studies have shown corticosteroids to be an ineffective maintenance therapy for the maintenance of remission of UC [1, 6, 13]. In addition, these medications are associated with multiple well-described side effects, including hospitalization and mortality [59]. A randomized trial of oral corticosteroid maintenance therapy compared to placebo, for a treatment duration of 6 months, did not find any difference in remission rates, with approximately 40 % of each group being in remission [60]. Lindgren et al.’s study of different dosages of budesonide enemas included a maintenance phase to determine relapse rates [19]. By week 24, 40–50 % of patients in the corticosteroid enema group had experienced disease relapse, depending on dosing strategy. Clinical guidelines recommend against the use of corticosteroids for maintenance therapy in patients with UC, and the use of these medications should be limited due to their significant side effects and lack of efficacy [1, 6, 46].

For patients who cannot maintain remission with 5-ASA medications alone, either topical or oral, or who have corticosteroid-dependent disease, treatment should be escalated to an immunomodulator or biologic agent [1, 13]. As discussed above, corticosteroids are not effective for the maintenance of remission, and steroid-sparing medications are indicated for patients with moderate-to-severe disease that requires systemic corticosteroids to achieve remission.

Though there is not extensive data to support the effectiveness of immunomodulators for the treatment of active UC, these medications may be effective steroid-sparing maintenance medications [13, 61, 62]. Thiopurine therapy has been found to be superior to placebo in the maintenance of remission of UC, though there have been no comparative studies specifically evaluating these medications specifically in patients with L-UC [55, 62]. Studies have demonstrated the maintenance of remission rates for immunomodulators of approximately 65 % over 1 year, for UC [13]. In steroid-dependent UC patients, azathioprine was found to lead to higher rates of clinical and endoscopic remissions, as well as steroid cessation, compared to patients randomized to receive oral 5-ASA. However, at least four double-blind, randomized, placebo-controlled studies did not demonstrate benefit of azathioprine therapy compared to placebo in patients with steroid-dependent UC [13]. Finally, infliximab can be used for the maintenance of remission of L-UC, though there are few studies with follow-up past 52 weeks [1]. However, some guidelines do not recommend infliximab maintenance therapy for UC due to low corticosteroid-free remission rates after 1 year [6].

Treatment options for the maintenance of remission of L-UC depend on the medication that was able to successfully induce remission. If remission was induced by a rectal or oral 5-ASA, these medications can be continued indefinitely, either as monotherapy or in combination. If compliance with rectal therapy is problematic, enema dosing for maintenance therapy can be recommended on an every other or every third night schedule. If topical corticosteroids were used to induce remission, therapy should be switched to a rectal and/or oral 5-ASA. If patients experience disease relapse on 5-ASA maintenance therapy, they should be treated as recommended in the induction of remission algorithm (Fig. 22.1). With disease relapse, special attention should be given to assessing for alternative causes of symptoms, including infection, noncompliance, etc.

Patients who require either oral or especially intravenous corticosteroids to achieve remission often require immunomodulator or biologic agents in order to maintain remission. However, it is worthwhile attempting treatment with maximum 5-ASA therapy prior to escalating therapy to an immunomodulator. In these cases, oral 5-ASA should be given in a dose of 4.8 g daily, and patients should also receive concomitant topical 5-ASA therapy. If patients relapse following an attempt at 5-ASA therapy and require an additional oral corticosteroid course, immunomodulators should be initiated and continued long term. Further treatment recommendations in these cases parallel those for extensive UC.