When the acute attack is controlled, a maintenance regimen is usually required, especially in patients with severe, extensive, or relapsing disease. Sulfasalazine, olsalazine, or mesalamine are all effective in reducing relapses. As a rule, patients should not be treated chronically with steroids. Azathioprine or 6-MP may be useful as steroid-sparing agents for steroid-dependent patients, and for maintenance of remission not adequately sustained by aminosalicylates, and occasionally for patients who are steroid-refractory but not acutely ill.
Sulfasalazine reduces relapse rates in UC in a dose-related fashion, with benefits demonstrated at 2-4 g/day    . Although the 4 g/day regimen is the most effective in preventing relapse, up to one-quarter of patients cannot tolerate the side effects at this dose, thus limiting its overall utility  . The newer aminosalicylate preparations–including olsalazine   , mesalamine         , and balsalazide (not yet available in the United States  –have relapse-prevention properties virtually the same as, but not more than, those of equivalent doses of sulfasalazine   . Because of the well-documented efficacy of sulfasalazine in relapse prevention, all 5-aminosalicylic acid (5-ASA) relapse-prevention trials except one  have used sulfasalazine as the control            . As with sulfasalazine, most     , if not all   , dose-ranging studies of mesalamine have demonstrated increasing efficacy with increasing doses up to 4 g/day of 5-ASA. However, unlike sulfasalazine, use of larger doses of 5-ASA in the newer preparations are generally well tolerated, lending these analogues an advantage over sulfasalazine for relapse prevention. On the other hand, the cost of sulfasalazine, especially when considered for long-term use, is considerably lower. Although the maximum length of remission-maintenance benefit has not been established, most experts recommend permanent maintenance; however, the patient with a mild first episode may opt for being followed without long-term medical maintenance therapy.
The immunomodulators azathioprine and 6-MP, have been studied for relapse prevention. In patients whose remission was achieved with azathioprine, continuation of active drug reduced the 12-month relapse rate to 36%, compared with 59% on placebo  . Similarly, recent uncontrolled retrospective data from 105 patients appear to confirm the efficacy of continued long-term 6-MP in maintaining remissions of ulcerative colitis  . However, the risk-benefit ratio of indefinite azathioprine or 6-MP use, especially when compared with colectomy, for the maintenance of remission, is not known.