Immune modifiers have a slower onset of action (typically, a 2- to 3-month lag) and, consequently, are not used for induction of remission. However, these agents have shown effectiveness for their steroid-sparing action in persons with refractory disease; they are also used as primary treatment for fistulas and maintenance of remission in patients intolerant of or not responsive to aminosalicylates.

The immunomodulators 6-mercaptopurine (6-MP) and azathioprine (AZA) are used in patients with inflammatory bowel disease (IBD) in whom remission is difficult to maintain with the aminosalicylates alone. Calcineurin inhibitors such as cyclosporin A (CSA) and tacrolimus, as well as methotrexate (MTX), are also immune-modifying agents^[3] ; CSA is almost exclusively limited to acute severe colitis, whereas tacrolimus has been used in both perianal Crohn disease and ulcerative colitis.^[3]

Data on MTX support the use of intramuscular MTX in Crohn disease, but such data are lacking in ulcerative colitis. The only trial of MTX in ulcerative colitis used a low-dose oral therapy^[91] ; whether a higher-dose oral MTX or parenteral MTX (IM or SQ) may be effective in ulcerative colitis has not been studied. Several clinical trials showed that AZA continuation in patients with ulcerative colitis prevented relapse, as compared to those who discontinued the medication. However, other trials have shown trends but no statistically significant benefit of AZA in ulcerative colitis.^[92]

^{http://emedicine.medscape.com/article/179037-treatment#d14}