Oral corticosteroids are effective for the induction of remission in patients with moderate to severe ulcerative colitis [38], in milder disease that is refractory to sulfasalazine or mesalazine, and in patients who have responded to initial treatment with intravenous corticosteroids following hospitalization for acute severe disease. Prednisone and prednisolone are well absorbed after oral administration, with a high bioavailability (over 70 %). Absorption may be delayed, however, in patients with severe ulcerative colitis [39]. Although a daily dose of 40 mg prednisolone is more effective than 20 mg, doses above this threshold have not demonstrated incremental benefit, but are associated with increased adverse effects [40]. Single daily dosing is as effective as split-dosing and causes less adrenal suppression [41]. Both clinical and endoscopic response can be seen following 2 weeks of treatment with oral prednisolone [12, 20]. Those who have not responded by then are considered to have corticosteroid-refractory disease and should be treated with anti-tumor necrosis factor (anti-TNF) therapy , tacrolimus or intravenous corticosteroid therapy [42]. The optimal tapering regimen has not been determined but the dose is usually reduced over 8–12 weeks.

Topical corticosteroids are effective therapy for left-sided ulcerative colitis, with second-generation formulations (budesonide and beclomethasone dipropionate enemas) showing similar efficacies to topical mesalazine [51, 52]. Corticosteroids absorbed from the rectum (as opposed to the proximal gastrointestinal tract) do not undergo first-pass metabolism in the liver, and can result in adrenal suppression [53]. Studies of systemic bioavailability of topical corticosteroids in healthy subjects show high variability: from 2 % to 90 % of hydrocortisone administered as an enema was available systemically [54, 55]. The presence of rectal inflammation may reduce systemic absorption [56].

In active left-sided ulcerative colitis, budesonide enemas (2 mg, once a day) have shown similar endoscopic, histological and clinical response rates compared to both hydrocortisone foam (125 mg, once a day) and prednisolone (31.25 mg, once a day) enemas, but without the significant reduction in plasma cortisol levels seen with hydrocortisone [57] and prednisolone [58]. Beclomethasone dipropionate enemas (3 mg, once a day) also had a similar response compared with prednisolone enemas, again without the reduction in cortisol levels seen with prednisolone [28]. Budesonide foam enemas are better tolerated than budesonide liquid enemas and are just as effective [59].

The optimum dose of corticosteroid for acute severe ulcerative colitis has not been established. However, hydrocortisone 300–400 mg intravenously every 24 h (or equivalent) is recommended based on clinical trial data, with an overall response rate of 67 % [60]. Again, higher doses are no more effective and lower doses are less effective. Therapy extending beyond 7–10 days provides no additional benefit [60]. The response to intravenous corticosteroids should be assessed objectively at day 3 to determine those who might need salvage therapy with ciclosporin or infliximab [61]. Predictors of poor response to medical therapy, with the need for early colectomy, include clinical markers (stool frequency), biochemical markers (elevated CRP, low albumin), radiological signs (colonic dilatation or mucosal islands on plain X-ray), and endoscopic appearance (severe ulceration) [62].

Although they are effective agents for induction of remission of active ulcerative colitis, corticosteroids are not beneficial in maintaining remission [63–65]. Short courses (<3 weeks) and low starting doses (<15 mg prednisolone ) of oral corticosteroids are associated with early relapse [40]. It is recommended that corticosteroids are tapered over several weeks, first to avoid rapid relapse, secondly, to allow the introduction or optimization of mesalazine, immunomodulators (thiopurines or methotrexate ), and biological therapy, and thirdly, to allow resumption of usual function of the hypothalamic–pituitary–adrenal axis. The most favorable regimen for corticosteroid tapering has not been determined, but a standardized taper can identify early those who are corticosteroid-dependent [66]. Arthralgia and myalgia can occur as corticosteroids are tapered. This usually responds to paracetamol and reassurance, but improvement can take several months and some patients need reintroduction of corticosteroids with a slower taper [67].

Up to one-third of patients with ulcerative colitis fail to respond to standard courses of corticosteroid therapy and have corticosteroid-resistant disease [61, 68]. This may be due to a superimposed pathogen, such as cytomegalovirus infection or Clostridium difficile toxin, which should be excluded. An association between glucocorticoid receptor polymorphisms and corticosteroid resistance in IBD has been postulated, but a meta-analysis of five studies involving 942 cases was underpowered to detect this [69].

Corticosteroid resistance may occur downstream in the glucocorticoid receptor-signaling pathway via inflammatory cytokines. Tumor necrosis factor α (TNF-α) decreases corticosteroid sensitivity in monocytes by downregulation of the glucocorticoid receptor [70], and in patients with ulcerative colitis, mucosal levels of this inflammatory cytokine, along with IL-6 and IL-8, are higher in corticosteroid-resistant patients [71]. Infliximab, a TNF-α blocker, is effective for corticosteroid-resistant disease [72], as too are the calcineurin inhibitors, ciclosporin and tacrolimus [73, 74]. Calcineurin participates in the synthesis of interleukin-2 (IL-2), which has been implicated in the development of corticosteroid-resistant T lymphocytes. However, a trial of basiliximab, a monoclonal antibody that binds to and blocks CD25 on activated T lymphocytes, inhibiting IL-2 binding and IL-2 mediated proliferation, did not show an increased effectiveness of corticosteroids for induction of remission in outpatients with moderate to severe, steroid-resistant ulcerative colitis [75].