Treatment of Ulcerative Colitis

Wojciech Blonski; Anna M. Buchner; Gary R. Lichtenstein

Disclosures

Curr Opin Gastroenterol. 2014;30(1):84-96. 

In This Article

Systemic Corticosteroids

Conventional corticosteroids (e.g. prednisone) should be introduced in patients who do not have adequate response within 10–14 days to oral and topical 5-ASA formulations or in clinical scenarios when rapid improvement needs to be achieved.[15]

Over the years, treatment with oral corticosteroids (prednisone) has been shown to be the most effective in inducing remission within an average of 7–14 days when given at a daily dose of 40–60 mg.[16–18]

In spite of the lack of randomized trials evaluating the steroid taper schedules, the general consensus calls for tapering 5–10 mg weekly after achieving remission until a dose of 20 mg is reached[18] and then below a dose of 20 mg 2.5–5.0 mg per week..[18] In the hospital settings, treatment of severe ulcerative colitis flare ups requires the use of intravenous steroids such as methylprednisolone 60 mg/day or hydrocortisone 300 mg/day. The natural history of therapy with oral prednisone (40–60 mg daily) or intravenous corticosteroids with tapering over 3–6 months was evaluated in a population-based, inception cohort study from Olmsted County, Minnesota, USA.[19] Within the first month of therapy, it was noted that 54% of patients with ulcerative colitis were in complete remission, 30% were in partial remission and 16% did not respond to the treatment.[19] There was an evidence of prolonged outcome over 1-year period with prolonged response rate of 49%, steroid dependency rate of 22% and a colectomy rate of 29%.[19] Treatment with intravenous corticosteroids for 5–14 days resulted in response rates in 45–80% of patients.[20–23]

The overall efficacy of glucocorticosteroids in active disease was evaluated in a recent meta-analysis of five RCTs comparing the efficacy of glucocorticosteroids with placebo.[24]

Remission rates with active treatment in individual trials varied from 13 to 80% and the likelihood of not achieving remission was significantly lower with glucocorticosteroids [relative risk (RR) 0.65, 95% confidence interval (CI) 0.45–0.93], with a number needed to treat of 3. In addition, there was evidence of adverse events of glucocorticosteroids such as infections, weight gain, hyperglycemia, acne, hirsutism and hypertension. Bone loss occurs within the first 6 months of treatment and warrants supplementation with calcium and vitamin D.

Systemic corticosteroids are not effective as therapy for maintenance of remission in ulcerative colitis and therefore should not be recommended for maintenance therapy. Their efficacy was either comparable to that of placebo[25,26] or the rate of corticosteroids related adverse events was higher than that of placebo despite superiority in maintaining remission.[27]

In view of the significant side-effect profile associated with the use of systemic corticosteroids, there have been trials of treatment with oral budesonide, a corticosteroid with high topical activity and much lower profile of adverse events. An initial Cochrane meta-analysis of RCTs of oral budesonide in inducing clinical remission of ulcerative colitis determined that treatment with this agent had significantly lower efficacy than oral mesalamine (RR = 0.72, 95% CI 0.57–0.91) given for 8 weeks and was equally effective to placebo (RR = 1.41, 95% CI 0.59–3.39) given for 4 weeks.[28] Since then, colonic release of budesonide (budesonide MMX) has been introduced and recently evaluated in the randomized double-blind double-dummy placebo controlled CORE I trial of 509 patients.[29] Based on this trial, once-daily oral budesonide MMX was determined to be well tolerated and more effective than placebo in inducing remission in patients with active mild-to-moderate ulcerative colitis and the rates of remission at week 8 among subjects given budesonide MMX or mesalamine were 19.9% and 12.1%, respectively compared with 7.5% placebo. Furthermore, in the randomized Core II study, budesonide MMX 9 mg provided a statistically significant increase in the combined clinical and endoscopic remission rate compared with placebo (17.5 vs. 4.5%; P = 0.0047).[30]

These results are important and demonstrate that budesonide MMX is an effective therapy for achieving remission in patients with mild-to-moderate ulcerative colitis.

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