Ulcerative traditionally been used as an add-on therapy

Ulcerative colitis (UC) is the commonest inflammatory disease of the colon affecting close to 150,000
people in the UK1. The cause of the condition is unknown and its severity can vary, but it presents
with symptoms including abdominal pain, sudden urge to defecate and bloody diarrhoea. The
current NICE guidance for the induction of remission in episodes of mild-to-moderate UC
recommends the use of topical and/or oral preparations of a 5-aminosalicylic acid (5-ASA), such as
mesalazine, as the first-line therapy1. However, systematic review shows that no more than 60% of
patients achieve remission with mesalazine alone2. In such cases a tapering dose of oral
prednisolone has traditionally been used as an add-on therapy due to its efficacy in achieving
remission3. However, up to 90% of patients experience side effects associated with their use
including changes in body shape, mood changes, and insomnia4.

Second-generation oral corticosteroids including fluticasone dipropionate, prednisolone
metasulphobenzoate and budesonide have been developed which use novel drug-delivery
technologies to target steroids to the distal small bowel and colon5,6,7,8,9. Whilst these therapies
exhibit a potent anti-inflammatory effect they have low systemic bioavailability due to extensive
first-pass metabolism by the liver8. It has therefore been hoped that these steroids might have
similar efficacy to systemic corticosteroids with fewer adverse effects5. Whilst trials showed that the
second-generation oral corticosteroids fluticasone dipropionate and prednisolone
metasulfobenzoate had fewer side effects than prednisolone they were also less effective in
achieving remission6,7,8.

Budesonide is a potent corticosteroid which undergoes 90% first-pass metabolism in the liver9,10. A
pH-dependent-release formulation of budesonide is recommended as an alternative to conventional
corticosteroids in the management of Crohn’s disease11,12; but due to its local release pattern within
the ileum it is less effective than prednisolone in UC10. Studies from the mid-90s showed budesonide
to be as effective as prednisolone when both were given as an enema but patients often find this an
unacceptable treatment modality13,14,15. By contrast, the oral therapy Budesonide-MMX uses a multi-
matrix system to release budesonide within the colon itself which may represent a more suitable
treatment for UC16,17. A 2010 pilot study suggested that an 8-week course of Budesonide-MMX may
be more effective than placebo with a similar safety profile but the study had a small sample size
(36) and a high dropout rate (22%)18.

Two large, phase 3 trials, CORE-I and CORE-II, demonstrated that an 8-week course of Budesonide-
MMX 9mg once daily is more effective at inducing remission in mild-to-moderate UC than
placebo19,20,21. However, these studies lacked the statistical power to show greater efficacy than oral
mesalazine and only studied patients who were not taking concomitant oral mesalazine therapy. In

clinical practice steroids are more useful as an add-on to 5-ASA therapy3. Pooled safety-analysis of
the CORE-I and CORE-II studies indicate that Budesonide-MMX has a similar safety profile to placebo
and oral mesalazine22. There are currently no studies which compare the efficacy of Budesonide-
MMX with conventional corticosteroids such as prednisolone in the treatment of mild-to-moderate
UC; this represents an important gap in our knowledge that this study would fill.