Key points from the evidence

The content of this evidence summary was up-to-date in June 2015. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Summary

Budesonide multimatrix (MMX, Cortiment) is a corticosteroid that is taken orally but exerts its action topically in the colon.

In two 8‑week studies, budesonide MMX statistically significantly increased rates of combined clinical and endoscopic remission in adults with mild to moderate ulcerative colitis compared with placebo. However the effect size was small and the clinical relevance of the improvements is unclear. There was no statistically significant difference between budesonide MMX and placebo for clinical improvement and endoscopic improvement at week 8 (secondary end points). It is not known how budesonide MMX compares to other treatments for ulcerative colitis. Adverse event rates were not substantially different for budesonide MMX and placebo.

Regulatory status: In October 2014, a marketing authorisation was granted for budesonide MMX for inducing remission in mild to moderate active ulcerative colitis in adults for whom aminosalicylate treatment is not sufficient.

Effectiveness

  • In 2 RCTs (n=510 and n=512), a statistically significantly higher clinical and endoscopic remission rate at week 8 was observed for budesonide MMX compared with placebo (p=0.0143 and p=0.0047).

  • There was no statistically significant difference between budesonide MMX and placebo for clinical improvement (secondary end point).

  • These studies only included people not currently taking any concomitant medication for their condition.

  • No evidence versus active comparators is published at this time.

Safety

  • The summary of product characteristics states that the most common adverse effects of budesonide MMX are nausea, upper abdominal pain, headache, insomnia, altered mood, decreased blood cortisol, influenza and viral upper respiratory tract infection.

  • The proportions of adverse events, serious adverse events and glucocorticoid adverse events seen with budesonide MMX were not substantially different from placebo in the 2 RCTs.

Patient factors

  • Alternative treatments are available for use orally and rectally, in a number of different formulations.

  • Budesonide MMX is not licensed for maintenance of remission in ulcerative colitis.

  • Other budesonide preparations (Entocort and Budenofalk) are not licensed for ulcerative colitis.

  • It is not known how budesonide MMX compares with other treatments for ulcerative colitis, alone or in combination.

Resource implications

  • Budesonide MMX costs £75.00 for 30 tablets, with an 8‑week course costing £140.

  • The cost of an 8‑week course of other commonly prescribed options ranges from around £10 to £150 for oral treatment or £30 to £500 for topical treatments (see cost table for details).

Introduction and current guidance

Ulcerative colitis is the most common type of inflammatory bowel disease, and usually affects the rectum and a variable extent of the colon proximal to the rectum.

The NICE guideline on ulcerative colitis recommends a stepped approach for inducing remission in people with mild to moderate ulcerative colitis, with choice of treatment guided by the site of inflammation. Topical or oral aminosalicylates are generally used first‑line: oral beclometasone dipropionate is an option for some people. Topical corticosteroids and oral prednisolone are options for people who cannot take or decline aminosalicylates. Combinations of treatments or immunosuppressants may be used if response to earlier treatment steps is inadequate.

Full text of introduction and current guidance.

Product overview

Cortiment is formulated to release budesonide, an oral corticosteroid, at a controlled rate throughout the colon to minimise systemic absorption. The licensed dose is 9 mg in the morning, for up to 8 weeks.

Budesonide MMX was granted a marketing authorisation in October 2014 and is licensed for inducing remission in mild to moderate active ulcerative colitis in adults for whom aminosalicylate treatment is not sufficient.

Full text of product overview.

Evidence review

  • This evidence summary is based on two 8‑week, randomised, placebo and active‑controlled phase III trials of similar design (CORE I [n= 510] and CORE II [n= 512]) that compared budesonide MMX (9 mg and 6 mg) with placebo in adults with mild to moderate ulcerative colitis (Sandborn et al. 2012 and Travis et al. 2014). Only the results for the 9 mg strength of budesonide are discussed in this evidence summary because the 6 mg dose is unlicensed.

  • Mesalazine (Asacol) and a different formulation of budesonide, which releases the drug in the ileum and ascending colon (Entocort: licensed for Crohn's disease but not ulcerative colitis), were included as active controls in CORE I and CORE II respectively. However, neither trial was designed or powered to compare the efficacy of budesonide MMX with the active treatments.

  • For the primary end point of combined clinical and endoscopic remission at week 8, budesonide MMX was statistically significantly more effective than placebo in both randomised controlled trials (RCTs). In CORE I, 17.9% of people taking budesonide MMX were in clinical and endoscopic remission at week 8, compared with 7.4% of people taking placebo (odds ratio [OR] 2.71, 95% confidence interval [CI] 1.19 to 6.16, p=0.0143). Similar results were seen in CORE II, with 17.4% of people taking budesonide MMX in clinical and endoscopic remission at week 8, compared with 4.5% of people taking placebo (OR 4.49, 95% CI 1.47 to 13.72, p=0.0047). The public assessment report for budesonide MMX notes that the clinical importance of the 10−13% improvement over placebo is questionable, although, it also notes that rather strict remission criteria were used in the studies.

  • There was no statistically significant difference in clinical improvement (secondary end point) between budesonide MMX and placebo in either trial. Because a hierarchical testing model was used and the difference between the groups in clinical improvement was not statistically significant, statistical comparisons between budesonide MMX and placebo for endoscopic improvement and other outcomes are considered exploratory only.

  • Pooled data from CORE I and CORE II showed 56.5% of people treated with budesonide MMX reported an adverse event, compared with 53.5% in the placebo group. The most common adverse events reported for budesonide MMX across CORE I and CORE II were relapse or worsening of ulcerative colitis (13.3% compared with 14.0% for placebo); headache (11.4% compared with 10.5% for placebo); nausea (5.1% compared with 4.3% for placebo); and abdominal pain (3.5% compared with 5.8% for placebo). The most common potential glucocorticoid‑related effects for budesonide MMX were mood changes (2.7% compared with 3.9% for placebo), sleep changes (2.7% compared with 4.3% for placebo), insomnia (2.4% compared with 3.1% for placebo) and acne (1.6% compared with 1.9% for placebo) (Sandborn et al. 2015).

  • A high number of people were recruited to the studies and subsequently excluded from efficacy analyses, particularly in CORE II, primarily because of normal histology results. This may have affected the statistical power of the studies to detect differences between the groups.

  • The studies were undertaken in people who were not currently taking any concomitant medication for their condition. Therefore, it is not known how well budesonide MMX works in combination with an aminosalicylate (topical or oral). It is also unclear how well budesonide MMX works in people who do not respond to aminosalicylates. A further study comparing budesonide MMX with placebo as add‑on therapy to oral aminosalicylates in people with ulcerative colitis has been undertaken but has not been fully published (the Contribute trial). Budesonide MMX has not been compared with topical corticosteroids or oral prednisolone, which are recommended second‑line options in the NICE guideline on ulcerative colitis. The studies did not report on speed of onset of budesonide MMX or the active controls.

Full text of evidence review.

Context

The 28‑day cost (excluding VAT) of Budesonide MMX 9 mg tablets is £70. The 28‑day cost (excluding VAT) of other commonly prescribed treatments for ulcerative colitis ranges from:

  • £5.16 to £52.79 for oral corticosteroids

  • £24.66 to £79.33 for oral aminosalicylates

  • £14.00 to £272.00 for topical corticosteroids and

  • £40.01 to £53.44 for topical aminosalicylates.

Full text of context.

Estimated impact for the NHS

Localities will need to take safety, efficacy, cost and patient factors into account when considering the place in therapy of budesonide MMX.

Budesonide MMX is licensed for inducing remission in mild to moderate active ulcerative colitis in adults for whom aminosalicylate treatment is not sufficient. The public assessment report concluded that treatment with budesonide MMX can be beneficial for some people and, given the limitations of the currently available treatments, presents clinicians with an additional therapeutic option. The report suggests that the role for budesonide MMX may be to induce remission of ulcerative colitis before systemic corticosteroids are tried, which are associated with more severe adverse effects. Whether budesonide MMX should be used as first- or second‑line therapy, after use of an aminosalicylate or in combination with an aminosalicylate (topical or oral) cannot be determined based on the available published evidence.

Full text of estimated impact for the NHS.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.