Budesonide for Ulcerative Colitis: Perhaps a Future First-line Agent

Budesonide MMX Versus Placebo in Patients with Active, Mild-to-Moderate Ulcerative Colitis Who Were 5-ASA Naïve or Previously Treated with 5-ASA: A Poster Session at AIBD 2013 Presenter: Gary Lichtenstein, MD, FACG, AGAF, University of Pennsylvania, Philadelphia

Budesonide MMX was approved in the United States for use in ulcerative colitis (UC) in January of 2013. It is a novel oral preparation of an existing corticosteroid-its tablet, coated with a film that dissolves only after exposure to a pH of 7 or higher, remains intact until it reaches the colon, sharply limiting systemic absorption until it reaches its target.

The corticosteroid is suspended in a pill matrix that expands after the film dissolves, forming a hydrogel that delivers an extended release of budesonide directly to the colonic mucosa. Absorbed budesonide is subject to high first-pass metabolism, minimizing corticosteroid adverse effects.

The CORE I and CORE II studies established efficacy of budesonide MMX in 2 randomized, double-blind, placebo-controlled studies of a total of 899 adult patients with active, mild-to-moderate UC. Current guidelines recommend that this cohort of patients with UC receive initial therapy with mesalamine (5-ASA), escalating to treatment with systemic corticosteroids, azathioprine, and 6-mercaptopurine, and biologic agents if durable remission is not achieved.

5-ASA is a terrific choice-if it works. Unfortunately, many patients do not achieve lasting remission on 5-ASA-the number-needed-to-treat (NNT) to achieve 1 remission is 5.

In patients who fail standard-dose 5-ASA, the NNT with high-dose therapy to achieve remission in a nonresponder to standard-dose therapy is 25. Not terribly impressive, and our patients (and all of us) worry about early escalation to more aggressive disease-modifying agents because of justified concerns about malignancy and life-threatening infection.

The original CORE studies demonstrated the efficacy of budesonide MMX. However, they did not report on outcome differences in 5-ASA–naïve patients versus patients previously treated with 5-ASA.

This poster session summarized a new post-hoc analysis of CORE I/CORE II data (442 patients), comparing the efficacy of budesonide MMX in 2 groups of patients with mild-to-moderate UC, in the following ways:

• Budesonide-MMX was their first-line agent (5-ASA naïve): odds ratio of remission compared with placebo, 6.7; NNT (to achieve remission), 7.

• Previously treated with 5-ASA and failed, then received budesonide-MMX: odds ratio of remission compared with placebo, 2.6; NNT (to achieve remission), 11.

Treatment-related adverse effects occurred with equal frequency in both cohorts. The authors concluded that budesonide-MMX was well-tolerated and effective in both cohorts and that it should be considered as a future first-line agent in mild-to-moderate UC.

Although budesonide is clearly more effective in patients who have not already failed 5-ASA, these data suggest it may be worth a try-before moving on to potentially more dangerous drugs. That said, it’s clearly not a game-changer-the NNT data show that most patients who embark on this strategy will need to escalate.