These data suggest it may be worth a try-before moving on to potentially more dangerous drugs.
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.
Clinical Tips for Using Antibiotics and Corticosteroids in IBD
January 5th 2013The goals of therapy for patients with inflammatory bowel disorder include inducing and maintaining a steroid-free remission, preventing and treating the complications of the disease, minimizing treatment toxicity, achieving mucosal healing, and enhancing quality of life.