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WASHINGTON -- Once-daily budesonide in gastro-resistant capsule form (Budenofalk) showed promise as an oral treatment for lymphocytic colitis, a manufacturer-sponsored phase III study demonstrated.

At week 8, clinical remission was seen in 78.9% of patients randomized to budesonide capsules, 9 mg/day, compared with only 42.1% of those given placebo (P=0.01), reported Stephan Miehlke, MD, of the Center for Digestive Diseases, Internal Medicine Center, in Hamburg, Germany.

In contrast, a statistically significant difference from placebo was not seen among patients receiving mesalazine granules (Salofalk), 3 g/day, with clinical remission being observed in 63.2% of patients (P=0.09), he said at here.

"Lymphocytic colitis is a histologic subtype of microscopic colitis and is a common cause of chronic nonbloody diarrhea," Miehlke explained. Symptoms not only include diarrhea but also abdominal pain, fecal incontinence, and nocturnal diarrhea. "Due to this symptom burden, this is a socially disabling disease associated with substantial declines in quality of life."

Budenofalk is approved in Great Britain and elsewhere for acute treatment of Crohn's disease and collageneous colitis attacks as well as autoimmune hepatitis. Small studies have suggested that oral budesonide is useful for lymphocytic colitis but further randomized trials have been called for. Mesalazine has been considered a potential second-line therapy, but has never been tested in a placebo-controlled trial.

Accordingly, Miehlke and colleagues recruited 57 patients in whom they performed colonoscopy before and after 8 weeks of treatment. Participants were required to have had symptoms for at least 12 weeks and at least 28 stools within the week before baseline, and the histological diagnosis was confirmed by a central pathologist.

Clinical remission was defined as no more than 21 stools in the 7 days prior to the 8-week endpoint with no more than six watery stools.

The majority of patients were women whose mean age was 60. The duration of the current flare was approximately 4 months, and disease activity was considered moderate.

The time to remission was rapid with budesonide, at a median of 3 days compared with 12 days for mesalazine and 21 days for placebo, with the difference between budesonide and placebo being significant (P=0.044). The difference between mesalazine and placebo did not reach statistical significance.

On quality-of-life measures, budesonide again was superior. For symptom burden, the change from baseline at week 8 was -42 for the budesonide group, -36 for the mesalazine group, and -21 for the placebo group, while the changes for general well-being were -28, -14, and -14, respectively.

Histologic remission was achieved by 69% of patients receiving budesonide, 26% of the mesalazine group, and 21% of the placebo group, with a highly significant difference between budesonide and placebo (P=0.008), Miehlke reported.

The treatment was well tolerated, with no difference between budesonide and placebo. Serious adverse events were reported in 10% of both active treatment groups and in 5% of the placebo group.

"We conclude that budesonide 9 mg/day is highly effective for the induction of clinical and histological remission, not only reducing stool frequency but also improving patients' quality of life," he said. "Mesalazine in dosages of 3 g/day was not statistically significantly better than placebo in this trial, and appeared to be less effective than budesonide."

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