Budesonide multi-matrix induces endoscopic remission in refractory UC

Last Updated: 2017-03-23

By Will Boggs MD

NEW YORK (Reuters Health) - Budesonide multi-matrix induces remission in patients with mild to moderate mesalamine-refractory ulcerative colitis (UC), researchers report.

"While we were not surprised by the primary endpoint being significantly better than placebo, I was intrigued by the endoscopic and histologic healing results, which showed quite nice and objective disease improvement,” said Dr. David T. Rubin from the University of Chicago Medicine.

“This bodes well for patients who respond to this therapy, as we know that endoscopic and histologic outcomes correlate with better short- and long-term results,” he told Reuters Health by email.

Budesonide is a second-generation corticosteroid, and the multi-matrix extended-release tablets were developed to pass intact through the stomach and release active drug throughout the length of the colon.

Dr. Rubin and colleagues evaluated budesonide multi-matrix 9 mg given once daily for eight weeks for the induction of remission of mild to moderate UC not adequately controlled by oral mesalamine (5-ASA) therapy.

Of the 510 randomized patients, 230 assigned to budesonide and 228 assigned to placebo were included in the modified intent-to-treat population; 85% and 93%, respectively, completed the study.

Significantly more budesonide-treated patients than placebo patients achieved combined clinical and endoscopic remission after eight weeks (13% vs. 7.5%, p=0.049), the researchers report in the Journal of Crohn's and Colitis, online March 4.

Similar percentages of patients receiving budesonide (24.3%) and placebo (22.8%) achieved clinical remission, but significantly more patients treated with budesonide (20.0%) than with placebo (12.3%) achieved endoscopic remission (p=0.025).

Histologic healing was significantly more common in the budesonide group than in the placebo group (27% vs. 17.5%, p=0.016), although the groups did not differ in the exploratory endpoint of percentage of patients with clinical improvement at week eight.

Inflammatory bowel disease-related quality of life improved by week two and was maintained through week eight in both groups.

Potential glucocorticoid-related adverse events were more common in patients treated with budesonide (9.0%) than in those treated with placebo (5.9%).

Mean morning plasma cortisol concentrations remained within normal levels in both treatment groups, but mean cortisol concentrations after ACTH stimulation were below normal with budesonide after eight weeks.

“The reason we performed this study was because the original pivotal trials of this therapy didn't provide information about where it was most likely to be positioned, in combination with 5-ASA or specifically after 5-ASA therapy failed,” Dr. Rubin said. “This answers that and suggests that it might be best positioned before systemic steroids (prednisone) and after a trial of 5-ASA first.”

Santarus, Inc., previously a wholly owned subsidiary of Salix Pharmaceuticals, funded the trial. Four of the 10 authors were employed by Salix when the analysis was done; Dr. Rubin and several co-authors reported financial relationships with the companies.

SOURCE: http://bit.ly/2mvSuRA

J Crohns Colitis 2017.