Complete mucosal healing of distal lesions induced by twice-daily budesonide 2-mg foam promoted clinical remission of mild-to-moderate ulcerative colitis with distal active inflammation: double-blind, randomized study

Abstract

Background: Budesonide foam is used for the topical treatment of distal ulcerative colitis. This phase III study was performed to confirm mucosal healing and other therapeutic effects of twice-daily budesonide 2-mg foam in patients with mild-to-moderate ulcerative colitis including left-sided colitis and pancolitis.

Methods: This was a multicenter, randomized, placebo-controlled, double-blind trial. A total of 126 patients with mild-to-moderate ulcerative colitis with active inflammation in the distal colon were randomized to two groups receiving twice-daily budesonide 2 mg/25 ml foam or placebo foam. The primary endpoint was the percentage of complete mucosal healing of distal lesions (endoscopic subscore of 0) at week 6. Some patients continued the treatment through week 12. Drug efficacy and safety were evaluated.

Results: The percentages of both complete mucosal healing of distal lesions and clinical remission were significantly improved in the budesonide as compared with the placebo group (p = 0.0003 and p = 0.0035). Subgroup analysis showed similar efficacy of budesonide foam for complete mucosal healing of distal lesions and clinical remission regardless of disease type. The clinical remission percentage tended to be higher in patients achieving complete mucosal healing of distal lesions than in other patients. There were no safety concerns with budesonide foam.

Conclusions: This study confirmed for the first time complete mucosal healing with twice-daily budesonide 2-mg foam in mild-to-moderate ulcerative colitis with distal active inflammation. The results also indicated that complete mucosal healing of distal lesions by budesonide foam promotes clinical remission of ulcerative colitis. Clinical trial registration no.: Japic CTI-142704.

Keywords: Budesonide foam; Mucosal healing; Ulcerative colitis.

Fig. 1

Patient flow diagram. a Initial 6-week treatment (weeks 1–6), b further 6-week continuous treatment (weeks 7–12)

Fig. 2

a Complete mucosal healing of distal lesions and clinical remission in patients with ulcerative colitis at week 6. b Complete mucosal healing of distal lesions and c clinical remission in subgroups of patients with proctitis, left-sided colitis, and pancolitis at week 6. d Clinical remission in patients who achieved complete mucosal healing of distal lesions in the budesonide group at week 6. Statistical analyses were performed at a significance level of 0.05 (two-sided). Asterisks significant difference, CI confidence interval

Fig. 3

Other subgroup analysis. a Complete mucosal healing of distal lesions. b Clinical remission. Statistical analyses were performed at a significance level of 0.05 (two-sided). High-dose 5-ASA means 4.0 g of Pentasa^® or 3.6 g of Asacol^® or 4.0 g of salazosulfapyridine. The low dose means less than these dosages or no use of oral 5-ASA. Asterisks significant difference, 5-ASA 5-aminosalicylic acid, CI confidence interval, MMDAI Modified Mayo Disease Activity Index

Fig. 4

Percentage of patients with a rectal bleeding subscore of 0 on each day. a Proctitis subgroup. b Left-sided colitis and pancolitis subgroups