Gut 2016;65:47-56 doi:10.1136/gutjnl-2014-308363
Inflammatory bowel disease
Original article
Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial
Open Access
Andreas Münch1, Johan Bohr2, Stephan Miehlke3, Cecilia Benoni4, Martin Olesen5, Åke Öst6, Lars Strandberg7, Per M Hellström8, Erik Hertervig9, Peter Armerding10, Jiri Stehlik11, Greger Lindberg12, Jan Björk13, Annika Lapidus14, Robert Löfberg15, Ole Bonderup16, Sören Avnström17, Martin Rössle18, Karin Dilger19, Ralph Mueller19, Roland Greinwald19, Curt Tysk2, Magnus Ström1 on behalf of the BUC-63 investigators
+ Author Affiliations
Objective This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis.
Design A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase.
Results Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. [
b]During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. [/b]Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious.
Conclusions Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation.
Trial registration numbers
http://www.clinicaltrials.gov (NCT01278082) and
http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31).
Significance of this study
Significance of this study
What is already known on this subject?
Collagenous colitis, a presentation of microscopic colitis, is associated with severely impaired health-related quality of life.
Oral budesonide at a dose of 9 mg/day for 6–8 weeks induces remission in 77%–100% of patients with collagenous colitis.
After withdrawal of budesonide, between 61% and 88% of patients experience clinical relapse but long-term data on budesonide maintenance therapy, and on the use of low-dose budesonide, are lacking.
What are the new findings?
In a prospective, randomised, placebo-controlled trial of low-dose oral budesonide therapy (mean dose 4.5 mg/day) in patients with collagenous colitis, clinical remission was maintained to 1 year in 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (p<0.001).
Health-related quality of life was maintained to 1 year with low-dose oral budesonide.
Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all of which were non-serious.
How might it impact on clinical practice in the foreseeable future?
Maintenance therapy with low-dose budesonide (mean 4.5 mg/day) appears beneficial and safe in patients with collagenous colitis who have achieved clinical remission under standard budesonide therapy and reduces the high relapse rate observed after budesonide discontinuation.