Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial

Abstract

ObjectiveThis 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis.DesignA 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.ResultsClinical 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. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious.ConclusionsBudesonide 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 numbershttp://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31).

Aquaporins in Infection and Inflammation

“…The only effective treatment for MC is the glucocorticoid budesonide [213]. Budesonide treatment induces clinical remission in around 80% of patients and improves stool consistency and passage frequency rapidly [214]. Since stool consistency has been shown to be the main determinant for impaired QOL [215], budesonide treatment has a great impact on the patient's everyday life.…”

Letter: the definition of budesonide dependence in microscopic colitis—authors’ reply

“…We also agree with their clinically important recommendation that maintenance budesonide should be used at the lowest effective dose, to minimise the risk of steroid-related side effects and cost, as noted in reviews from the USA and Europe. 3,4 An average dose of 4.5 mg/d was more effective than placebo in a randomised trial, 5 and in clinical practice, doses as low as 3 mg/d or even 3 mg every other day may be effective for maintenance. The Spanish Microscopic Colitis Group demonstrated the effectiveness of this strategy in a group of patients with collagenous colitis, and also reported that a subset of patients requires higher doses.…”

Diagnostic Algorithm and Treatment for Microscopic Colitis: A Review.

“…A low dose of oral budesonide (4.5 mg/day) given as maintenance therapy was also effective for maintaining clinical remission over a 12-month period in 61.4% of the patients with CC in an RCT, but 82.1% of patients who received budesonide during the 12 months relapsed during the treatment-free follow-up (Münch et al 2016). There was a high-relapse rate after discontinuation 82.1% (23/28 patients) (Münch et al 2016). Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all of which were non-serious (Münch et al 2016).…”

“…There was a high-relapse rate after discontinuation 82.1% (23/28 patients) (Münch et al 2016). Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all of which were non-serious (Münch et al 2016). Risk factors associated with relapse included high-stool frequency at baseline and a long duration of diarrhea (O'Toole 2016).…”

“…It is required to make a review of the patient's medication list, including over-the-counter products, to identify drugs or other substances that might cause MC or worsen diarrhea (Table 1) After withdrawal of budesonide, between 61% and 88% of patients experience clinical relapse (Münch et al 2016). A low dose of oral budesonide (4.5 mg/day) given as maintenance therapy was also effective for maintaining clinical remission over a 12-month period in 61.4% of the patients with CC in an RCT, but 82.1% of patients who received budesonide during the 12 months relapsed during the treatment-free follow-up (Münch et al 2016). There was a high-relapse rate after discontinuation 82.1% (23/28 patients) (Münch et al 2016).…”