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

Andreas Münch, Johan Bohr, Stephan Miehlke, Cecilia Benoni, Martin Olesen, Åke Öst, Lars Strandberg, Per M Hellström, Erik Hertervig, Peter Armerding, Jiri Stehlik, Greger Lindberg, Jan Björk, Annika Lapidus, Robert Löfberg, Ole Bonderup, Sören Avnström, Martin Rössle, Karin Dilger, Ralph Mueller, Roland Greinwald, Curt Tysk, Magnus Ström, BUC-63 investigators, F J Baert, D J S De Wulf, J Decaestecker, M Lukas, M Bortlik, V Komárek, N Machková, J Stehlik, I Přibylová, M Pořízová, E Machytka, P Klvana, P Svoboda, O K Bonderup, H Glerup, S Avnstrøm, C Kirsch, P Armerding, S Schubert, M Rössle, S Miehlke, A Münch, M Ström, H Hjortswang, A Brinkberg Lapidus, C Lindberg, D Ståhlberg, M Danelius, R Rajani, C Grännö, H Stjernman, L Ockander, J Björk, R Befrits, J Bohr, C Tysk, E Salén, A Gustavsson, J Halfvarson, N Nyhlin, C Benoni, L Vigren, J Persson, D Klintman, E Hertervig, B Sternby, G Lindberg, L-A Bark, Y Taha, R Löfberg, P M Hellström, F Rorsman, A Lindgren, A Lasson, H Strid, L Strandberg, A Salim, Andreas Münch, Johan Bohr, Stephan Miehlke, Cecilia Benoni, Martin Olesen, Åke Öst, Lars Strandberg, Per M Hellström, Erik Hertervig, Peter Armerding, Jiri Stehlik, Greger Lindberg, Jan Björk, Annika Lapidus, Robert Löfberg, Ole Bonderup, Sören Avnström, Martin Rössle, Karin Dilger, Ralph Mueller, Roland Greinwald, Curt Tysk, Magnus Ström, BUC-63 investigators, F J Baert, D J S De Wulf, J Decaestecker, M Lukas, M Bortlik, V Komárek, N Machková, J Stehlik, I Přibylová, M Pořízová, E Machytka, P Klvana, P Svoboda, O K Bonderup, H Glerup, S Avnstrøm, C Kirsch, P Armerding, S Schubert, M Rössle, S Miehlke, A Münch, M Ström, H Hjortswang, A Brinkberg Lapidus, C Lindberg, D Ståhlberg, M Danelius, R Rajani, C Grännö, H Stjernman, L Ockander, J Björk, R Befrits, J Bohr, C Tysk, E Salén, A Gustavsson, J Halfvarson, N Nyhlin, C Benoni, L Vigren, J Persson, D Klintman, E Hertervig, B Sternby, G Lindberg, L-A Bark, Y Taha, R Löfberg, P M Hellström, F Rorsman, A Lindgren, A Lasson, H Strid, L Strandberg, A Salim

Abstract

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. 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.

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).

Keywords: MICROSCOPIC COLITIS; QUALITY OF LIFE.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Patient disposition. ITT, intent-to-treat; PP, per-protocol.
Figure 3
Figure 3
(A) Short Health Scale (SHS) dimension scores (left) and Psychological General Well-Being Index (PGWBI) global scores (right) for the open-label phase of the study during budesonide therapy. (B) SHS dimension scores in the double-blind phase of the study according to treatment group (left) and in the subpopulations of patients randomised to budesonide who did or did not remain in remission throughout the double-blind phase (right). Data are shown as median (IQRs) at the first visit and the last visit (last observation carried forward, LOCF) of each phase. The SHS Questionnaire uses 100 mm Visual Analogue Scales, with higher scores indicating lower quality of life. The PGWBI global score is standardised to a score between 0 and 100, with lower scores indicating lower quality of life.
Figure 4
Figure 4
Proportion of patients remaining in clinical remission at the end of the 12-month double-blind phase in the intent-to-treat population. Remission was defined as a mean of

Figure 5

Time to relapse during (A)…

Figure 5

Time to relapse during (A) double-blind treatment phase and (B) untreated follow-up phase…

Figure 5
Time to relapse during (A) double-blind treatment phase and (B) untreated follow-up phase (intent-to-treat population) (Kaplan–Meier estimates). Relapse was defined as a mean of ≥3 stools/day, including a mean of ≥1 watery stool/day. Circles represent censoring of patients who discontinued the study or completed their final study visit without relapse.
Figure 5
Figure 5
Time to relapse during (A) double-blind treatment phase and (B) untreated follow-up phase (intent-to-treat population) (Kaplan–Meier estimates). Relapse was defined as a mean of ≥3 stools/day, including a mean of ≥1 watery stool/day. Circles represent censoring of patients who discontinued the study or completed their final study visit without relapse.

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Source: PubMed

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