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/
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References
- Münch A, Aust D, Bohr J, et al. . Microscopic colitis: current status, present and future challenges: statements of the European Microscopic Colitis Group. J Crohns Colitis 2012;6:932–45.
- Hjortswang H, Tysk C, Bohr J, et al. . Health-related quality of life is impaired in active collagenous colitis. Dig Liver Dis 2011;43:102–9.
- Baert F, Schmit A, D'Haens G, et al. . Budesonide in collagenous colitis: a double-blind placebo-controlled trial with histologic follow-up. Gastroenterology 2002;122:20–5.
- Bonderup OK, Hansen JB, Birket-Smith L, et al. . Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis. Gut 2003;52:248–51.
- Bonderup OK, Hansen JB, Teglbjaerg PS, et al. . Long-term budesonide treatment of collagenous colitis: a randomised, double-blind, placebo-controlled trial. Gut 2009;58:68–72.
- Miehlke S, Heymer P, Bethke B, et al. . Budesonide treatment for collagenous colitis: a randomized, double-blind, placebo-controlled, multicenter trial. Gastroenterology 2002;123:978–4.
- Miehlke S, Madisch A, Bethke B, et al. . Oral budesonide for maintenance treatment of collagenous colitis: a randomized, double-blind, placebo-controlled trial. Gastroenterology 2008;135:1510–16.
- Miehlke S, Madisch A, Kupcinskas L, et al. . Budesonide is more effective than mesalamine or placebo in short-term treatment of collagenous colitis. Gastroenterology 2014;146:1222–30.e2.
- Stewart MJ, Seow CH, Storr MA. Prednisolone and budesonide for short- and long-term treatment of microscopic colitis: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2011;9:881–90.
- Miehlke S, Madisch A, Voss C, et al. . Long-term follow-up of collagenous colitis after induction of clinical remission with budesonide. Aliment Pharmacol Ther 2005;22:1115–19.
- Miehlke S, Hansen JB, Madisch A, et al. . Risk factors for symptom relapse in collagenous colitis after withdrawal of short-term budesonide therapy. Inflamm Bowel Dis 2013;19:2763–7.
- Hjortswang H, Tysk C, Bohr J, et al. . Defining clinical criteria for remission and disease activity in collagenous colitis. Inflamm Bowel Dis 2009;15:1875–81.
- Hjortswang H, Jarnerot G, Curman B, et al. . The Short Health Scale: a valid measure of subjective health in ulcerative colitis. Scand J Gastroenterol 2006;41: 1196–203.
- Dupuy HJ. The Psychological General Well-Being (PGWB) Index. In: Wenger NK, Mattson ME, Furberg CF, Elinson J eds. Assessment of quality of life in clinical trials of cardiovascular therapies. Washington, DC, USA: Le Jacq Publishing Inc., 1984:170–83.
- Stjernman H, Grännö C, Järnerot G, et al. . Short Health Scale: a valid, reliable, and responsive instrument for subjective health assessment in Crohn's disease. Inflamm Bowel Dis 2008;14:47–52.
Source: PubMed