Efficacy and safety of prolonged release budesonide granules in mesalazine-refractory ulcerative colitis: A multi-centre Phase IIa study (TOPICAL-1)

Klaus Fellermann (Coresponding Author), Ingolf Schiefke, István Rácz, Jeļena Derova, Laimas Jonaitis, Sarah Wehrum, Tanju Nacak, Roland Greinwald

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1 Citation (Scopus)

Abstract

Background: In patients with mesalazine-refractory ulcerative colitis, systemic corticosteroids are the treatment of choice. Objective: To evaluate the efficacy and safety of prolonged release budesonide granules for the induction of remission in patients with mesalazine-refractory ulcerative colitis. Methods: Patients with mesalazine-refractory ulcerative colitis discontinued mesalazine at baseline and received 9 mg prolonged release budesonide granules daily for 8 weeks in this open-label, phase IIa study, followed by a 2-week follow-up phase wherein patients continued treatment on alternate days (EudraCT number 2014-005635-14; ClinicalTrials.gov identifier NCT02550418). The primary endpoint was clinical remission (Clinical Activity Index ≤4; stool frequency <18 per week; absence of rectal bleeding) at Week 8. Secondary endpoints included clinical, endoscopic and histological measures of disease at Week 8. A post hoc analysis assessed histo-endoscopic mucosal healing. Treatment-emergent adverse events and morning cortisol levels were assessed throughout the treatment and follow-up phases. Results: A total of 61 patients were included in the intention-to-treat population; 50 were included in the follow-up analysis set. Clinical remission was achieved in 29 patients (47.5%; 95% confidence interval: 34.6–60.7%) by Week 8. Mean stool and bloody stool frequency decreased significantly from 32.5 to 22.9 per week (p<0.0001) and from 17.6 to 8.1 per week (p<0.0001), respectively. Rates of mucosal healing, endoscopic remission and histological remission were 58.0%, 54.0% and 36.0%, respectively. Histo-endoscopic mucosal healing was achieved by 34.0% of patients. Twenty-four patients (39.3%) experienced treatment-emergent adverse events, of which gastrointestinal disorders (16.4%) were the most common. Mean morning cortisol levels were not significantly suppressed by Week 8. Conclusions: Treatment with prolonged release budesonide granules for 8 weeks was associated with clinical, endoscopic and histological remission and demonstrated a favourable safety profile in patients with mesalazine-refractory ulcerative colitis. These results warrant further investigation into the potential of prolonged release budesonide granules as an alternative treatment for this patient population.

Original languageEnglish
Pages (from-to)1186-1195
JournalUnited European Gastroenterology Journal
Volume8
Issue number10
DOIs
Publication statusPublished - Dec 2020
Externally publishedYes

Keywords

  • efficacy
  • Prolonged release budesonide granules
  • safety
  • TOPICAL-1
  • ulcerative colitis

Field of Science

  • 3.2 Clinical medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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