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

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.