Dataset Information

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

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.

SUBMITTER: Fellermann K

PROVIDER: S-EPMC7724525 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Fellermann Klaus K Schiefke Ingolf I Rácz István I Derova Jelena J Jonaitis Laimas L Wehrum Sarah S Nacak Tanju T Greinwald Roland R

United European gastroenterology journal 20201007 10

<h4>Background</h4>In patients with mesalazine-refractory ulcerative colitis, systemic corticosteroids are the treatment of choice.<h4>Objective</h4>To evaluate the efficacy and safety of prolonged release budesonide granules for the induction of remission in patients with mesalazine-refractory ulcerative colitis.<h4>Methods</h4>Patients with mesalazine-refractory ulcerative colitis discontinued mesalazine at baseline and received 9 mg prolonged release budesonide granules daily for 8 weeks in t ...[more]

PMID: 33028169

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Project description:BackgroundUlcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation of the colon. Tanshinone IIA, a compound derived from traditional Chinese medicine, has demonstrated anti-inflammatory properties and may enhance treatment outcomes when combined with mesalazine. This study aims to determine the overall response rate of Tanshinone IIA in combination with mesalazine for the treatment of UC.MethodsWe reviewed articles from the establishment of the databases until April 2023 in the PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM databases. They included a randomized controlled trial in which the intervention group was given tanshinone IIA plus mesalazine (T + M), while the comparative group was given only mesalazine (M). We removed duplicates or similar papers; papers with no available full text or incomplete data; animal research; and review and systematic review articles. STATA 15.1 was used to analyze the data.ResultsThe perceived total effectiveness rate of T + M was found to be higher than M and the difference was found to be significant (P = 0.000). Additionally, pooled results show that TNF-α (P = 0.000) and CRP (P = 0.000) levels in the T + M group were all significantly lower than that in the M group. Furthermore, MHC-II expression in the T + M group was minors compared to that of the M group (P = 0.001). However, there was no significant difference in the incidence of adverse events between the T + M and M groups (P = 0.700).ConclusionThis meta-analysis demonstrates that combining tanshinone IIA with mesalazine significantly enhances the overall treatment efficacy for ulcerative colitis compared to mesalazine alone. Tanshinone IIA also exhibits anti-inflammatory effects by reducing TNF-α, CRP levels, and MHC-II expression without notably increasing adverse events. Despite some limitations, these findings suggest that tanshinone IIA can be a promising adjunctive therapy for ulcerative colitis. Further large-scale, multi-center studies are needed to confirm these results and establish the long-term safety and effectiveness of this combination therapy.

Project description:ObjectivesPhosphatidylcholine is a key component of the mucosal barrier. Treatment with modified release phosphatidylcholine aims to improve the impaired barrier function. The primary objective is to evaluate the efficacy of LT-02, a newly designed modified release phosphatidylcholine formula, in a multicenter setting.MethodsThis is a double-blinded, randomized, placebo-controlled, superiority study conducted in 24 ambulatory referral centers in Germany, Lithuania, and Romania. A total of 156 patients with an inadequate response to mesalazine, a disease activity score (Simple Clinical Colitis Activity Index (SCCAI)) of ≥ 5, and bloody diarrhea underwent treatment with 0, 0.8, 1.6, or 3.2 g LT-02. The primary end point was defined a priori as changes in SCCAI from baseline to the end of treatment. The primary statistical model was a general linear least-squares model. The study was funded by the sponsor Lipid Therapeutics, Heidelberg, Germany, and registered at http://clinicaltrials.gov/show/NCT01011322.ResultsBaseline characteristics and dropouts were well balanced between all groups. The primary analyses revealed an SCCAI drop of 33.3% in the placebo group (from 9.0 to 6.0 points) compared with 44.3% in the 0.8 g LT-02 (from 8.8 to 4.9, P>0.05) and 40.7% in the 1.6 g groups (from 8.6 to 5.1, P>0.05). The 3.2 g group improved 51.7% from 8.5 to 4.1 (P=0.030 in comparison with placebo). The remission rate was 15% (6/40) in the placebo group compared with 31.4% (11/35) in the highest LT-02 dose group (P=0.089). Mucosal healing was achieved in 32.5% of placebo patients compared with 47.4% of LT-02 patients (P=0.098); the rates for histologic remission were 20% compared with 40.5%, respectively (P=0.016). There were 17 (48.6%) treatment-emergent adverse events in the highest dose group (and 0 serious adverse events (SAEs)) compared with 22 (55%) in the placebo group (4 SAEs).ConclusionsThe primary end point analysis showed a statistically significant improvement in disease activity during LT-02 treatment in comparison with placebo. The drug was found to be very safe.

Dataset Information

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

Background

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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