Dataset Information

Budesonide Multimatrix Is Efficacious for Mesalamine-refractory, Mild to Moderate Ulcerative Colitis: A Randomised, Placebo-controlled Trial.

ABSTRACT:

Background and aims

Safety and efficacy of budesonide multimatrix, an oral extended-release second-generation corticosteroid designed for targeted delivery throughout the colon, were examined for induction of remission in patients with mild to moderate ulcerative colitis refractory to baseline mesalamine therapy.

Methods

A randomised, double-blind, placebo-controlled, multicentre trial evaluated efficacy and safety of budesonide multimatrix for induction of remission [ulcerative colitis disease activity index score ≥ 4 and ≤ 10] in 510 adults randomised to once-daily oral budesonide multimatrix 9 mg or placebo for 8 weeks. Patients continued baseline treatment with oral mesalamine ≥ 2.4 g/day.

Results

Combined clinical and endoscopic remission at Week 8 was achieved by 13.0% and 7.5% of patients receiving budesonide multimatrix [n = 230] or placebo [n = 228], respectively, in the modified intention-to-treat population [p = 0.049]. Clinical remission [ulcerative colitis disease activity index rectal bleeding and stool frequency subscale scores of 0] was similar in both groups [p = 0.70]. More patients receiving budesonide multimatrix vs placebo achieved endoscopic remission [ulcerative colitis disease activity index mucosal appearance subscale score of 0; 20.0% vs 12.3%; p = 0.02] and histological healing [27.0% vs 17.5%; p = 0.02]. Adverse event rates were similar [budesonide multimatrix, 31.8%; placebo, 27.1%]. Mean morning cortisol concentrations decreased at Weeks 2, 4, and 8 with budesonide multimatrix but remained within the normal range.

Conclusion

Budesonide multimatrix was safe and efficacious for inducing clinical and endoscopic remission for mild to moderate ulcerative colitis refractory to oral mesalamine therapy.

SUBMITTER: Rubin DT

PROVIDER: S-EPMC5881669 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundUlcerative colitis (UC) is associated with lower health-related quality of life (HRQoL), and with disease activity predicting lower HRQoL and worse work-related outcomes. The current study examined the burden of UC on patients' HRQoL, as well as changes in patients' HRQoL and work-related outcomes following short-term and long-term treatment with multimatrix mesalamine, and their correspondence with changes in disease activity.MethodsData were from an open-label, multinational, prospective trial (ClinicalTrials.gov identifier: NCT01124149) of 717 adults with active mild-to-moderate UC who were treated with 4.8 g/day multimatrix mesalamine tablets once daily for eight weeks (acute phase). Four-hundred sixty-one patients who achieved partial or complete clinical and endoscopic remission subsequently received treatment with daily 2.4 g/day multimatrix mesalamine for 12 months (maintenance phase). At baseline, Week 8, and Month 12, patients were administered patient-reported outcomes (PRO) measures of HRQoL (the SF-12v2® Health Survey [SF-12v2] and Short Inflammatory Bowel Disease Questionnaire) and work-related outcomes (Work Productivity and Activity Impairment questionnaire, UC-specific version). SF-12v2 scores were compared to the U.S. general population using Analysis of Variance models to assess burden of UC on HRQoL. Mixed-effects repeated-measures models compared PRO scores across visits to assess change in PRO scores over time. Correlations examined the correspondence of changes in PRO scores with changes on a modified UC disease activity index (UC-DAI).ResultsBaseline burden of disease observed on all SF-12v2 domains was partially eliminated at Week 8 and completely eliminated at Month 12. Statistically significant improvements from baseline were observed at both Week 8 and Month 12 for all PRO scores (all P < 0.001). Decreases in UC-DAI scores significantly predicted improvements in PRO scores during the acute treatment phase.ConclusionsPatients with UC receiving daily multimatrix mesalamine treatment showed significant improvements in all measured domains of HRQoL and work-related outcomes. Patients who achieved partial or complete clinical and endoscopic remission maintained these improvements for most of these domains over 12 months with continued daily treatment. Changes in HRQoL and work-related outcomes were inversely related to changes in disease activity. Findings support the effectiveness of multimatrix mesalamine for improving, and sustaining improvements, in HRQoL and work-related outcomes.

Project description:Background:Disease activity of patients with ulcerative colitis (UC) predicts health-related quality of life (HRQL) and work-related outcomes (eg, absenteeism, productivity). We tested whether outcomes differed among patients in complete (clinical and endoscopic) remission, partial remission, or not in remission following treatment with multimatrix mesalamine. Methods:Data were from an open-label, multicountry, prospective trial (ClinicalTrials.gov identifier: NCT01124149) of 717 adults with active mild-to-moderate UC treated with 4.8 g/day multimatrix mesalamine tablets for 8 weeks (induction period); 459 patients who achieved partial or complete remission received daily 2.4 g/day multimatrix mesalamine for 12 additional months (maintenance period). HRQL (SF-12v2 Health Survey and Short Inflammatory Bowel Disease Questionnaire) and work-related outcomes (Work Productivity and Activity Impairment questionnaire) were assessed at baseline and final visits of each treatment period. Differences in scores by remission status within each treatment period were tested using analysis of variance and analysis of covariance models, whereas mixed-effects models with repeated measures tested changes over time. Results:At their final visit of each treatment period, patients in partial remission scored significantly better on all HRQL and work-related domains than patients not in remission (all Bonferroni-adjusted P < 0.05). Scores for patients in partial remission were, almost without exception, statistically equivalent to those for patients in complete remission. Fluctuating between complete and partial remission during maintenance treatment had no impact on outcomes. Conclusions:Patients in partial remission following multimatrix mesalamine treatment had HRQL and work-related outcomes equivalent to patients in complete remission. Achievement and maintenance of partial remission may be sufficient for improvements in patients' functioning, well-being, and work performance.