Safety and efficacy of multimatrix mesalamine in paediatric patients with mild-to-moderate ulcerative colitis: a phase 3, randomised, double-blind studyResearch in context
Summary: Background: Previous studies have demonstrated the tolerability and efficacy of multimatrix mesalamine in inducing and maintaining remission in adults with mild-to-moderate ulcerative colitis (UC). We evaluated the safety and efficacy of low-dose and high-dose once-daily multimatrix mesala...
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Elsevier
2023-11-01
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| Series: | EClinicalMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537023004091 |
| _version_ | 1827631711932907520 |
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| author | Nicholas Michael Croft Bartosz Korczowski Jarosław Kierkuś Beatriz Caballero Manoj Kumar Thakur |
| author_facet | Nicholas Michael Croft Bartosz Korczowski Jarosław Kierkuś Beatriz Caballero Manoj Kumar Thakur |
| author_sort | Nicholas Michael Croft |
| collection | DOAJ |
| description | Summary: Background: Previous studies have demonstrated the tolerability and efficacy of multimatrix mesalamine in inducing and maintaining remission in adults with mild-to-moderate ulcerative colitis (UC). We evaluated the safety and efficacy of low-dose and high-dose once-daily multimatrix mesalamine in children and adolescents with mild-to-moderate UC or those in remission. Methods: This prospective, randomised, parallel-group, phase 3 study (8-week double-blind acute [DBA] phase; 26-week double-blind maintenance [DBM] phase; and an additional 8-week, open-label acute [OLA] phase) was conducted in 33 sites across North America, Europe, and the Middle East between December 12, 2014, and November 28, 2018. Eligible patients aged 5–17 years and weighing 18–90 kg were randomised 1:1 to either low (900–2400 mg) or high (1800–4800 mg) oral doses of multimatrix mesalamine once daily, stratified by body weight. Interactive response technology was used for randomisation. The primary efficacy outcome was to estimate the clinical response of multimatrix mesalamine (two doses) in different weight groups. Efficacy and safety analyses were conducted in the safety analysis set (Clinicaltrials.gov: NCT02093663; Study completed). Findings: Overall, 107 patients were randomised into the DBA (n = 54) or DBM phase (n = 88; directly or after completing the double-blind or OLA phases); the overall safety analysis set included 105 patients. In the DBA phase, the high-dose group (n = 17; 65.4%) achieved a higher clinical response rate than the low-dose (n = 10; 37.0%) group; difference 28.3% (95% CI: 2.5–54.2; p = 0.039), odds ratio (OR) 3.21 (95% CI: 1.04–9.88). In the DBM phase at Week 26, similar proportions of patients maintained clinical response in the low-dose (n = 23; 54.8%) and high-dose (n = 24; 53.3%) groups: OR 0.99 (0.42–2.34); p = 0.981. Overall, 246 treatment-emergent adverse events (TEAEs) were reported in 73 patients (69.5%); 23 TEAEs in 14 patients (13.3%) were considered related to the study drug. No treatment-related deaths were reported. Interpretation: Our findings suggested that the benefit-risk ratio of once-daily multimatrix mesalamine in paediatric patients was favourable and comparable with that reported in adults with mild-to-moderate UC. Funding: Shire Development LLC, a Takeda company. |
| first_indexed | 2024-03-09T14:25:51Z |
| format | Article |
| id | doaj.art-7c91acd5669846f296f6e0f2d0cd3359 |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-03-09T14:25:51Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
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| series | EClinicalMedicine |
| spelling | doaj.art-7c91acd5669846f296f6e0f2d0cd33592023-11-28T07:26:39ZengElsevierEClinicalMedicine2589-53702023-11-0165102232Safety and efficacy of multimatrix mesalamine in paediatric patients with mild-to-moderate ulcerative colitis: a phase 3, randomised, double-blind studyResearch in contextNicholas Michael Croft0Bartosz Korczowski1Jarosław Kierkuś2Beatriz Caballero3Manoj Kumar Thakur4Faculty of Medicine, Blizard Institute, Queen Mary University of London, London, UK; Paediatric Gastroenterology, Royal London Children’s Hospital, Barts Health NHS Trust, London, UK; Corresponding author. Faculty of Medicine, Blizard Institute, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.Department of Pediatrics and Pediatric Gastroenterology, College of Medical Sciences, University of Rzeszów, Rzeszów, PolandDepartment of Gastroenterology, Hepatology and Feeding Disorders, Children’s Memorial Health Institute, Warsaw, PolandTakeda Clinical Science, Zurich, SwitzerlandTakeda Development Center Americas, Inc., Lexington, MA, USASummary: Background: Previous studies have demonstrated the tolerability and efficacy of multimatrix mesalamine in inducing and maintaining remission in adults with mild-to-moderate ulcerative colitis (UC). We evaluated the safety and efficacy of low-dose and high-dose once-daily multimatrix mesalamine in children and adolescents with mild-to-moderate UC or those in remission. Methods: This prospective, randomised, parallel-group, phase 3 study (8-week double-blind acute [DBA] phase; 26-week double-blind maintenance [DBM] phase; and an additional 8-week, open-label acute [OLA] phase) was conducted in 33 sites across North America, Europe, and the Middle East between December 12, 2014, and November 28, 2018. Eligible patients aged 5–17 years and weighing 18–90 kg were randomised 1:1 to either low (900–2400 mg) or high (1800–4800 mg) oral doses of multimatrix mesalamine once daily, stratified by body weight. Interactive response technology was used for randomisation. The primary efficacy outcome was to estimate the clinical response of multimatrix mesalamine (two doses) in different weight groups. Efficacy and safety analyses were conducted in the safety analysis set (Clinicaltrials.gov: NCT02093663; Study completed). Findings: Overall, 107 patients were randomised into the DBA (n = 54) or DBM phase (n = 88; directly or after completing the double-blind or OLA phases); the overall safety analysis set included 105 patients. In the DBA phase, the high-dose group (n = 17; 65.4%) achieved a higher clinical response rate than the low-dose (n = 10; 37.0%) group; difference 28.3% (95% CI: 2.5–54.2; p = 0.039), odds ratio (OR) 3.21 (95% CI: 1.04–9.88). In the DBM phase at Week 26, similar proportions of patients maintained clinical response in the low-dose (n = 23; 54.8%) and high-dose (n = 24; 53.3%) groups: OR 0.99 (0.42–2.34); p = 0.981. Overall, 246 treatment-emergent adverse events (TEAEs) were reported in 73 patients (69.5%); 23 TEAEs in 14 patients (13.3%) were considered related to the study drug. No treatment-related deaths were reported. Interpretation: Our findings suggested that the benefit-risk ratio of once-daily multimatrix mesalamine in paediatric patients was favourable and comparable with that reported in adults with mild-to-moderate UC. Funding: Shire Development LLC, a Takeda company.http://www.sciencedirect.com/science/article/pii/S2589537023004091EfficacyMild-to-moderate ulcerative colitisMultimatrix mesalaminePaediatricPhase 3 studySafety |
| spellingShingle | Nicholas Michael Croft Bartosz Korczowski Jarosław Kierkuś Beatriz Caballero Manoj Kumar Thakur Safety and efficacy of multimatrix mesalamine in paediatric patients with mild-to-moderate ulcerative colitis: a phase 3, randomised, double-blind studyResearch in context EClinicalMedicine Efficacy Mild-to-moderate ulcerative colitis Multimatrix mesalamine Paediatric Phase 3 study Safety |
| title | Safety and efficacy of multimatrix mesalamine in paediatric patients with mild-to-moderate ulcerative colitis: a phase 3, randomised, double-blind studyResearch in context |
| title_full | Safety and efficacy of multimatrix mesalamine in paediatric patients with mild-to-moderate ulcerative colitis: a phase 3, randomised, double-blind studyResearch in context |
| title_fullStr | Safety and efficacy of multimatrix mesalamine in paediatric patients with mild-to-moderate ulcerative colitis: a phase 3, randomised, double-blind studyResearch in context |
| title_full_unstemmed | Safety and efficacy of multimatrix mesalamine in paediatric patients with mild-to-moderate ulcerative colitis: a phase 3, randomised, double-blind studyResearch in context |
| title_short | Safety and efficacy of multimatrix mesalamine in paediatric patients with mild-to-moderate ulcerative colitis: a phase 3, randomised, double-blind studyResearch in context |
| title_sort | safety and efficacy of multimatrix mesalamine in paediatric patients with mild to moderate ulcerative colitis a phase 3 randomised double blind studyresearch in context |
| topic | Efficacy Mild-to-moderate ulcerative colitis Multimatrix mesalamine Paediatric Phase 3 study Safety |
| url | http://www.sciencedirect.com/science/article/pii/S2589537023004091 |
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