Croft Nicholas Michael, Korczowski Bartosz, Kierkuś Jarosław, Caballero Beatriz, Thakur Manoj Kumar
Faculty of Medicine, Blizard Institute, Queen Mary University of London, London, UK.
Paediatric Gastroenterology, Royal London Children's Hospital, Barts Health NHS Trust, London, UK.
EClinicalMedicine. 2023 Oct 6;65:102232. doi: 10.1016/j.eclinm.2023.102232. eCollection 2023 Nov.
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.
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).
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.
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.
Shire Development LLC, a Takeda company.
既往研究已证实多基质美沙拉嗪在诱导和维持轻至中度溃疡性结肠炎（UC）成年患者缓解方面的耐受性和疗效。我们评估了低剂量和高剂量每日一次多基质美沙拉嗪在轻至中度UC儿童和青少年患者或处于缓解期患者中的安全性和疗效。
这项前瞻性、随机、平行组、3期研究（8周双盲急性期[DBA]；26周双盲维持期[DBM]；以及额外8周的开放标签急性期[OLA]）于2014年12月12日至2018年11月28日在北美、欧洲和中东的33个地点进行。符合条件的年龄在5至17岁、体重18至90千克的患者按体重分层，以1:1的比例随机分为每日口服低剂量（900 - 2400毫克）或高剂量（1800 - 4800毫克）的多基质美沙拉嗪。采用交互式应答技术进行随机分组。主要疗效指标是评估不同体重组中多基质美沙拉嗪（两种剂量）的临床反应。在安全性分析集（Clinicaltrials.gov：NCT02093663；研究已完成）中进行疗效和安全性分析。
总体而言，107例患者被随机分配至DBA期（n = 54）或DBM期（n = 88；直接进入或在完成双盲或OLA期后进入）；总体安全性分析集包括105例患者。在DBA期，高剂量组（n = 17；65.4%）的临床反应率高于低剂量组（n = 10；37.0%）；差异为28.3%（95%CI：2.5 - 54.2；p = 0.039），比值比（OR）为3.21（95%CI：1.04 - 9.88）。在第26周的DBM期，低剂量组（n = 23；54.8%）和高剂量组（n = 24；53.3%）中维持临床反应的患者比例相似：OR为0.99（0.42 - 2.34）；p = 0.981。总体而言，73例患者（69.5%）报告了246例治疗中出现的不良事件（TEAE）；14例患者（13.3%）出现的23例TEAE被认为与研究药物有关。未报告与治疗相关的死亡病例。
我们的研究结果表明，每日一次多基质美沙拉嗪在儿科患者中的获益风险比是有利的，且与轻至中度UC成年患者中报告的情况相当。
武田公司旗下的夏尔开发有限责任公司。
