Health and Social Research Center, Universidad de Castilla-La Mancha, Cuenca, Spain.
Facultad de Enfermería de Albacete, Universidad de Castilla-La Mancha, Albacete, Spain.
Paediatr Drugs. 2024 Nov;26(6):695-707. doi: 10.1007/s40272-024-00655-5. Epub 2024 Sep 27.
Vamorolone has recently been approved for the management of Duchenne muscular dystrophy to replace glucocorticosteroids, which theoretically have more side effects. However, its efficacy and safety profile is unclear.
We aimed to assess the efficacy of vamorolone in Duchenne muscular dystrophy through the 6-minute walk test (6MWT), the North Star Ambulatory Assessment (NSAA), time to stand velocity (TTSTAND), time to run 10 m (TTRW), time to climb four stairs (TTCLIMB) and a safety profile.
A systematic search was conducted in MEDLINE, Scopus, Web of Science and the Cochrane Library from inception to June 2024 (PROSPERO: CRD42024558413) for studies evaluating the effect or safety profile of vamorolone in a population with Duchenne muscular dystrophy on 6MWT, NSAA and TTSTAND. TTRW, TTCLIMB and a safety profile were included. The risk of bias was assessed using the Cochrane Collaboration's risk of bias tool (RoB2) and the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group from the US National Institutes of Health National Heart, Lung, and Blood Institute, depending on the type of design. Results were expressed as mean differences or proportions with 95% confidence intervals (CIs), depending on the outcome.
Six studies with a total of 145 individuals with Duchenne muscular dystrophy and a baseline age between 4.7 and 5.5 years were included in the systematic review. Overall, the most effective dose was 6 mg/kg/day. At 24 weeks, this dose showed a statistically significant effect compared with the untreated cohorts of 41.60 m (95% CI 14.30, 68.90) on the 6MWT, 3.57 points (95% CI 1.89, 5.25) on the NSAA, 0.06 events/s (95% CI 0.02, 0.10) on the TTSTAND, approximately 0.25 m/s on the TTRW and 0.04 (95% CI -0.00, 0.08) to 0.07 events/s (95% CI 0.03, 0.11) on the TTCLIMB. There was some discrepancy in the statistical significance of some studies, although the direction of the effect was usually similar. In general, the effect was maintained in the extension studies. Adverse events were less frequent than in historical cohorts treated with glucocorticoids. Finally, the risk of bias in the included studies was low.
According to our results, vamorolone offers a statistically and clinically significant benefit in the management of Duchenne muscular dystrophy, with fewer side effects than glucocorticoids. However, the number of studies limits the interpretability and generalisability of these data, requiring more studies with more participants to perform a meta-analysis.
Vamorolone 最近被批准用于治疗杜氏肌营养不良症，以替代糖皮质激素，理论上糖皮质激素的副作用更多。然而，其疗效和安全性尚不清楚。
我们旨在通过 6 分钟步行测试（6MWT）、北美星动态评估（NSAA）、站立速度时间（TTSTAND）、10 米跑步时间（TTRW）、爬四级楼梯时间（TTCLIMB）和安全性评估来评估 vamorolone 在杜氏肌营养不良症中的疗效。
从成立到 2024 年 6 月，我们在 MEDLINE、Scopus、Web of Science 和 Cochrane 图书馆中进行了系统检索，以评估在杜氏肌营养不良症人群中使用 vamorolone 的效果或安全性（PROSPERO：CRD42024558413），评估 6MWT、NSAA 和 TTSTAND。包括 TTRW、TTCLIMB 和安全性。使用 Cochrane 协作组的偏倚风险工具（RoB2）和美国国立卫生研究院国家心脏、肺和血液研究所的无对照组前后（Pre-Post）研究质量评估工具（Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group from the US National Institutes of Health National Heart, Lung, and Blood Institute）评估偏倚风险，具体取决于设计类型。结果以均数差或 95%置信区间（CI）表示，具体取决于结局。
共纳入 6 项研究，总计 145 例杜氏肌营养不良症患者，基线年龄在 4.7 至 5.5 岁之间。总体而言，最有效的剂量为 6mg/kg/天。在 24 周时，与未治疗组相比，该剂量在 6MWT 上的效果具有统计学意义，为 41.60m（95%CI 14.30，68.90），在 NSAA 上为 3.57 分（95%CI 1.89，5.25），在 TTSTAND 上为 0.06 次/s（95%CI 0.02，0.10），在 TTRW 上约为 0.25m/s，在 TTCLIMB 上为 0.04（95%CI-0.00，0.08）至 0.07 次/s（95%CI 0.03，0.11）。尽管效果的方向通常相似，但一些研究的统计学意义存在差异。一般来说，在扩展研究中，效果得到了维持。与接受糖皮质激素治疗的历史队列相比，不良事件的发生频率较低。最后，纳入研究的偏倚风险较低。
根据我们的结果，vamorolone 在治疗杜氏肌营养不良症方面具有统计学和临床意义上的益处，且副作用少于糖皮质激素。然而，研究数量限制了这些数据的可解释性和普遍性，需要更多的参与者进行 meta 分析。
