Kleijnen Systematic Reviews Ltd, York, YO19 6FD, UK.
Orchard Therapeutics, 245 Hammersmith Road, 3rd Floor, London, W6 8PW, UK.
Orphanet J Rare Dis. 2023 Aug 29;18(1):248. doi: 10.1186/s13023-023-02814-2.
To understand the benefit-risk profile for historical and current treatments for MLD.
A systematic review was conducted on the effectiveness, safety, and costs of MLD treatments: allogeneic haematopoietic stem cell transplantation (HSCT) and atidarsagene autotemcel (arsa-cel) according to best practice.
A total of 6940 titles and abstracts were retrieved from the literature searches and 26 from other sources. From these, 35 manuscripts reporting on a total of 12 studies were selected for inclusion in the review. There were no controlled multi-armed trials. However, we provide observations comparing two interventional therapies (alloHSCT and arsa-cel) and each of these to standard/supportive care (natural history). There were no benefits for survival, gross motor function and cognitive function for LI patients receiving alloHSCT, as patients experienced disease progression similar to LI natural history. For juvenile patients receiving alloHSCT, no differences in survival were observed versus natural history, however stabilisation of cognitive and motor function were reported for some patients (particularly for pre- or minimally-symptomatic LJ patients), while others experienced disease progression. Furthermore, alloHSCT was associated with severe complications such as treatment-related mortality, graft versus host disease, and re-transplantation in both LI and EJ treated patients. Most LI and EJ patients treated with arsa-cel appeared to have normal development, preservation, or slower progression of gross motor function and cognitive function, in contrast to the rapid decline observed in natural history patients. A survival benefit for arsa-cel versus natural history and versus alloHSCT was observed in LI patients.LI and EJ patients treated with arsa-cel had better gross motor function and cognitive function compared to alloHSCT, which had limited effect on motor and cognitive decline. No data has been reported for arsa-cel treatment of LJ patients.
Overall, this systematic review indicates that compared to NHx and HSCT, treatment with arsa-cel results in clinically relevant benefits in LI and EJ MLD patients by preserving cognitive function and motor development in most patients, and increased survival for LI patients. Nevertheless, further research is required to confirm these findings, given they are based on results from non-RCT studies.
了解 ML 疾病历史和当前治疗的获益-风险概况。
根据最佳实践，对 ML 疾病治疗的有效性、安全性和成本进行了系统评价：异体造血干细胞移植（HSCT）和 atidarsagene autotemcel（arsa-cel）。
从文献检索中检索到 6940 个标题和摘要，从其他来源检索到 26 个。从这些中，选择了 35 篇报告总共 12 项研究的手稿纳入综述。没有对照多臂试验。然而，我们提供了将两种介入治疗（alloHSCT 和 arsa-cel）进行比较的观察结果，以及将每种治疗与标准/支持性治疗（自然史）进行比较的观察结果。接受 alloHSCT 的 LI 患者在生存、总体运动功能和认知功能方面没有获益，因为患者的疾病进展与 LI 自然史相似。对于接受 alloHSCT 的青少年患者，与自然史相比，生存没有差异，然而一些患者报告了认知和运动功能的稳定（特别是对于预症状或轻度症状的 LJ 患者），而其他患者则经历了疾病进展。此外，alloHSCT 与严重并发症相关，如治疗相关死亡率、移植物抗宿主病和 LI 和 EJ 治疗患者的再移植。接受 arsa-cel 治疗的大多数 LI 和 EJ 患者似乎具有正常的发育、保留或总体运动功能和认知功能的进展缓慢，与自然史患者观察到的快速下降形成对比。LI 患者接受 arsa-cel 治疗的生存获益优于自然史和 alloHSCT。LI 和 EJ 患者接受 arsa-cel 治疗的总体运动功能和认知功能优于 alloHSCT，alloHSCT 对运动和认知下降的影响有限。尚未报告 arsa-cel 治疗 LJ 患者的数据。
总体而言，这项系统评价表明，与 NHx 和 HSCT 相比，arsa-cel 治疗在 LI 和 EJ ML 疾病患者中具有临床相关的益处，通过在大多数患者中保留认知功能和运动发育，并且增加 LI 患者的生存。然而，鉴于这些发现基于非 RCT 研究的结果，需要进一步的研究来证实这些发现。
