背景:2017年,nusinersen的一种新疗法,通过重复鞘内注射递送的反义寡核苷酸,可用于脊髓性肌萎缩症(SMA)患者,而临床试验主要涉及儿童.自2020年以来,口头,选择性SMN2拼接改性剂risdiplam已经可用,但限制随着时间的推移而演变。在这种缺乏成年患者数据的特殊情况下,在确定该人群的治疗适应症和适当随访方面提出了许多问题.为了使法国获得治疗的机会均匀化,一个致力于成人SMA患者的国家多学科小组会议,命名SMA多学科团队会议,(SMDT)创建于2018年。我们的目的是分析SMDT在SMA成年患者决策过程中的价值,并提供有关治疗的指南。
方法:从2020年10月至2021年9月,收集从SMDT报告中提取的数据。主要结果是给出验证治疗计划建议的病例百分比。次要结果是要求的治疗类型,关于治疗的期望描述以及建议或随访和停药的描述。数据采用描述性统计分析。对于定量数据,使用Mann-Whitney检验或Studentt检验,对于定性数据,使用Fisher精确检验或χ2检验进行所需治疗类型之间的比较。
结果:在SMDT中讨论了107例患者的病例,平均年龄为35.3(16-62)。SMA2型为47,SMA3型为57。12例患者出现两次。在SMDT的122个演讲中,大多数与开始治疗相关的请求(nusinersen(n=46),risdiplam(n=54),治疗没有提及首选(n=5))或治疗切换(n=12)。Risdiplam要求显著关注老年患者(p=0.002),主要是2型SMA(p<0.0001),与nusinersen的要求相比,在运动和呼吸功能方面具有更大的疾病严重程度。在提交给SMDT的前一年,大多数患者经历了通过功能试验评估为MFM32或最严重患者的其他有意义的量表的运动无力恶化.讨论的患者中只有12%的病情稳定。只有49/122名患者(40.1%)表达了对治疗的明确期望。72例患者(67.2%)的SMDT批准了所要求的治疗。拒绝治疗的最常见原因是在讨论SMDT之前缺乏有关疾病过程的客观数据或不适当的患者期望。如果进行了足够的治疗前功能评估以评估自然史,则SMDT更有可能验证治疗请求(55%vs.32%),如果患者的运动功能恶化而不是稳定(p=0.029)。在获得批准治疗的患者中,对67/72例患者提出了定义进一步治疗无效(通常在治疗14个月后)的先验标准.
结论:在昂贵的治疗背景下,对SMA成人的对照研究很少,对他们的疗效评估可能很复杂,SMDT是“现实世界的观测站”,对建立有关治疗和随访适应症的国家建议非常感兴趣。
BACKGROUND: In 2017, a new treatment by nusinersen, an antisense oligonucleotide delivered by repeated intrathecal injections, became available for patients with spinal muscular atrophy (SMA), whereas clinical trials had mainly involved children. Since 2020, the oral, selective SMN2-splicing modifier risdiplam has been available with restrictions evolving with time. In this peculiar context of lack of data regarding adult patients, many questions were raised to define the indications of treatment and the appropriate follow-up in this population. To homogenize access to treatment in France, a national multidisciplinary team meeting dedicated to adult SMA patients, named SMA multidisciplinary team meeting, (SMDTs) was created in 2018. Our objective was to analyze the value of SMDTs in the decision-making process in SMA adult patients and to provide guidelines about treatment.
METHODS: From October 2020 to September 2021, data extracted from the SMDT reports were collected. The primary outcome was the percentage of cases in which recommendations on validating treatment plans were given. The secondary outcomes were type of treatment requested, description of expectations regarding treatment and description of recommendations or follow-up and discontinuation. Data were analyzed using descriptive statistics. Comparisons between the type of treatment requested were performed using Mann-Whitney test or the Student t test for quantitative data and the Fisher\'s exact test or the χ2 test for qualitative data.
RESULTS: Cases of 107 patients were discussed at the SMDTs with a mean age of 35.3 (16-62). Forty-seven were SMA type 2, and 57 SMA type 3. Twelve cases were presented twice. Out of 122 presentations to the SMDTs, most of requests related to the initiation of a treatment (nusinersen (n = 46), risdiplam (n = 54), treatment without mentioning preferred choice (n = 5)) or a switch of treatment (n = 12). Risdiplam requests concerned significantly older patients (p = 0.002), mostly SMA type 2 (p < 0.0001), with greater disease severity in terms of motor and respiratory function compared to requests for nusinersen. In the year prior to presentation to the SMDTs, most of the patients experienced worsening of motor weakness assessed by functional tests as MFM32 or other meaningful scales for the most severe patients. Only 12% of the patients discussed had a stable condition. Only 49/122 patients (40.1%) expressed clear expectations regarding treatment. The treatment requested was approved by the SMDTs in 72 patients (67.2%). The most common reasons to decline treatment were lack of objective data on the disease course prior discussion to the SMDTs or inappropriate patient\'s expectations. Treatment requests were more likely to be validated by the SMDTs if sufficient pre-therapeutic functional assessment had been performed to assess the natural history (55% vs. 32%) and if the patient had worsening rather than stable motor function (p = 0.029). In patients with approved treatment, a-priori criteria to define a further ineffectiveness of treatment (usually after 14 months of treatment) were proposed for 67/72 patients.
CONCLUSIONS: In the context of costly treatments with few controlled studies in adults with SMA, in whom assessment of efficacy can be complex, SMDTs are \'real-world observatories\' of great interest to establish national recommendations about indications of treatment and follow-up.