Abstract：
OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease. Riluzole may increase survival and delay the need for mechanical ventilation. The CAESAR project (\'Comparative evaluation of the efficacy and safety of drugs used in rare neuromuscular and neurodegenerative diseases\', FV AIFA project 2012-2013-2014) involves evaluating prescribing patterns, and analysing effectiveness and comparative safety of drugs, in patients with neurodegenerative diseases. The aim of this study is to evaluate adherence to riluzole in patients with ALS during the first year of use, identifying adherence clusters.
METHODS: A retrospective cohort study was conducted using administrative data from Latium, Tuscany, and Umbria. We identified subjects with a new diagnosis of ALS between 2014 and 2019, with the first dispensation of riluzole within 180 days of diagnosis. We considered a two-year look-back period for the characterization of patients, and we followed them from the date of first dispensing of riluzole for 1 year. We calculated 12 monthly adherence measures, through a modified version of the Medication Possession Ratio, estimating drug coverage with Defined Daily Dose. Adherence trajectories were identified using a three-step method: (1) calculation of statistical measures; (2) principal component analysis; (3) cluster analysis. Patient characteristics at baseline and during follow-up were described and compared between adherence groups identified.
RESULTS: We included 264 ALS patients as new users of riluzole in Latium, 344 in Tuscany, and 63 in Umbria. We observed a higher frequency of males (56.2%) and a mean age of 67.4 (standard deviation, SD, 10.4) in the overall population. We identified two clusters in all regions: one more numerous, including adherent patients (60%, 74%, 88%, respectively), and another one including patients who discontinued therapy (40%, 26%, 12%, respectively). In Tuscany patients discontinuing riluzole more frequently died (28.6% vs. 15.4%, p-value <0.01). Additionally, low-adherers had a higher frequency of central nervous system disorders (69.0% vs. 52.5%, p-value 0.01), and a greater use of non-pharmacological treatments (p-values ≤0.01 for invasive ventilation and tracheostomy). We did not observe any differences in Lazio, whereas in Umbria we observed a higher use of drugs for dementia-related psychiatric problems among low-adherers (57.1% vs. 7.8%, respectively, p-value <0.01), although with small numbers.
CONCLUSIONS: Most ALS patients who start riluzole adhere to therapy during the first year. Patients who discontinue therapy early show greater fragility and mortality.
METHODS: A retrospective cohort study was conducted using administrative data from Latium, Tuscany, and Umbria. We identified subjects with a new diagnosis of ALS between 2014 and 2019, with the first dispensation of riluzole within 180 days of diagnosis. We considered a two-year look-back period for the characterization of patients, and we followed them from the date of first dispensing of riluzole for 1 year. We calculated 12 monthly adherence measures, through a modified version of the Medication Possession Ratio, estimating drug coverage with Defined Daily Dose. Adherence trajectories were identified using a three-step method: (1) calculation of statistical measures; (2) principal component analysis; (3) cluster analysis. Patient characteristics at baseline and during follow-up were described and compared between adherence groups identified.
RESULTS: We included 264 ALS patients as new users of riluzole in Latium, 344 in Tuscany, and 63 in Umbria. We observed a higher frequency of males (56.2%) and a mean age of 67.4 (standard deviation, SD, 10.4) in the overall population. We identified two clusters in all regions: one more numerous, including adherent patients (60%, 74%, 88%, respectively), and another one including patients who discontinued therapy (40%, 26%, 12%, respectively). In Tuscany patients discontinuing riluzole more frequently died (28.6% vs. 15.4%, p-value <0.01). Additionally, low-adherers had a higher frequency of central nervous system disorders (69.0% vs. 52.5%, p-value 0.01), and a greater use of non-pharmacological treatments (p-values ≤0.01 for invasive ventilation and tracheostomy). We did not observe any differences in Lazio, whereas in Umbria we observed a higher use of drugs for dementia-related psychiatric problems among low-adherers (57.1% vs. 7.8%, respectively, p-value <0.01), although with small numbers.
CONCLUSIONS: Most ALS patients who start riluzole adhere to therapy during the first year. Patients who discontinue therapy early show greater fragility and mortality.
摘要：
目标：肌萎缩侧索硬化症（ALS）是一种罕见的神经退行性疾病。利鲁唑可以增加生存率并延迟机械通气的需要。CAESAR项目（“用于罕见神经肌肉和神经退行性疾病的药物的疗效和安全性的比较评估”，FVAIFA项目2012-2013-2014)涉及评估处方模式，并分析药物的有效性和相对安全性，神经退行性疾病患者。这项研究的目的是评估ALS患者在使用第一年对利鲁唑的依从性，识别依从性集群。
方法：使用Latium的管理数据进行了一项回顾性队列研究，托斯卡纳,和翁布里亚.我们在2014年至2019年之间确定了新诊断为ALS的受试者，在诊断后180天内首次分配了利鲁唑。我们考虑了两年的回顾期，用于患者的表征，我们从第一次分配利鲁唑的日期开始跟踪他们1年。我们计算了12个月的坚持措施，通过修改版本的药物持有率，用确定的每日剂量估计药物覆盖率。使用三步方法识别粘附轨迹：（1）统计度量的计算；（2）主成分分析；（3）聚类分析。描述基线和随访期间的患者特征，并在确定的依从组之间进行比较。
结果：我们纳入了264名ALS患者作为Latium利鲁唑的新使用者，344在托斯卡纳，和63在翁布里亚。我们观察到男性的频率更高（56.2%），平均年龄为67.4岁（标准差，SD,10.4）在总人口中。我们在所有地区都确定了两个集群：还有一个，包括粘附患者(60%，74%,88%,分别)，另一个包括停止治疗的患者(40%，26%,12%,分别)。在托斯卡纳，停止利鲁唑的患者更频繁地死亡（28.6％vs.15.4%,p值<0.01)。此外,低用户的中枢神经系统疾病发生率较高(69.0%vs.52.5%,p值0.01)，以及更多地使用非药物治疗（有创通气和气管造口术的p值≤0.01）。我们没有观察到拉齐奥的任何差异，而在翁布里亚，我们观察到在低信奉者中，治疗痴呆相关精神问题的药物使用率较高(57.1%vs.7.8%,分别,p值<0.01)，虽然数字很小。
结论：大多数开始使用利鲁唑的ALS患者在第一年坚持治疗。早期停止治疗的患者表现出更大的脆弱性和死亡率。
方法：使用Latium的管理数据进行了一项回顾性队列研究，托斯卡纳,和翁布里亚.我们在2014年至2019年之间确定了新诊断为ALS的受试者，在诊断后180天内首次分配了利鲁唑。我们考虑了两年的回顾期，用于患者的表征，我们从第一次分配利鲁唑的日期开始跟踪他们1年。我们计算了12个月的坚持措施，通过修改版本的药物持有率，用确定的每日剂量估计药物覆盖率。使用三步方法识别粘附轨迹：（1）统计度量的计算；（2）主成分分析；（3）聚类分析。描述基线和随访期间的患者特征，并在确定的依从组之间进行比较。
结果：我们纳入了264名ALS患者作为Latium利鲁唑的新使用者，344在托斯卡纳，和63在翁布里亚。我们观察到男性的频率更高（56.2%），平均年龄为67.4岁（标准差，SD,10.4）在总人口中。我们在所有地区都确定了两个集群：还有一个，包括粘附患者(60%，74%,88%,分别)，另一个包括停止治疗的患者(40%，26%,12%,分别)。在托斯卡纳，停止利鲁唑的患者更频繁地死亡（28.6％vs.15.4%,p值<0.01)。此外,低用户的中枢神经系统疾病发生率较高(69.0%vs.52.5%,p值0.01)，以及更多地使用非药物治疗（有创通气和气管造口术的p值≤0.01）。我们没有观察到拉齐奥的任何差异，而在翁布里亚，我们观察到在低信奉者中，治疗痴呆相关精神问题的药物使用率较高(57.1%vs.7.8%,分别,p值<0.01)，虽然数字很小。
结论：大多数开始使用利鲁唑的ALS患者在第一年坚持治疗。早期停止治疗的患者表现出更大的脆弱性和死亡率。
