Cetin Hakan, Klickovic Uros, Rath Jakob, Zulehner Gudrun, Füzi Judith, Reichardt Berthold, Hagmann Michael, Wanschitz Julia, Löscher Wolfgang N, Auff Eduard, Zimprich Fritz
Department of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria,
J Neurol. 2015 Jul;262(7):1698-705. doi: 10.1007/s00415-015-7767-7. Epub 2015 May 10.
The aim of this study was to evaluate associations between co-medications and survival of patients with amyotrophic lateral sclerosis (ALS). Prescription databases of the Austrian sickness funds covering more than 5 million people formed the basis of this study. ALS cases were deduced from riluzole prescriptions during the study period from January 1, 2008, to June 30, 2012. After adjusting for potential confounding factors associations between co-medications and ALS survival were analyzed. A total of 522 ALS patients could be identified during the study period. Sixteen of the most frequently used drug classes were considered for the survival analyses of which two were nominally associated with ALS survival. Proton pump inhibitors (PPI) were negatively correlated with survival (HR 1.34, 95 % CI 1.04-1.73) and centrally acting muscle relaxants (CAMR) showed a positive association (HR 0.56, 95 % CI 0.39-0.81). After correcting for multiple testing, the association between CAMR and ALS survival remained significant (p = 0.03). In conclusion, this is the first study systematically evaluating potential associations between commonly used drugs and ALS disease course. We report a positive association between CAMR use and survival, which may have derived from an indication bias representing the better prognosis of the upper motor neuron predominant disease variant. However, this is still interesting since it demonstrates the sensitivity of our study design to pick up survival effects. The use of large prescription registries could thus provide a valuable basis to find clues to underlying pathophysiological mechanisms in ALS.
本研究旨在评估合并用药与肌萎缩侧索硬化症（ALS）患者生存率之间的关联。奥地利疾病基金涵盖超过500万人的处方数据库构成了本研究的基础。在2008年1月1日至2012年6月30日的研究期间，从利鲁唑处方中推断出ALS病例。在调整潜在混杂因素后，分析合并用药与ALS生存率之间的关联。在研究期间共识别出522例ALS患者。在生存分析中考虑了16种最常用的药物类别，其中两种与ALS生存率存在名义上的关联。质子泵抑制剂（PPI）与生存率呈负相关（HR 1.34，95%CI 1.04-1.73），中枢性肌肉松弛剂（CAMR）显示出正相关（HR 0.56，95%CI 0.39-0.81）。在进行多重检验校正后，CAMR与ALS生存率之间的关联仍然显著（p = 0.03）。总之，这是第一项系统评估常用药物与ALS病程之间潜在关联的研究。我们报告了CAMR使用与生存率之间的正相关，这可能源于一种指示性偏倚，代表了上运动神经元为主的疾病变体的较好预后。然而，这仍然很有趣，因为它证明了我们研究设计对发现生存效应的敏感性。因此，使用大型处方登记库可为寻找ALS潜在病理生理机制的线索提供有价值的基础。
