Izquierdo Guillermo, Damas Fátima, Páramo Maria Dolores, Ruiz-Peña Juan Luis, Navarro Guillermo
Servicio de Neurología, Hospital Universitario Virgen Macarena, Sevilla, Andalucia, Spain.
PLoS One. 2017 Apr 28;12(4):e0176174. doi: 10.1371/journal.pone.0176174. eCollection 2017.
Fingolimod approval was based mainly on two clinical trials, FREEDOMS and TRANSFORMS, which demonstrated the efficacy and safety of fingolimod in patients with multiple sclerosis (MS). We present an observational study that validates these trials findings in a real-world setting, whereby the effectiveness and safety of fingolimod was assessed in Seville's' (Spain) clinical practice. This retrospective study in MS patients assessed effectiveness (relapses, EDSS, gadolinium-enhancing T1 and new/enlarged T2-weighted lesions): total cohort (n = 249) and stratified according to prior treatment (glatiramer acetate/interferon beta-1 [immunomodulator], natalizumab, naïve), gender, basal EDSS score, basal Gd+ lesions, ARR prior to treatment, age at treatment initiation and number of prior treatments. A multivariante model was used to assess the ARR with baseline characteristics. The safety profile (adverse events [AEs]) was also described. Fingolimod reduced the annualized relapse rate (ARR) by 75%, 67% and 85% in the total cohort, patients previously treated with immunomodulatory and naïve patients (p<0.0001 all cases). However, patients previously treated with natalizumab kept a constant ARR. The ARR results and the consequent increase in the proportion of relapse-free patients were independent of the age at treatment initiation, number of prior treatments, gender and basal Gd+ lesions. Although fingolimod was effective regardless the basal EDSS score and ARR prior to fingolimod treatment, better outcomes were observed in patients with basal EDSS score <3 (0.2 vs. 0.4; p = 0.0244) and ARR ≥ 2 prior to fingolimod treatment (p = 0.0338). Only the basal EDSS score was association with ARR in the first 24 months of fingolimod treatment in the multivariante model (p = 0.0439). The cumulative probability of disability progression was 20% (month-24) in the total cohort, and was independent from prior treatment, age at treatment initiation, number of prior treatments, gender, basal EDSS score, basal Gd+ lesions and ARR prior to treatment. The real-world fingolimod benefits observed in this study seem to be similar than those observed in previous clinical trials.
芬戈莫德的获批主要基于两项临床试验，即FREEDOMS和TRANSFORMS，这两项试验证明了芬戈莫德在多发性硬化症（MS）患者中的疗效和安全性。我们开展了一项观察性研究，在现实环境中验证这些试验结果，即在西班牙塞维利亚的临床实践中评估芬戈莫德的有效性和安全性。这项针对MS患者的回顾性研究评估了有效性（复发、扩展残疾状态量表[EDSS]、钆增强T1加权像以及新出现/扩大的T2加权像病灶）：整个队列（n = 249），并根据既往治疗情况（醋酸格拉替雷/干扰素β-1[免疫调节剂]、那他珠单抗、未治疗过）、性别、基础EDSS评分、基础钆增强病灶、治疗前年复发率（ARR）、开始治疗时的年龄以及既往治疗次数进行分层。使用多变量模型评估ARR与基线特征的关系。还描述了安全性概况（不良事件[AEs]）。在整个队列、既往接受过免疫调节治疗的患者以及未治疗过的患者中，芬戈莫德使年化复发率（ARR）分别降低了75%、67%和85%（所有病例p<0.0001）。然而，既往接受过那他珠单抗治疗的患者ARR保持不变。ARR结果以及无复发患者比例的相应增加与开始治疗时的年龄、既往治疗次数、性别和基础钆增强病灶无关。尽管无论基础EDSS评分和芬戈莫德治疗前的ARR如何，芬戈莫德均有效，但在基础EDSS评分<3（0.2对0.4；p = 0.0244）以及芬戈莫德治疗前ARR≥2的患者中观察到了更好的结果（p = 0.0338）。在多变量模型中，仅基础EDSS评分与芬戈莫德治疗的前24个月内ARR相关（p = 0.0439）。整个队列中残疾进展的累积概率在第24个月时为20%，且与既往治疗、开始治疗时的年龄、既往治疗次数、性别、基础EDSS评分、基础钆增强病灶以及治疗前ARR无关。本研究中观察到的芬戈莫德在现实世界中的益处似乎与先前临床试验中观察到的相似。
