Ospedale San Raffaele, Via Olgettina 58, 20132, Milan, Italy.
University of Ottawa and The Ottawa Hospital Research Institute, 501 Smyth Rd, Box, Ottawa, ON, 601, Canada.
BMC Neurol. 2020 Oct 6;20(1):364. doi: 10.1186/s12883-020-01937-4.
In this pooled, post hoc analysis of a phase 2 trial and the phase 3 TEMSO, TOWER, and TENERE clinical trials, long-term efficacy and safety of teriflunomide were assessed in subgroups of patients with relapsing multiple sclerosis (MS) defined by prior treatment status.
Patients were classified according to their prior treatment status in the core and core plus extension periods. In the core period, patients were grouped according to treatment status at the start of the study: treatment naive (no prior disease-modifying therapy [DMT] or DMT > 2 years prior to randomization), previously treated with another DMT (DMT > 6 to ≤24 months prior to randomization), and recently treated with another DMT (DMT ≤6 months prior to randomization). In the core plus extension period, patients were re-baselined to the time of starting teriflunomide 14 mg and grouped according to prior treatment status at that time point. Efficacy endpoints included annualized relapse rate (ARR), probability of confirmed disability worsening (CDW) over 12 weeks, and Expanded Disability Status Scale (EDSS) score. The incidence of adverse events was also assessed.
Most frequently received prior DMTs at baseline were glatiramer acetate and interferon beta-1a across treatment groups. Teriflunomide 14 mg significantly reduced ARR versus placebo in the core period, regardless of prior treatment status. In the core and extension periods, adjusted ARRs were low (0.193-0.284) in patients treated with teriflunomide 14 mg across all subgroups. Probability of CDW by Year 4 was similar across subgroups; by Year 5, the percentage of patients with 12-week CDW was similar in treatment-naive patients and patients recently treated with another DMT (33.9 and 33.7%, respectively). EDSS scores were stable over time in all prior-treatment subgroups. There were no new or unexpected safety signals. Limitations include selective bias due to patient attrition, variability in subgroup size, and lack of magnetic resonance imaging outcomes.
The efficacy and safety of teriflunomide 14 mg was similar in all patients with relapsing MS, regardless of prior treatment history.
Phase 2 trial core: NCT01487096 ; Phase 2 trial extension: NCT00228163 ; TEMSO core: NCT00134563 ; TEMSO extension: NCT00803049 ; TOWER: NCT00751881 ; TENERE: NCT00883337 .
在这项 2 期试验和 3 期 TEMSO、TOWER 和 TENERE 临床试验的事后分析中，评估了特立氟胺在复发型多发性硬化症（MS）患者亚组中的长期疗效和安全性，这些患者根据先前的治疗情况进行了定义。
根据核心和核心加扩展期间的先前治疗情况对患者进行分类。在核心期间，根据研究开始时的治疗情况对患者进行分组：治疗初治（无先前疾病修饰治疗[DMT]或随机化前 DMT>2 年）、先前用另一种 DMT 治疗（随机化前 DMT>6 至≤24 个月）和最近用另一种 DMT 治疗（随机化前 DMT≤6 个月）。在核心加扩展期间，患者重新以开始特立氟胺 14mg 的时间为基线，并根据该时间点的先前治疗情况进行分组。疗效终点包括年化复发率（ARR）、12 周时确认残疾恶化（CDW）的概率和扩展残疾状态量表（EDSS）评分。还评估了不良事件的发生率。
基线时最常接受的先前 DMT 是各组中的那他珠单抗和干扰素β-1a。特立氟胺 14mg 与安慰剂相比，在核心期间显著降低了 ARR。在核心和扩展期间，在所有亚组中，接受特立氟胺 14mg 治疗的患者的调整后 ARR 较低（0.193-0.284）。第 4 年时，各组的 CDW 发生率相似；第 5 年时，治疗初治患者和最近接受另一种 DMT 治疗的患者中，12 周 CDW 的患者比例相似（分别为 33.9%和 33.7%）。所有先前治疗亚组的 EDSS 评分随时间稳定。没有新的或意外的安全信号。局限性包括由于患者流失导致的选择性偏倚、亚组大小的变异性以及缺乏磁共振成像结果。
特立氟胺 14mg 的疗效和安全性在所有复发型多发性硬化症患者中相似，无论其先前的治疗史如何。
2 期试验核心：NCT01487096；2 期试验扩展：NCT00228163；TEMSO 核心：NCT00134563；TEMSO 扩展：NCT00803049；TOWER：NCT00751881；TENERE：NCT00883337。
