University of Toronto, Toronto, ON, Canada.
N Engl J Med. 2011 Oct 6;365(14):1293-303. doi: 10.1056/NEJMoa1014656.
Teriflunomide is a new oral disease-modifying therapy for relapsing forms of multiple sclerosis.
We concluded a randomized trial involving 1088 patients with multiple sclerosis, 18 to 55 years of age, with a score of 0 to 5.5 on the Expanded Disability Status Scale and at least one relapse in the previous year or at least two relapses in the previous 2 years. Patients were randomly assigned (in a 1:1:1 ratio) to placebo, 7 mg of teriflunomide, or 14 mg of teriflunomide once daily for 108 weeks. The primary end point was the annualized relapse rate, and the key secondary end point was confirmed progression of disability for at least 12 weeks.
Teriflunomide reduced the annualized relapse rate (0.54 for placebo vs. 0.37 for teriflunomide at either 7 or 14 mg), with relative risk reductions of 31.2% and 31.5%, respectively (P<0.001 for both comparisons with placebo). The proportion of patients with confirmed disability progression was 27.3% with placebo, 21.7% with teriflunomide at 7 mg (P=0.08), and 20.2% with teriflunomide at 14 mg (P=0.03). Both teriflunomide doses were superior to placebo on a range of end points measured by magnetic resonance imaging (MRI). Diarrhea, nausea, and hair thinning were more common with teriflunomide than with placebo. The incidence of elevated alanine aminotransferase levels (≥1 times the upper limit of the normal range) was higher with teriflunomide at 7 mg and 14 mg (54.0% and 57.3%, respectively) than with placebo (35.9%); the incidence of levels that were at least 3 times the upper limit of the normal range was similar in the lower- and higher-dose teriflunomide groups and the placebo group (6.3%, 6.7%, and 6.7%, respectively). Serious infections were reported in 1.6%, 2.5%, and 2.2% of patients in the three groups, respectively. No deaths occurred.
Teriflunomide significantly reduced relapse rates, disability progression (at the higher dose), and MRI evidence of disease activity, as compared with placebo. (Funded by Sanofi-Aventis; TEMSO ClinicalTrials.gov number, NCT00134563.).
特立氟胺是一种新的多发性硬化症缓解型口服疾病修正治疗药物。
我们进行了一项随机试验，纳入了 1088 名年龄在 18 至 55 岁之间、扩展残疾状况量表评分为 0 至 5.5 分且过去 1 年有 1 次复发或过去 2 年有 2 次以上复发的多发性硬化症患者。患者被随机分配（1:1:1 比例）至安慰剂组、7mg 特立氟胺组或 14mg 特立氟胺组，每日 1 次，共 108 周。主要终点为年化复发率，关键次要终点为确认残疾进展至少 12 周。
特立氟胺降低了年化复发率（安慰剂组为 0.54，7mg 或 14mg 特立氟胺组分别为 0.37），相对风险降低分别为 31.2%和 31.5%（与安慰剂相比均 P<0.001）。安慰剂组、7mg 特立氟胺组和 14mg 特立氟胺组中确认残疾进展的患者比例分别为 27.3%、21.7%（P=0.08）和 20.2%（P=0.03）。特立氟胺组在一系列磁共振成像（MRI）测量的终点上均优于安慰剂组。特立氟胺组比安慰剂组更常见腹泻、恶心和头发稀疏。7mg 和 14mg 特立氟胺组丙氨酸氨基转移酶水平升高（≥正常值上限 1 倍）的发生率分别为 54.0%和 57.3%，高于安慰剂组的 35.9%（P<0.001）；而丙氨酸氨基转移酶水平升高至少 3 倍于正常值上限的发生率在低剂量和高剂量特立氟胺组及安慰剂组之间相似（分别为 6.3%、6.7%和 6.7%）。三组患者中分别有 1.6%、2.5%和 2.2%报告严重感染。无死亡病例。
与安慰剂相比，特立氟胺显著降低了复发率、残疾进展（高剂量组）和 MRI 疾病活动证据。（由赛诺菲-安万特资助；TEMSO 临床试验.gov 编号，NCT00134563）。
