University of British Columbia Hospital Multiple Sclerosis Clinic, Vancouver, BC, Canada.
Lancet Neurol. 2012 May;11(5):420-8. doi: 10.1016/S1474-4422(12)70056-X. Epub 2012 Apr 10.
Fingolimod 0·5 mg once daily is approved for treatment of relapsing multiple sclerosis (MS). In the phase 3, 2-year FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in MS) study, fingolimod significantly reduced annualised relapse rates (ARRs) and the risk of confirmed disability progression compared with placebo. We aimed to investigate whether the beneficial treatment effect reported for the overall population is consistent in subgroups of patients with different baseline characteristics.
We did subgroup analyses of ARRs (primary outcome) and confirmed disability progression (a secondary outcome) over 24 months in the FREEDOMS study, a randomised, double-blind study that included 1272 patients with relapsing-remitting MS who were assigned 1:1:1 to fingolimod (0·5 mg or 1·25 mg) or placebo once daily for 24 months. Subgroups were predefined, predefined and slightly modified, or defined post hoc, by demographic factors (including sex and age), disease characteristics (including baseline disability scores, relapse rates, and lesion parameters), and response to previous therapy (including analyses in patients eligible for fingolimod treatment according to the European label). Data were analysed by intention to treat. The FREEDOMS study is registered with ClinicalTrials.gov, number NCT00289978.
Treatment with fingolimod 0·5 mg was associated with significantly lower ARRs versus placebo across all subgroups except for patients aged over 40 years. ARR ratios ranged from 0·76 (95% CI 0·54-1·09; p=0·13) in patients aged over 40 years to 0·29 (0·16-0·52; p<0·0001) in patients who had relapse activity despite receiving interferon beta during the year before study enrolment. Hazard ratios for confirmed disability progression over 24 months with fingolimod 0·5 mg versus placebo ranged from 0·85 (95% CI 0·53-1·36; p=0·50) in patients with a T2 lesion volume of 3300 mm(3) or less to 0·32 (0·14-0·73; p=0·0066) in patients with an EDSS over 3·5. In patients who relapsed and had lesion activity despite treatment with interferon beta in the previous year, the ARR ratio for fingolimod 0·5 mg versus placebo was 0·38 (95% CI 0·21-0·68, p=0·0011), and for treatment-naive patients with rapidly evolving severe disease it was 0·33 (0·18-0·62, p=0·0006). Hazard ratios for confirmed disability progression over 24 months were 0·68 (0·29-1·62; p=0·39) and 0·73 (0·25-2·07; p=0·55), respectively, in these groups.
Patients with relapsing-remitting MS with a wide spectrum of clinical and MRI features including subgroups specified by the European label can potentially benefit from treatment with 0·5 mg fingolimod.
Novartis.
每日一次的芬戈莫德 0.5 毫克已获批准用于治疗复发性多发性硬化症（MS）。在 3 期 FREEDOMS（FTY720 Research Evaluating Effects of Daily Oral therapy in MS）研究中，与安慰剂相比，芬戈莫德显著降低了年复发率（ARR）和确诊残疾进展的风险。我们旨在调查在不同基线特征的患者亚组中，报告的总体人群的有益治疗效果是否一致。
我们对 FREEDOMS 研究中的 ARR（主要结局）和 24 个月内确诊残疾进展（次要结局）进行了亚组分析，这是一项随机、双盲研究，纳入了 1272 例复发缓解型 MS 患者，按 1:1:1 的比例随机分配至芬戈莫德（0.5 毫克或 1.25 毫克）或安慰剂，每日一次，持续 24 个月。亚组是根据人口统计学因素（包括性别和年龄）、疾病特征（包括基线残疾评分、复发率和病变参数）以及先前治疗的反应（包括根据欧洲标签符合芬戈莫德治疗条件的患者分析）预先定义、预先定义和稍作修改或事后定义的。数据分析采用意向治疗。FREEDOMS 研究在 ClinicalTrials.gov 注册，编号为 NCT00289978。
除年龄超过 40 岁的患者外，与安慰剂相比，每日 0.5 毫克芬戈莫德治疗与所有亚组的 ARR 显著降低。ARR 比值范围为年龄超过 40 岁的患者为 0.76（95%CI 0.54-1.09；p=0.13）至接受干扰素β治疗的患者在研究入组前一年仍有复发活动的患者为 0.29（0.16-0.52；p<0.0001）。与安慰剂相比，24 个月时使用 0.5 毫克芬戈莫德治疗的患者发生确诊残疾进展的风险比范围为 T2 病变体积为 3300mm3 或更小的患者为 0.85（95%CI 0.53-1.36；p=0.50）至 EDSS 超过 3.5 的患者为 0.32（0.14-0.73；p=0.0066）。在过去一年中因复发而接受干扰素β治疗且仍有病变活动的患者中，0.5 毫克芬戈莫德与安慰剂的 ARR 比值为 0.38（95%CI 0.21-0.68，p=0.0011），而对于治疗初发且病情迅速恶化的患者，ARR 比值为 0.33（0.18-0.62，p=0.0006）。在这两个组中，24 个月时确诊残疾进展的风险比分别为 0.68（0.29-1.62；p=0.39）和 0.73（0.25-2.07；p=0.55）。
具有广泛临床和 MRI 特征的复发缓解型 MS 患者，包括欧洲标签规定的亚组，可能受益于 0.5 毫克芬戈莫德治疗。
诺华公司。
