Department of Pediatric Neurology, National Referral Center for Rare Inflammatory Brain and Spinal Diseases, Hopitaux Universitaires Paris-Sud, Le Kremlin-Bicetre, France
Immunology of Viral Infections and Autoimmune Diseases, Universite Paris 11 Faculte de Medecine, Le Kremlin-Bicetre, France.
J Neurol Neurosurg Psychiatry. 2020 Jan;91(1):58-66. doi: 10.1136/jnnp-2019-321124. Epub 2019 Aug 29.
In PARADIG, a double-blind phase III trial in 215 paediatric patients with multiple sclerosis (MS) (10 to <18 years), fingolimod administered for up to 2 years significantly reduced the annualised relapse rate (ARR) and rate of new/newly enlarged T2 (n/neT2) lesions compared with interferon (IFN) β-1a.
To investigate (1) differences between treatment groups across subpopulations (treatment-naïve, younger/prepubertal patients); (2) disability progression.
ARRs at 10, 11 and 12 years were estimated based on predefined modelling extrapolations. Changes in Expanded Disability Status Scale (EDSS), and in 3 month (3M) and 6 month (6M) confirmed disability progression (CDP) were evaluated post hoc.
In the treatment-naïve subpopulation, fingolimod reduced ARR and n/neT2 lesions by 85.8% and 53.4%, respectively versus INF β-1a (both p<0.001), compared with 81.9% and 52.6% in the overall population. Model-based ARR reductions in younger patients (≤12 years) were 91.9%-94.6%. Twice as many IFN β-1a-treated than fingolimod-treated patients had worse EDSS scores at study end (20.6% vs 10.5%, p=0.043). Risk reductions in 3M-CDP and 6M-CDP were 77.2% (p=0.007) and 80.2% (p=0.040), respectively.
Fingolimod in paediatric MS was associated with consistent control of disease activity versus IFN β-1a (including treatment-naïve and younger patients) and resulted in less disability progression for up to 2 years.
NCT01892722.
在 PARADIG 试验中，215 名多发性硬化症（MS）儿科患者（年龄为 10 至<18 岁）接受了为期 2 年的双盲 III 期临床试验，与干扰素（IFN）β-1a 相比， fingolimod 可显著降低年复发率（ARR）和新/新扩大 T2（n/neT2）病变的发生率。
研究（1）治疗组在亚组人群（初治患者、年轻/青春期前患者）中的差异；（2）残疾进展。
基于预设模型外推，估计 10、11 和 12 年的 ARR。事后评估扩展残疾状况量表（EDSS）以及 3 个月（3M）和 6 个月（6M）确认的残疾进展（CDP）的变化。
在初治亚组中，fingolimod 与 IFN β-1a 相比，ARR 和 n/neT2 病变分别降低了 85.8%和 53.4%（均 p<0.001），而总体人群中分别降低了 81.9%和 52.6%。年轻患者（≤12 岁）的模型预测 ARR 降低了 91.9%-94.6%。与 fingolimod 治疗组相比，接受 IFN β-1a 治疗的患者中，在研究结束时 EDSS 评分恶化的患者人数增加了一倍（20.6%比 10.5%，p=0.043）。3M-CDP 和 6M-CDP 的风险降低分别为 77.2%（p=0.007）和 80.2%（p=0.040）。
在儿科多发性硬化症患者中，fingolimod 与 IFN β-1a 相比可持续控制疾病活动（包括初治患者和年轻患者），并在长达 2 年内导致残疾进展减少。
NCT01892722。
