Effect of fingolimod on MRI outcomes in patients with paediatric-onset multiple sclerosis: results from the phase 3 PARADIGMS study.,Journal of Neurology, Neurosurgery, and Psychiatry

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Effect of fingolimod on MRI outcomes in patients with paediatric-onset multiple sclerosis: results from the phase 3 PARADIGMS study.
Journal of Neurology, Neurosurgery, and Psychiatry ( IF 8.7 ) Pub Date : 2020-03-04 , DOI: 10.1136/jnnp-2019-322138
Douglas L Arnold _{1,

2} , Brenda Banwell ₃ , Amit Bar-Or _{4,

5} , Angelo Ghezzi ₆ , Benjamin M Greenberg ₇ , Emmanuelle Waubant ₈ , Gavin Giovannoni ₉ , Jerry S Wolinsky ₁₀ , Jutta Gärtner ₁₁ , Kevin Rostásy ₁₂ , Lauren Krupp ₁₃ , Marc Tardieu ₁₄ , Wolfgang Brück ₁₅ , Tracy E Stites ₁₆ , Gregory L Pearce ₁₇ , Dieter A Häring ₁₈ , Martin Merschhemke ₁₈ , Tanuja Chitnis ₁₉ ,

Affiliation

Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
NeuroRx Research, Montreal, Quebec, Canada.
The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Perelman School of Medicine, University of Pennsylvania, Philadephia, Pennsylvania, USA, Montreal, Quebec, Canada.
Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada, Philadephia, Pennsylvania, USA.
Centro Studi Sclerosi Multipla, Ospedale di Gallarate, Gallarate, Italy.
Department of Neurology and Neurotherapeutics, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Department of Neurology, University of California, San Francisco, California, USA.
Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, UK.
McGovern Medical School, Department of Neurology, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA, Houston, Texas, USA.
Department of Paediatrics and Adolescent Medicine, German Centre for Multiple Sclerosis in Childhood and Adolescence, University Medical Centre, Göttingen, Germany.
Division of Paediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany.
Department of Neurology; Pediatric MS Center, NYU Langone Health, New York, NY USA, USA, New York, USA.
Hôpitaux universitaires Paris Sud, Paediatric Neurology Department, Assistance Publique-Hôpitaux de Paris, Paris France, Paris, France.
Department of Neuropathology, University Medical Centre, Göttingen, Germany.
Neuroscience TA, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
GCE Solutions, Bloomington, Illinois, USA.
Neuroscience TA, Novartis Pharma AG, Basel, Switzerland.
Partners Pediatric Multiple Sclerosis Center, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.

OBJECTIVE PARADIGMS demonstrated superior efficacy and comparable safety of fingolimod versus interferon β-1a (IFN β-1a) in paediatric-onset multiple sclerosis (PoMS). This study aimed to report all predefined MRI outcomes from this study. METHODS Patients with multiple sclerosis (MS) (aged 10-<18 years) were randomised to once-daily oral fingolimod (n=107) or once-weekly intramuscular IFN β-1a (n=108) in this flexible duration study. MRI was performed at baseline and every 6 months for up to 2 years or end of the study (EOS) in case of early treatment discontinuation/completion. Key MRI endpoints included the annualised rate of formation of new/newly enlarging T2 lesions, gadolinium-enhancing (Gd+) T1 lesions, new T1 hypointense lesions and combined unique active (CUA) lesions (6 months onward), changes in T2 and Gd+ T1 lesion volumes and annualised rate of brain atrophy (ARBA). RESULTS Of the randomised patients, 107 each were treated with fingolimod and IFN β-1a for up to 2 years. Fingolimod reduced the annualised rate of formation of new/newly enlarging T2 lesions (52.6%, p<0.001), number of Gd+ T1 lesions per scan (66.0%, p<0.001), annualised rate of new T1 hypointense lesions (62.8%, p<0.001) and CUA lesions per scan (60.7%, p<0.001) versus IFN β-1a at EOS. The percent increases from baseline in T2 (18.4% vs 32.4%, p<0.001) and Gd+ T1 (-72.3% vs 4.9%, p=0.001) lesion volumes and ARBA (-0.48% vs -0.80%, p=0.014) were lower with fingolimod versus IFN β-1a, the latter partially due to accelerated atrophy in the IFN β-1a group. CONCLUSION Fingolimod significantly reduced MRI activity and ARBA for up to 2 years versus IFN β-1a in PoMS.

中文翻译：

芬戈莫德对小儿发作多发性硬化症患者MRI结局的影响：PARADIGMS 3期研究的结果。

目的性研究证明芬戈莫德相对于干扰素β-1a（IFNβ-1a）在儿科多发性硬化症（PoMS）中具有更高的疗效和相当的安全性。本研究旨在报告该研究中所有预定义的MRI结果。方法在这个灵活的持续时间研究中，将多发性硬化症（MS）（10- <18岁）患者随机分为每日一次口服芬戈莫德（n = 107）或每周一次肌内IFNβ-1a（n = 108）。在早期治疗中断/完成的情况下，在基线和每6个月进行MRI长达2年或研究结束（EOS）。MRI的主要终点指标包括：新/新扩大的T2病变，g增强（Gd +）T1病变，新的T1低点性病变和合并的独特活动性（CUA）病变的年形成率（自6个月起），T2和Gd + T1病变体积的变化以及脑萎缩的年化率（ARBA）。结果在随机分组的患者中，每人107例接受芬戈莫德和IFNβ-1a治疗长达2年。芬戈莫德降低了新的/新扩大的T2病变的年形成率（52.6％，p <0.001），每次扫描的Gd + T1病变的数量（66.0％，p <0.001），新的T1低点病变的年化率（62.8％，与EOS时的IFNβ-1a相比，每次扫描的CUA病变（p <0.001）和CUA病变（60.7％，p <0.001）。T2（18.4％vs 32.4％，p <0.001）和Gd + T1（-72.3％vs 4.9％，p = 0.001）病变量和ARBA（-0.48％vs -0.80％，p = 0.014）相对于基线的百分比增加芬戈莫德与IFNβ-1a相比降低了，后者部分归因于IFNβ-1a组的萎缩加速。

更新日期：2020-05-01

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