دورية أكاديمية
أعرض في EDS

Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose-ranging study.

التفاصيل البيبلوغرافية
العنوان: Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose-ranging study.
المؤلفون: Fang T; King's College London, Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, UK., Al Khleifat A; King's College London, Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, UK., Meurgey JH; King's College London, Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, UK., Jones A; King's College London, Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, UK., Leigh PN; Department of Neurology, Brighton and Sussex Medical School, Sussex, UK., Bensimon G; Department of Pharmacology, Hôpital Pitié-Salpêtrière, Paris, France., Al-Chalabi A; King's College London, Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, UK; King's College Hospital, Denmark Hill, London, UK. Electronic address: ammar.al-chalabi@kcl.ac.uk.
المصدر: The Lancet. Neurology [Lancet Neurol] 2018 May; Vol. 17 (5), pp. 416-422. Date of Electronic Publication: 2018 Mar 07.
نوع المنشور: Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Lancet Pub. Group Country of Publication: England NLM ID: 101139309 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-4465 (Electronic) Linking ISSN: 14744422 NLM ISO Abbreviation: Lancet Neurol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London, UK ; New York, NY : Lancet Pub. Group, 2002-
مواضيع طبية MeSH: Disease Progression* , Outcome Assessment, Health Care* , Severity of Illness Index* , Survival Analysis*, Amyotrophic Lateral Sclerosis/*drug therapy , Excitatory Amino Acid Antagonists/*administration & dosage , Riluzole/*administration & dosage, Amyotrophic Lateral Sclerosis/mortality ; Dose-Response Relationship, Drug ; Humans ; Retrospective Studies ; Time Factors
مستخلص: Background: Riluzole is the only drug to prolong survival for amyotrophic lateral sclerosis (ALS) and, at a dose of 100 mg, was associated with a 35% reduction in mortality in a clinical trial. A key question is whether the survival benefit occurs at an early stage of disease, late stage, or is spread throughout the course of the disease. To address this question, we used the King's clinical staging system to do a retrospective analysis of data from the original dose-ranging clinical trial of riluzole.
Methods: In the original dose-ranging trial, patients were enrolled between December, 1992, and November, 1993, in Belgium, France, Germany, Spain, Canada, the USA, and the UK if they had probable or definite ALS as defined by the El Escorial criteria. The censor date for the riluzole survival data was set as the original study end date of Dec 31, 1994. For this analysis, King's clinical ALS stage was estimated from the electronic case record data of the modified Norris scale, UK Medical Research Council score for muscle strength, El Escorial category, vital capacity, and gastrostomy insertion data. The lowest allocated stage was 2 because the original trial only included patients with probable or definite ALS. We used a χ 2 test to assess the independence of stage at trial enrolment and treatment group, Kaplan-Meier product limit distribution to test the transition from each stage to subsequent stages, and Cox regression to confirm an effect of treatment group on time in stage, controlling for covariates. We did sensitivity analyses by combining treatment groups, using alternative strategies to stage, stratifying by stage at trial enrolment, and using multistate outcome analysis of treatments (MOAT).
Findings: We analysed the case records of all 959 participants from the original dose-ranging trial, 237 assigned to 50 mg/day riluzole, 236 to 100 mg/day, 244 to 200 mg/day, and 242 to daily placebo. Clinical stage at enrolment did not significantly differ between treatment groups (p=0·22). Time in stage 4 was longer for patients receiving 100 mg/day riluzole than for those receiving placebo (hazard ratio [HR] 0·55, 95% CI 0·36-0·83; log-rank p=0·037). Combining treatment groups and stratifying by stage at enrolment showed a similar result (HR 0·638, 95% CI 0·464-0·878; p=0·006), as did analysis with MOAT where the mean number of days spent in stage 4 was numerically higher for patients given riluzole at higher doses compared with patients receiving placebo. Time from stages 2 or 3 to subsequent stages or death did not differ between riluzole treatment groups and placebo (p=0·83 for stage 2 and 0·88 for stage 3).
Interpretation: We showed that riluzole prolongs survival in the last clinical stage of ALS; this finding needs to be confirmed in a prospective study, and treatment effects at stage 1 still need to be analysed. The ALS stage at which benefit occurs is important for counselling of patients before starting treatment. Staging should be used in future ALS clinical trials to assess the stage at which survival benefit occurs, and a similar approach could be used for other neurodegenerative diseases.
Funding: NIHR Maudsley Biomedical Research Centre, The European Union Joint Programme on Neurodegeneration, and the King's Summer Undergraduate Studentship.
(Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
التعليقات: Comment in: Lancet Neurol. 2018 May;17(5):385-386. (PMID: 29525493)
Comment in: Lancet Neurol. 2018 Jul;17(7):579. (PMID: 29914701)
Comment in: Lancet Neurol. 2018 Jul;17(7):579-580. (PMID: 29914702)
References: Mol Psychiatry. 2016 Feb;21(2):237-42. (PMID: 25778474)
Amyotroph Lateral Scler Frontotemporal Degener. 2014 Jun;15(3-4):279-84. (PMID: 24720420)
J Neurol Neurosurg Psychiatry. 2006 Mar;77(3):390-2. (PMID: 16484652)
Lancet. 1996 Sep 21;348(9030):795-9. (PMID: 8813989)
J Neurol. 2010 Oct;257(10):1713-7. (PMID: 20532545)
J Neurol Neurosurg Psychiatry. 2015 Jan;86(1):45-9. (PMID: 24463480)
J Neurol Neurosurg Psychiatry. 2016 Dec;87(12 ):1361-1367. (PMID: 27378085)
Health Technol Assess. 2001;5(2):1-97. (PMID: 11809124)
Lancet Neurol. 2016 Oct;15(11):1182-94. (PMID: 27647646)
Arch Neurol. 1998 Apr;55(4):526-8. (PMID: 9561981)
Nat Rev Neurol. 2016 Nov;12 (11):651-661. (PMID: 27658852)
Neurology. 2009 Nov 17;73(20):1681-5. (PMID: 19917991)
Brain. 2012 Mar;135(Pt 3):847-52. (PMID: 22271664)
Lancet Neurol. 2013 Apr;12(4):339-45. (PMID: 23453347)
Lancet. 1996 May 25;347(9013):1425-31. (PMID: 8676624)
J Neurol. 2002 May;249(5):609-15. (PMID: 12021952)
J Neurol. 2003 Apr;250(4):473-9. (PMID: 12700914)
Amyotroph Lateral Scler Frontotemporal Degener. 2013 Apr;14(3):162-8. (PMID: 23323713)
Int J Biostat. 2016 May 1;12 (1):45-63. (PMID: 27227717)
J Neurol Sci. 1999 Oct 31;169(1-2):13-21. (PMID: 10540002)
J Neurol Neurosurg Psychiatry. 2015 Jan;86(1):38-44. (PMID: 24336810)
N Engl J Med. 2016 Nov 10;375(19):1845-1855. (PMID: 27717298)
Lancet Neurol. 2013 Nov;12(11):1059-67. (PMID: 24067398)
Amyotroph Lateral Scler Frontotemporal Degener. 2014 Sep;15(5-6):376-87. (PMID: 24597488)
Amyotroph Lateral Scler Frontotemporal Degener. 2015 Jun;16(3-4):202-8. (PMID: 25646865)
JAMA Neurol. 2016 Jul 1;73(7):812-20. (PMID: 27244217)
N Engl J Med. 1994 Mar 3;330(9):585-91. (PMID: 8302340)
J Neurol Neurosurg Psychiatry. 2008 Jan;79(1):33-7. (PMID: 17550991)
Amyotroph Lateral Scler. 2012 Oct;13(6):555-9. (PMID: 22871077)
معلومات مُعتمدة: ALCHALABI-TALBOT/APR14/926-794 United Kingdom MNDA_ Motor Neurone Disease Association; JONES/OCT15/958-799 United Kingdom MNDA_ Motor Neurone Disease Association; MR/R024804/1 United Kingdom MRC_ Medical Research Council; MR/L501529/1 United Kingdom MRC_ Medical Research Council
المشرفين على المادة: 0 (Excitatory Amino Acid Antagonists)
7LJ087RS6F (Riluzole)
تواريخ الأحداث: Date Created: 20180312 Date Completed: 20190315 Latest Revision: 20210109
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5899963
DOI: 10.1016/S1474-4422(18)30054-1
PMID: 29525492
قاعدة البيانات: MEDLINE
الوصف
تدمد:1474-4465
DOI:10.1016/S1474-4422(18)30054-1