Association of Age With Contrast-Enhancing Lesions Across the Multiple Sclerosis Disease Spectrum.
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
28 09 2021
28 09 2021
Historique:
received:
23
04
2021
accepted:
20
07
2021
pubmed:
12
8
2021
medline:
30
10
2021
entrez:
11
8
2021
Statut:
ppublish
Résumé
To investigate the association of age and the presence of contrast-enhancing lesions (CELs) on cranial MRI scans in different disease courses of multiple sclerosis (MS), we describe the frequency of CELs as a function of age in 4 large randomized controlled trial (RCT) datasets. Using original trial data from CombiRx (Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis; clinicaltrials.gov identifier NCT00211887), a trial in relapsing-remitting MS; ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis; clinicaltrials.gov identifier NCT01416181), a trial in secondary progressive MS; and the 2 primary progressive MS trials PROMISE and INFORMS; clinicaltrials.gov identifier NCT00731692), we describe the occurrence of CELs per age group at baseline for the entire trial cohort and at 1 year follow-up in the treatment arms. CombiRx included 1,008, ASCEND 889, PROMISE 943, and INFORMS 970 participants. At baseline, CEL frequency differed between datasets according to disease course: 39.6% of CombiRx, 23.9% of ASCEND, 14.0% of PROMISE, and 12.3% of INFORMS participants had CELs. This distribution by disease course was largely preserved within each age group. In all datasets, there was an almost linear decrease of the percentage of participants with CELs with advancing age. After 1 year of experimental treatment, CEL occurrence was reduced in all trial datasets, and almost absent in ASCEND. The decrease of CEL occurrence with advancing age was preserved in CombiRx, PROMISE, and INFORMS after 1 year of treatment. We investigated the association of the baseline factors age, disease duration, sex, and EDSS with having CELs at baseline with multivariable binary logistic regression models. Age was the only characteristic associated with the risk of CELs at baseline in all datasets, with higher age associated with a lower risk of CELs (odds ratios for having CELs at baseline per year increase in age: CombiRx: 0.96, 95% confidence interval [CI] 0.95-0.98; ASCEND: 0.94, 95% CI 0.92-0.97; PROMISE: 0.94, 95% CI 0.91-0.96; INFORMS: 0.97, 95% CI 0.94-0.99). Our analysis of 4 large, well-characterized RCT datasets shows that the association of age and CEL occurrence is a general phenomenon across the spectrum of MS disease courses. Our findings should be replicated in real-world MS datasets.
Sections du résumé
BACKGROUND AND OBJECTIVES
To investigate the association of age and the presence of contrast-enhancing lesions (CELs) on cranial MRI scans in different disease courses of multiple sclerosis (MS), we describe the frequency of CELs as a function of age in 4 large randomized controlled trial (RCT) datasets.
METHODS
Using original trial data from CombiRx (Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis; clinicaltrials.gov identifier NCT00211887), a trial in relapsing-remitting MS; ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis; clinicaltrials.gov identifier NCT01416181), a trial in secondary progressive MS; and the 2 primary progressive MS trials PROMISE and INFORMS; clinicaltrials.gov identifier NCT00731692), we describe the occurrence of CELs per age group at baseline for the entire trial cohort and at 1 year follow-up in the treatment arms.
RESULTS
CombiRx included 1,008, ASCEND 889, PROMISE 943, and INFORMS 970 participants. At baseline, CEL frequency differed between datasets according to disease course: 39.6% of CombiRx, 23.9% of ASCEND, 14.0% of PROMISE, and 12.3% of INFORMS participants had CELs. This distribution by disease course was largely preserved within each age group. In all datasets, there was an almost linear decrease of the percentage of participants with CELs with advancing age. After 1 year of experimental treatment, CEL occurrence was reduced in all trial datasets, and almost absent in ASCEND. The decrease of CEL occurrence with advancing age was preserved in CombiRx, PROMISE, and INFORMS after 1 year of treatment. We investigated the association of the baseline factors age, disease duration, sex, and EDSS with having CELs at baseline with multivariable binary logistic regression models. Age was the only characteristic associated with the risk of CELs at baseline in all datasets, with higher age associated with a lower risk of CELs (odds ratios for having CELs at baseline per year increase in age: CombiRx: 0.96, 95% confidence interval [CI] 0.95-0.98; ASCEND: 0.94, 95% CI 0.92-0.97; PROMISE: 0.94, 95% CI 0.91-0.96; INFORMS: 0.97, 95% CI 0.94-0.99).
DISCUSSION
Our analysis of 4 large, well-characterized RCT datasets shows that the association of age and CEL occurrence is a general phenomenon across the spectrum of MS disease courses. Our findings should be replicated in real-world MS datasets.
Identifiants
pubmed: 34376508
pii: WNL.0000000000012603
doi: 10.1212/WNL.0000000000012603
pmc: PMC8589289
doi:
Banques de données
ClinicalTrials.gov
['NCT01416181', 'NCT00211887', 'NCT00731692']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1334-e1342Subventions
Organisme : NINDS NIH HHS
ID : U01 NS045719
Pays : United States
Informations de copyright
© 2021 American Academy of Neurology.
Références
Mult Scler. 2010 Mar;16(3):317-24
pubmed: 20203148
Nat Rev Neurosci. 2012 Jun 20;13(7):507-14
pubmed: 22714021
Lancet Neurol. 2018 May;17(5):405-415
pubmed: 29545067
N Engl J Med. 2018 Jan 11;378(2):169-180
pubmed: 29320652
Neurology. 2005 Nov 8;65(9):1447-54
pubmed: 16275834
Front Neurol. 2017 Nov 10;8:577
pubmed: 29176956
J Neurol Sci. 2005 Dec 15;239(1):95-9
pubmed: 16209877
Ann Neurol. 1983 Mar;13(3):227-31
pubmed: 6847134
Nat Rev Neurol. 2012 Nov 5;8(11):647-56
pubmed: 23007702
J Neurol Neurosurg Psychiatry. 2005 Sep;76(9):1255-8
pubmed: 16107362
Neurology. 2000 May 9;54(9):1734-41
pubmed: 10802777
Neurology. 1983 Nov;33(11):1444-52
pubmed: 6685237
Ann Neurol. 2001 Jul;50(1):121-7
pubmed: 11456302
J Neurol. 2008 Mar;255 Suppl 1:3-11
pubmed: 18317671
J Neurol Neurosurg Psychiatry. 2008 Dec;79(12):1368-74
pubmed: 18535026
Lancet. 2016 Mar 12;387(10023):1075-1084
pubmed: 26827074
J Neurol. 2020 Sep;267(9):2619-2624
pubmed: 32388832
Ann Neurol. 2013 Mar;73(3):327-40
pubmed: 23424159
Ann Neurol. 2007 Jan;61(1):14-24
pubmed: 17262850
Ann Neurol. 2015 Nov;78(5):710-21
pubmed: 26239536