Is the Symbol Digit Modalities Test a useful outcome in secondary progressive multiple sclerosis?
demyelinating diseases
multiple sclerosis
neurological disorders
randomized clinical trial
research methods
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
10
01
2021
received:
22
11
2020
accepted:
11
01
2021
pubmed:
16
1
2021
medline:
13
8
2021
entrez:
15
1
2021
Statut:
ppublish
Résumé
It is unclear which cognitive outcome measure is the most useful for clinical trials in multiple sclerosis. To investigate the usefulness of the Symbol Digit Modalities Test (SDMT) as a clinical outcome measure in secondary progressive multiple sclerosis (SPMS), we describe the frequency of worsening and improvement events in a large randomized controlled trial (RCT) dataset. Using original trial data from the ASCEND trial (n = 889), a recent large RCT in SPMS, we describe worsening and similarly defined improvement with and without 3-month confirmation on the SDMT in the whole trial cohort and unconfirmed worsening and improvement on the Paced Auditory Serial Addition Test (PASAT) in a smaller subset (n = 107). Somewhat unexpectedly, SDMT scores steadily increased throughout the 2 years of follow-up in this trial. There were overall few SDMT worsening events throughout the trial (generally fewer than 10% of participants), but improvement events steadily increased from around 50% of participants with improvement at 12 weeks to more than 70% at 84 weeks and beyond. PASAT scores followed a similar pattern. In this well-characterized clinical trial cohort, the SDMT does not reflect the steady cognitive decline that patients with SPMS experience. Both SDMT and PASAT scores improve throughout follow-up, possibly due to a practice effect. The SDMT may not be a useful outcome measure of disease progression in 2-year clinical trials in SPMS.
Sections du résumé
BACKGROUND
It is unclear which cognitive outcome measure is the most useful for clinical trials in multiple sclerosis. To investigate the usefulness of the Symbol Digit Modalities Test (SDMT) as a clinical outcome measure in secondary progressive multiple sclerosis (SPMS), we describe the frequency of worsening and improvement events in a large randomized controlled trial (RCT) dataset.
METHODS
Using original trial data from the ASCEND trial (n = 889), a recent large RCT in SPMS, we describe worsening and similarly defined improvement with and without 3-month confirmation on the SDMT in the whole trial cohort and unconfirmed worsening and improvement on the Paced Auditory Serial Addition Test (PASAT) in a smaller subset (n = 107).
RESULTS
Somewhat unexpectedly, SDMT scores steadily increased throughout the 2 years of follow-up in this trial. There were overall few SDMT worsening events throughout the trial (generally fewer than 10% of participants), but improvement events steadily increased from around 50% of participants with improvement at 12 weeks to more than 70% at 84 weeks and beyond. PASAT scores followed a similar pattern.
CONCLUSIONS
In this well-characterized clinical trial cohort, the SDMT does not reflect the steady cognitive decline that patients with SPMS experience. Both SDMT and PASAT scores improve throughout follow-up, possibly due to a practice effect. The SDMT may not be a useful outcome measure of disease progression in 2-year clinical trials in SPMS.
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
2115-2120Informations de copyright
© 2021 European Academy of Neurology.
Références
Rao SM, Leo GJ, Ellington L, Nauertz T, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology. 1991;41:692-696.
Planche V, Gibelin M, Cregut D, Pereira B, Clavelou P. Cognitive impairment in a population-based study of patients with multiple sclerosis: differences between late relapsing-remitting, secondary progressive and primary progressive multiple sclerosis. Eur J Neurol. 2016;23:282-289.
Tombaugh TN. A comprehensive review of the Paced Auditory Serial Addition Test (PASAT). Arch Clin Neuropsychol. 2006;21:53-76.
Strober L, DeLuca J, Benedict RH, et al. Symbol Digit Modalities Test: a valid clinical trial endpoint for measuring cognition in multiple sclerosis. Mult Scler J Houndmills Basingstoke Engl. 2019;25:1781-1790.
Morrow SA, Drake A, Zivadinov R, Munschauer F, Weinstock-Guttman B, Benedict RHB. Predicting loss of employment over three years in multiple sclerosis: clinically meaningful cognitive decline. Clin Neuropsychol. 2010;24:1131-1145.
Kapoor R, Ho P-R, Campbell N, et al. Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension. Lancet Neurol. 2018;17:405-415.
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444-1452.
R Development Core Team. R: A language and environment for statistical computing [online]. Vienna, Austria: R Foundation for Statistical Computing; 2020. Accessed at: http://www.R-project.org/
Koch MW, Mostert J, Uitdehaag B, Cutter G. Clinical outcome measures in SPMS trials: an analysis of the IMPACT and ASCEND original trial data sets. Mult Scler J 2020;26:1540-1549.
Feinstein A, Brown R, Ron M. Effects of practice of serial tests of attention in healthy subjects. J Clin Exp Neuropsychol. 1994;16:436-447.
Benedict RHB, Tomic D, Cree BA, et al. Siponimod and cognition in secondary progressive multiple sclerosis: EXPAND secondary analyses. Neurology; 2021;96:e376-e386.
Benedict RH, Cohan S, Lynch SG, et al. Improved cognitive outcomes in patients with relapsing-remitting multiple sclerosis treated with daclizumab beta: results from the DECIDE study. Mult Scler J Houndmills Basingstoke Engl. 2018;24:795-804.