scholarly journals Siponimod and Cognition in Secondary Progressive Multiple Sclerosis

Neurology ◽  
2020 ◽  
Vol 96 (3) ◽  
pp. e376-e386 ◽  
Author(s):  
Ralph H.B. Benedict ◽  
Davorka Tomic ◽  
Bruce A. Cree ◽  
Robert Fox ◽  
Gavin Giovannoni ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Processing ◽  
Processing Speed ◽  
Lower Risk ◽  
Controlled Trial ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Significant Benefit ◽  
Secondary Progressive ◽  
Cognitive Processing Speed

ObjectiveTo investigate the effects of siponimod on cognitive processing speed in patients with secondary progressive (SP) multiple sclerosis (MS), by means of a predefined exploratory and post hoc analysis of the Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND) study, a randomized controlled trial comparing siponimod and placebo.MethodsEXPAND was a double-blind, placebo-controlled phase 3 trial involving 1,651 patients with SPMS randomized (2:1) to either siponimod 2 mg/d or placebo. Cognitive function was assessed with the Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Brief Visuospatial Memory Test–Revised (BVMT-R) administered at baseline, 6-month intervals, and end of treatment.ResultsBetween-group differences in mean change from baseline in SDMT scores were significantly better in siponimod- vs placebo-treated patients at month 12 (difference 1.08 [95% confidence interval 0.23–1.94]; p = 0.0132), month 18 (1.23 [0.25–2.21); p = 0.0135), and month 24 (2.30 [1.11–3.50]; p = 0.0002). Siponimod-treated patients were at significantly lower risk for having a 4-point sustained decrease in SDMT score (hazard ratio [HR] 0.79 [0.65–0.96]; p = 0.0157), while their chance for having a 4-point sustained increase in SDMT score was higher (HR 1.28 [1.05–1.55]; p = 0.0131). PASAT and BVMT-R scores did not differ significantly between the 2 treatment groups (all p > 0.28).ConclusionSiponimod had a significant benefit on SDMT in patients with SPMS. Siponimod-treated patients were at significantly lower risk for having a ≥4-point decrease in SDMT score and had a significantly higher chance for having a ≥4-point increase in SDMT score, a magnitude of change accepted as clinically meaningful.ClinicalTrials.gov IdentifierNCT01665144.Classification of EvidenceThis study provides Class II evidence that, for patients with SPMS, siponimod had a significant benefit on cognitive processing speed.

scholarly journals A 10-year follow-up of the European multicenter trial of interferon β-1b in secondary-progressive multiple sclerosis

2015 ◽  
Vol 22 (4) ◽  
pp. 533-543 ◽  
Author(s):  
J Kuhle ◽  
M Hardmeier ◽  
G Disanto ◽  
K Gugleta ◽  
M Ecsedi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Controlled Trial ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Analysis Of Covariance ◽  
Long Term Effects ◽  
Long Term Outcome ◽  
Secondary Progressive

Objectives: To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b). Methods: We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied. Results: Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R2: 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited ( R2: 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability. Conclusions: The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.

Reliability of Outcome Measures in Clinical Trials in Secondary Progressive Multiple Sclerosis

Neurology ◽  
2020 ◽  
Vol 96 (1) ◽  
pp. e111-e120 ◽  
Author(s):  
Marcus W. Koch ◽  
Jop Mostert ◽  
Pavle Repovic ◽  
James D. Bowen ◽  
Bernard Uitdehaag ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Outcome Measures ◽  
Controlled Trial ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Disability Progression ◽  
Secondary Progressive ◽  
Randomized Controlled ◽  
Disability Status ◽  
Over Time

ObjectiveTo investigate the reliability of clinical outcomes in secondary progressive multiple sclerosis (SPMS) trials, we compared the frequency of progression and improvement events on different clinical outcome measures in the placebo arms of 2 large randomized controlled trial (RCT) datasets.MethodsUsing original trial data from the placebo arms of IMPACT (International MS Secondary Progressive Avonex Controlled Trial) and ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis), 2 large RCTs in SPMS, we compared disability progression and similarly defined improvement with and without 3- or 6-month confirmation on the outcome measures Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and their combinations.ResultsIn both datasets, the EDSS showed the highest rates of improvement over time, and the smallest difference between progression and improvement rates, followed by the T25FW and the 9HPT. For the T25FW and 9HPT, improvement rates were fairly stable over time and remained at below or around the 10% level. For the EDSS, improvement rates increased in parallel with disability progression rates.ConclusionsAll investigated outcome measures in SPMS showed some evidence of random variation and measurement error, the T25FW and 9HPT less so than the more established outcome EDSS. Our findings are relevant for the design and critical appraisal of trials in SPMS.

MRI brain volume loss, lesion burden, and clinical outcome in secondary progressive multiple sclerosis

2021 ◽  
pp. 135245852110318
Author(s):  
Marcus W Koch ◽  
Jop Mostert ◽  
Pavle Repovic ◽  
James D Bowen ◽  
Eva Strijbis ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Volume ◽  
Controlled Trial ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Cognitive Disability ◽  
Volume Loss ◽  
Secondary Progressive ◽  
T2 Lesions ◽  
Brain Volume Loss

Background: Magnetic resonance imaging (MRI) of brain volume measures are widely used outcomes in secondary progressive multiple sclerosis (SPMS), but it is unclear whether they are associated with physical and cognitive disability. Objective: To investigate the association between MRI outcomes and physical and cognitive disability worsening in people with SPMS. Methods: We used data from ASCEND, a large randomized controlled trial ( n = 889). We investigated the association of change in whole brain and gray matter volume, contrast enhancing lesions, and T2 lesions with significant worsening on the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (NHPT), and Symbol Digit Modalities Test (SDMT) with logistic regression models. Results: We found no association between MRI measures and EDSS or SDMT worsening. T25FW worsening at 48 and 96 weeks, and NHPT worsening at 96 weeks were associated with cumulative new or newly enlarging T2 lesions at 96 weeks. NHPT worsening at 48 and 96 weeks was associated with normalized brain volume loss at 48 weeks, but not with other MRI outcomes. Conclusion: The association of standard MRI outcomes and disability was noticeably weak and inconsistent over 2 years of follow-up. These MRI outcomes may not be useful surrogates of disability measures in SPMS.

Intravenous immunoglobulin in secondary progressive multiple sclerosis: randomised placebo-controlled trial

The Lancet ◽  
2004 ◽  
Vol 364 (9440) ◽  
pp. 1149-1156 ◽  
Author(s):  
Otto R Hommes ◽  
Per S Sørensen ◽  
Franz Fazekas ◽  
Monika Maas Enriquez ◽  
Hans W Koelmel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Intravenous Immunoglobulin ◽  
Controlled Trial ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Secondary Progressive
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