scholarly journals Baseline EDSS proportions in MS clinical trials affect the overall outcome and power: A cautionary note

2016 ◽  
Vol 23 (7) ◽  
pp. 982-987 ◽  
Author(s):  
Guoqiao Wang ◽  
Gary R Cutter ◽  
Stacey S Cofield ◽  
Fred Lublin ◽  
Jerry S Wolinsky ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Progression Rate ◽  
Disability Progression ◽  
Cautionary Note ◽  
Trial Outcome ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Event Rates ◽  
Relapsing Remitting Multiple Sclerosis

Background: In randomized clinical trials, when treatments do not work equally effectively across stratifications of participants, observed event rates may differ from those hypothesized leading to deviations in estimated power. Objectives: To investigate the effect of distributions of baseline Expanded Disability Status Scale (EDSS) proportions in relapsing-remitting multiple sclerosis (RRMS) on the trial outcome, confirmed disability progression rate (CDPR), and power. Methods: We reported CDPRs in the CombiRx trial by baseline EDSS and by groups (1st (0, 1), 2nd (1.5, 2), 3rd (2.5, 3), and 4th (⩾3.5)) and investigated the effect of different combinations of baseline EDSS proportions on the trial outcome and power. Results: There were 244 (25.4%) participants in the 1st group, 368 (38.4%) in the 2nd group, 223 (23.3%) in the 3rd group, and 124 (12.9%) in the 4th group with CDPRs of 40.1%, 13.9%, 11.2%, and 16.9%, respectively. Both CDPR and power increased when the proportion of the 1st group increased in hypothetical trials with equal sample sizes in each arm, and a 10% increase in the 1st group led to a 5% increase in power. Conclusion: Various baseline EDSS proportions yielded different CDPRs and power, suggesting caution in interpretation of treatment effects across trials that enrolled participants with different proportions of baseline EDSS.

Relationship between Sustained Disability Progression and Functional System Scores in Relapsing-Remitting Multiple Sclerosis: Analysis of Placebo Data from Four Randomized Clinical Trials

2015 ◽  
Vol 44 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Thomas Scott ◽  
Ping Wang ◽  
Xiaojun You ◽  
Monica Mann ◽  
Bjørn Sperling
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Functional System ◽  
Validity And Reliability ◽  
Disability Progression ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

Background: The Expanded Disability Status Scale (EDSS), based on different functional system scores (FSS), remains the most frequently used disability assessment in relapsing-remitting multiple sclerosis (RRMS). In this analysis, we evaluated the relationship between sustained disability progression, measured by EDSS, and simultaneous changes in individual FSS domains. Methods: A post hoc analysis was performed on data from placebo-treated RRMS patients from four large, randomized, multicenter, phase 3 clinical trials. Sustained disability progression was defined as a ≥1.0-point EDSS score increase over a ≥3- or ≥6-month period. Simultaneous sustained disability progression and worsening of individual FSS domains was analyzed. Results: The majority of patients experienced sustained disability progression and simultaneous worsening of ≥1 FSS domain, with ≥1-point worsening in the pyramidal domain being most frequently associated with sustained disability progression (in 31-51% of patients), followed by ≥1-point worsening in the cerebellar (35-41% of patients) and sensory (31-45% of patients) domains. Conclusion: The key FSS components correlating with sustained disability progression, measured by EDSS, appear to be pyramidal, cerebellar, and sensory. In this analysis, the simultaneous worsening of consistent FSS domains confirms the validity and reliability of the use of sustained EDSS progression as a measure of disability progression.

scholarly journals Greater sensitivity to multiple sclerosis disability worsening and progression events using a roving versus a fixed reference value in a prospective cohort study

2017 ◽  
Vol 24 (7) ◽  
pp. 963-973 ◽  
Author(s):  
Ludwig Kappos ◽  
Helmut Butzkueven ◽  
Heinz Wiendl ◽  
Timothy Spelman ◽  
Fabio Pellegrini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Reference Value ◽  
Cumulative Probability ◽  
Baseline Score ◽  
Disability Progression ◽  
Open Label ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Fixed Reference ◽  
Relapsing Remitting Multiple Sclerosis

Background: Confirmed Expanded Disability Status Scale (EDSS) progression occurring after a fixed-study entry baseline is a common measure of disability increase in relapsing-remitting multiple sclerosis (RRMS) studies but may not detect all disability progression events, especially those unrelated to overt relapses. Objective: To evaluate possible measures of disability progression unrelated to relapse using EDSS data over ≈5.5 years from the Tysabri® Observational Program (TOP). Methods: TOP is an ongoing, prospective, open-label study in RRMS patients receiving intravenous 300 mg natalizumab every 4 weeks. Measures of increasing disability were assessed using as a reference either study baseline score or a “roving” system that resets the reference score after ⩾24- or ⩾48-week confirmation of a new score. Results: This analysis included 5562 patients. Approximately 70% more EDSS progression events unrelated to relapse and 50% more EDSS worsening events overall were detected with a roving reference score (cumulative probability: 17.6% and 29.7%, respectively) than with a fixed reference baseline score (cumulative probability: 10.1% and 20.3%, respectively). Conclusion: In this long-term observational RRMS dataset, a roving EDSS reference value was more efficient than a study baseline EDSS reference in detecting progression/worsening events unrelated to relapses and thus the transition to secondary progressive disease.

Multimodal evoked potentials measure and predict disability progression in early relapsing–remitting multiple sclerosis

2008 ◽  
Vol 14 (4) ◽  
pp. 553-556 ◽  
Author(s):  
P Jung ◽  
A Beyerle ◽  
U Ziemann
Keyword(s):  
Multiple Sclerosis ◽  
Early Stage ◽  
Expanded Disability Status Scale ◽  
Disability Progression ◽  
Multiple Sclerosis Functional Composite ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Multimodal Evoked Potentials ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

In 37 patients with early relapsing–remitting multiple sclerosis (RRMS), a multimodal EP score (mEPS) and clinical scores (Expanded Disability Status Scale (EDSS) and multiple sclerosis functional composite (MSFC)) were obtained prospectively over 24 months. Changes in mEPS correlated with changes in EDSS (Spearman’s ρ = 0.69, p < 0.0001) and MSFC (ρ = –0.41, p < 0.02). Patients with relevant EDSS progression ( n = 7) showed stronger mEPS deterioration than clinically stable patients (10.8 ± 3.2 versus 1.3 ± 0.8, p < 0.005). Baseline mEPS was not significantly correlated with baseline EDSS but with EDSS after 24 months (ρ = 0.39, p < 0.02). The data suggest that serial mEPS measure and moderately predict clinically relevant disease activity in the therapeutically most relevant early stage of RRMS.

scholarly journals Relationship between Expanded Disability Status Scale scores and the presence of temporomandibular disorders in patients with multiple sclerosis

2018 ◽  
Vol 12 (01) ◽  
pp. 144-148 ◽  
Author(s):  
Lucas Senra Correa Carvalho ◽  
Osvaldo José Moreira Nascimento ◽  
Luciane Lacerda Franco Rocha Rodrigues ◽  
Andre Palma Da Cunha Matta
Keyword(s):  
Multiple Sclerosis ◽  
Temporomandibular Disorders ◽  
Control Group ◽  
Expanded Disability Status Scale ◽  
Exact Test ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Scale Scores ◽  
Axis I ◽  
Relapsing Remitting Multiple Sclerosis

ABSTRACTObjectives: The objectives of this study were to assess the prevalence of temporomandibular disorders (TMDs) in patients with relapsing-remitting multiple sclerosis (MS) and to investigate whether an association exists between the presence of TMD symptoms and the degree of MS-related disability. Materials and Methods: In all, 120 individuals were evaluated: 60 patients with a diagnosis of relapsing-remitting MS and 60 age- and sex-matched controls without neurological impairments. A questionnaire recommended by the European Academy of Craniomandibular Disorders for the assessment of TMD symptoms was administered. For those who answered affirmatively to at least one of the questions, the RDC/TMD Axis I instrument was used for a possible classification of TMD subtypes. The Expanded Disability Status Scale (EDSS) was the measure of the degree of MS-related disability. Statistical Analysis Used: Fisher’s exact test was used to analyze the data. ANOVA was used to detect significant differences between means and to assess whether the factors influenced any of the dependent variables by comparing means from the different groups. Results: The prevalence of TMD symptoms in patients with MS was 61.7% versus 18.3% in the control group (CG). A diagnosis of TMD was established for 36.7% in the MS group and 3.3% in the CG (P = 0.0001). There were statistically significant differences between degrees of MS-related disability and the prevalence of TMD (P = 0.0288). Conclusions: The prevalence of both TMD and TMD symptoms was significantly greater in the MS group. EDSS scores and TMD prevalence rates were inversely related.

scholarly journals Assessment of Disability Progression Independent of Relapse and Brain MRI Activity in Patients with Multiple Sclerosis in Poland

2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Katarzyna Kapica-Topczewska ◽  
François Collin ◽  
Joanna Tarasiuk ◽  
Agata Czarnowska ◽  
Monika Chorąży ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Activity ◽  
Brain Mri ◽  
Disability Progression ◽  
Program Monitoring ◽  
Therapeutic Program ◽  
Relapsing Remitting ◽  
Second Year ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

The aim of the study was to verify the association of clinical relapses and brain activity with disability progression in relapsing/remitting multiple sclerosis patients receiving disease-modifying treatments in Poland. Disability progression was defined as relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and progression independent of relapses and brain MRI Activity (PIRMA). Data from the Therapeutic Program Monitoring System were analyzed. Three panels of patients were identified: R0, no relapse during treatment, and R1 and R2 with the occurrence of relapse during the first and the second year of treatment, respectively. In the R0 panel, we detected 4.6% PIRA patients at 24 months (p < 0.001, 5.0% at 36 months, 5.6% at 48 months, 6.1% at 60 months). When restricting this panel to patients without brain MRI activity, we detected 3.0% PIRMA patients at 12 months, 4.5% at 24 months, and varying from 5.3% to 6.2% between 36 and 60 months of treatment, respectively. In the R1 panel, RAW was detected in 15.6% patients at 12 months and, in the absence of further relapses, 9.7% at 24 months and 6.8% at 36 months of treatment. The R2 group was associated with RAW significantly more frequently at 24 months compared to the R1 at 12 months (20.7%; p < 0.05), but without a statistical difference later on. In our work, we confirmed that disability progression was independent of relapses and brain MRI activity.

Parity and disability progression in relapsing–remitting multiple sclerosis

2020 ◽  
Vol 267 (12) ◽  
pp. 3753-3762
Author(s):  
Anat Achiron ◽  
◽  
Alon Ben-David ◽  
Michael Gurevich ◽  
David Magalashvili ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disability Progression ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis
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