scholarly journals Improvement in relapse recovery with peginterferon beta-1a in patients with multiple sclerosis

2016 ◽  
Vol 2 ◽  
pp. 205521731667664 ◽  
Author(s):  
Thomas F Scott ◽  
Bernd C Kieseier ◽  
Scott D Newsome ◽  
Douglas L Arnold ◽  
Xiaojun You ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Effect ◽  
Disability Progression ◽  
Double Blind ◽  
Advance Study ◽  
Treatment Groups ◽  
Parallel Group ◽  
Relapsing Remitting ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

Background Subcutaneous peginterferon beta-1a every 2 weeks significantly affects clinical outcomes in patients with relapsing–remitting multiple sclerosis (RRMS). Objectives To explore relationships between relapses and worsening of disability in patients with RRMS, and assess the treatment effect of peginterferon beta-1a on relapse recovery. Methods Post-hoc analysis of the 2-year, randomized, double-blind, parallel-group, Phase 3 ADVANCE study. The severity of relapses, proportion of patients with relapses associated with residual disability (onset of 24-week confirmed disability progression (CDP) within 90 days following a relapse), and persistence of changes in Functional Systems Scores, were compared between treatment groups. Results Subcutaneous peginterferon beta-1a every 2 weeks significantly reduced the proportion of patients experiencing relapse associated with CDP over 2 years (6.6%, compared with 15.1% of patients who received placebo in Year 1; p = 0.02). Reduction in relapses associated with residual disability was greater than the treatment effect on overall relapse rate, and occurred despite similar relapse severity across treatment groups. Conclusions The beneficial effect of peginterferon beta-1a on risk of CDP may be attributable to the combination of an overall reduction in the risk of relapses and improvement in recovery from relapses, thus limiting further disability progression. Trial registration ClinicalTrials.gov identifier: NCT00906399

scholarly journals Consistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS

2019 ◽  
pp. jnnp-2019-321124 ◽  
Author(s):  
Kumaran Deiva ◽  
Peter Huppke ◽  
Brenda Banwell ◽  
Tanuja Chitnis ◽  
Jutta Gärtner ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Phase Iii ◽  
Disability Progression ◽  
Double Blind ◽  
Younger Patients ◽  
Treatment Groups ◽  
Registration Number ◽  
Treatment Naïve ◽  
Post Hoc

BackgroundIn PARADIGMS, a double-blind phase III trial in 215 paediatric patients with multiple sclerosis (MS) (10 to <18 years), fingolimod administered for up to 2 years significantly reduced the annualised relapse rate (ARR) and rate of new/newly enlarged T2 (n/neT2) lesions compared with interferon (IFN) β-1a.ObjectivesTo investigate (1) differences between treatment groups across subpopulations (treatment-naïve, younger/prepubertal patients); (2) disability progression.MethodsARRs at 10, 11 and 12 years were estimated based on predefined modelling extrapolations. Changes in Expanded Disability Status Scale (EDSS), and in 3 month (3M) and 6 month (6M) confirmed disability progression (CDP) were evaluated post hoc.ResultsIn the treatment-naïve subpopulation, fingolimod reduced ARR and n/neT2 lesions by 85.8% and 53.4%, respectively versus INF β-1a (both p<0.001), compared with 81.9% and 52.6% in the overall population. Model-based ARR reductions in younger patients (≤12 years) were 91.9%–94.6%. Twice as many IFN β-1a-treated than fingolimod-treated patients had worse EDSS scores at study end (20.6% vs 10.5%, p=0.043). Risk reductions in 3M-CDP and 6M-CDP were 77.2% (p=0.007) and 80.2% (p=0.040), respectively.ConclusionsFingolimod in paediatric MS was associated with consistent control of disease activity versus IFN β-1a (including treatment-naïve and younger patients) and resulted in less disability progression for up to 2 years.Trial registration numberNCT01892722.

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 Peginterferon beta-1a in multiple sclerosis: 2-year results from ADVANCE

2014 ◽  
Vol 21 (8) ◽  
pp. 1025-1035 ◽  
Author(s):  
Bernd C Kieseier ◽  
Douglas L Arnold ◽  
Laura J Balcer ◽  
Alexey A Boyko ◽  
Jean Pelletier ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Efficacy And Safety ◽  
Dosing Regimen ◽  
Disability Progression ◽  
Advance Study ◽  
Relapsing Remitting ◽  
Annualized Relapse Rate ◽  
Registration Number ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Risk Of Relapse

Objective: To evaluate the efficacy and safety of subcutaneous peginterferon beta-1a over 2 years in patients with relapsing–remitting multiple sclerosis in the ADVANCE study. Methods: Patients were randomized to placebo or 125 µg peginterferon beta-1a every 2 or 4 weeks. For Year 2 (Y2), patients originally randomized to placebo were re-randomized to peginterferon beta-1a every 2 weeks or every 4 weeks. Patients randomized to peginterferon beta-1a in Year 1 (Y1) remained on the same dosing regimen in Y2. Results: Compared with Y1, annualized relapse rate (ARR) was further reduced in Y2 with every 2 week dosing (Y1: 0.230 [95% CI 0.183–0.291], Y2: 0.178 [0.136–0.233]) and maintained with every 4 week dosing (Y1: 0.286 [0.231–0.355], Y2: 0.291 [0.231–0.368]). Patients starting peginterferon beta-1a from Y1 displayed improved efficacy versus patients initially assigned placebo, with reductions in ARR (every 2 weeks: 37%, p<0.0001; every 4 weeks: 17%, p=0.0906), risk of relapse (every 2 weeks: 39%, p<0.0001; every 4 weeks: 19%, p=0.0465), 12-week disability progression (every 2 weeks: 33%, p=0.0257; every 4 weeks: 25%, p=0.0960), and 24-week disability progression (every 2 weeks: 41%, p=0.0137; every 4 weeks: 9%, p=0.6243). Over 2 years, greater reductions were observed with every 2 week versus every 4 week dosing for all endpoints and peginterferon beta-1a was well tolerated. Conclusions: Peginterferon beta-1a efficacy is maintained beyond 1 year, with greater effects observed with every 2 week versus every 4 week dosing, and a similar safety profile to Y1. Clinicaltrials.gov Registration Number: NCT00906399.

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.

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