scholarly journals Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

2004 ◽  
Vol 10 (2) ◽  
pp. 139-144 ◽  
Author(s):  
M Clanet ◽  
L Kappos ◽  
H-P Hartung ◽  
R Hohlfeld ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Efficacy ◽  
Neutralizing Antibody ◽  
Disability Progression ◽  
Double Blind ◽  
Treatment Groups ◽  
Clinical Endpoints ◽  
Treatment Objective

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48% and 43%, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years.

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.

Long-term follow-up of patients treated with glatiramer acetate: a multicentre, multinational extension of the European/Canadian double-blind, placebo-controlled, MRI-monitored trial

2007 ◽  
Vol 13 (4) ◽  
pp. 502-508 ◽  
Author(s):  
M. Rovaris ◽  
G. Comi ◽  
MA Rocca ◽  
P. Valsasina ◽  
D. Ladkani ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Brain Mri ◽  
Treatment Phase ◽  
Double Blind ◽  
Brain Volumes ◽  
Disease Evolution ◽  
Long Term Follow Up

Glatiramer acetate (GA) is effective in reducing clinical and magnetic resonance imaging (MRI) activity in relapsing-remitting multiple sclerosis (RRMS). Serial long-term MRI data are lacking for large cohorts of GA-treated patients. The European/Canadian GA study consisted of two consecutive phases, each lasting nine months. The first treatment phase was randomized, double-blind and placebo-controlled. The second was an open-label, active treatment phase with daily administration of 20 mg GA subcutaneously for all patients. For the long-term follow-up (LTFU), dual echo, pre- and postgadolinium T1-weighted brain MRI scans were obtained with the same acquisition scheme as for the original trial and a neurological assessment was performed. Lesion volumes, normalized brain volumes and percentage brain volume changes (PBVC) were measured. One hundred and forty-two (63.4%) of the 224 patients who completed the two phases of the European/Canadian study underwent the LTFU after a mean period of 5.8 years (range: 5.3-6.4); 73 were treated with GA from study initiation. MRI measures at LTFU did not significantly differ between patients originally assigned to placebo and those who were always treated with GA, but the proportion of patients who did not require walking aids at LTFU was lower in the latter group (P=0.034). PBVC between baseline and LTFU was significantly correlated with lesion load at study entry. An earlier initiation of GA treatment in patients with active RRMS might, at least partially, have a favourable impact on long-term disease evolution. Multiple Sclerosis 2007; 13: 502-508. http://msj.sagepub.com

scholarly journals Serum contactin-1 as a biomarker of long-term disease progression in natalizumab-treated multiple sclerosis

2021 ◽  
pp. 135245852110100
Author(s):  
Zoë YGJ van Lierop ◽  
Luuk Wieske ◽  
Marleen JA Koel-Simmelink ◽  
Madhurima Chatterjee ◽  
Iris Dekker ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Odds Ratio ◽  
Prognostic Biomarker ◽  
Disability Progression ◽  
Lower Baseline ◽  
Relapsing Remitting ◽  
Natalizumab Treatment

Background: Natalizumab treatment provides a model for non-inflammation-induced disease progression in multiple sclerosis (MS). Objective: To study serum contactin-1 (sCNTN1) as a novel biomarker for disease progression in natalizumab-treated relapsing-remitting MS (RRMS) patients. Methods: Eighty-nine natalizumab-treated RRMS patients with minimum follow-up of 3 years were included. sCNTN1 was analyzed at baseline (before natalizumab initiation), 3, 12, 24 months (M) and last follow-up (median 5.2 years) and compared to 222 healthy controls (HC) and 15 primary progressive MS patients (PPMS). Results were compared between patients with progressive, stable, or improved disability according to EDSS-plus criteria. Results: Median sCNTN1 levels (ng/mL,) in RRMS (baseline: 10.7, 3M: 9.7, 12M: 10.4, 24M: 10.8; last follow-up: 9.7) were significantly lower compared to HC (12.5; p ⩽ 0.001). It was observed that 48% of patients showed progression during follow-up, 11% improved, and 40% remained stable. sCNTN1 levels were significantly lower in progressors both at baseline and at 12M compared to non-progressors. A 1 ng/mL decrease in baseline sCNTN1 was consistent with an odds ratio of 1.23 (95% confidence interval 1.04–1.45) ( p = 0.017) for progression during follow-up. Conclusion: Lower baseline sCNTN1 concentrations were associated with long-term disability progression during natalizumab treatment, making it a possible blood-based prognostic biomarker for RRMS.

scholarly journals CSF Chitinase 3–Like 2 Is Associated With Long-term Disability Progression in Patients With Progressive Multiple Sclerosis

2021 ◽  
Vol 8 (6) ◽  
pp. e1082
Author(s):  
Manuel Comabella ◽  
Jaume Sastre-Garriga ◽  
Eva Borras ◽  
Luisa M. Villar ◽  
Albert Saiz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Binding Protein ◽  
Area Under The Curve ◽  
Shotgun Proteomics ◽  
Progressive Multiple Sclerosis ◽  
Disability Progression ◽  
Protein Biomarkers ◽  
Discovery Cohort

ObjectiveThis study aimed to identify long-term prognostic protein biomarkers associated with disease progression in patients with progressive multiple sclerosis (MS).MethodsCSF samples were collected from a discovery cohort of 28 patients with progressive MS who participated in a clinical trial with interferon beta. Patients were classified into high and low disability progression phenotypes according to numeric progression rates (NPR) and step-based progression rates (SPR) after a mean follow-up time of 12 years. Protein abundance was measured by shotgun proteomics. Selected proteins from the discovery cohort were quantified by parallel reaction monitoring in CSF samples from an independent validation cohort of 41 patients with progressive MS classified also into high and low disability progression phenotypes after a mean follow-up time of 7 years.ResultsOf 2,548 CSF proteins identified in the discovery cohort, 10 were selected for validation based on their association with long-term disability progression: SPATS2-like protein, chitinase 3–like 2 (CHI3L2), plasma serine protease inhibitor, metallothionein-3, phospholipase D4, beta-hexosaminidase, neurexophilin-1, adipocyte enhancer-binding protein 1, cathepsin L1, and lipopolysaccharide-binding protein. Only CHI3L2 was validated, and patients with high disability progression exhibited significantly higher CSF protein levels compared with patients with low disability progression (p = 0.03 for NPR and p = 0.02 for SPR). CHI3L2 levels showed good performance to discriminate between high and low disability progression in patients with progressive MS (area under the curve 0.73; sensitivity 90% and specificity 63%).ConclusionsAlthough further confirmatory studies are needed, we propose CSF CHI3L2 as a prognostic protein biomarker associated with long-term disability progression in patients with progressive MS.Classification of EvidenceThis study provides Class II evidence that high CSF CHI3L2 levels identified higher disability progression in patients with progressive MS.

scholarly journals Characterizing Long-term Disability Progression and Employment in NARCOMS Registry Participants with Multiple Sclerosis Taking Dimethyl Fumarate

2021 ◽  
Author(s):  
Amber Salter ◽  
Samantha Lancia ◽  
Gary Cutter ◽  
Robert J. Fox ◽  
Ruth Ann Marrie ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Employment Status ◽  
Dimethyl Fumarate ◽  
Long Term Effects ◽  
Disability Progression ◽  
Research Committee ◽  
Work Related ◽  
Secondary Progressive

Abstract Background: Delayed-release dimethyl fumarate (DMF) is effective in relapsing-remitting multiple sclerosis (RRMS), but long-term effects of DMF on disability and disease progression in clinical settings are unknown. We evaluated disability and employment outcomes in persons with RRMS treated with DMF for up to 5 years. Methods: This longitudinal study included US North American Research Committee on Multiple Sclerosis (NARCOMS) Registry participants with RRMS reporting DMF initiation in fall 2013 through spring 2018 with 1 year or more of follow-up. Time to 6-month confirmed disability progression (≥1-point increase in Patient-Determined Disease Steps [PDDS] scale score) and change in employment status were evaluated using Kaplan-Meier analysis. Participants were censored at last follow-up or at DMF discontinuation, whichever came first. Results: During the study, 725 US participants with RRMS had at least 1 year of DMF follow-up data, of whom most were female and White. At year 5, 69.9% (95% CI, 65.4%–73.9%) of these participants were free from 6-month confirmed disability progression, and 84.7% (95% CI, 78.6%–89.2%) were free from conversion to secondary progressive MS. Of 116 participants with data at baseline and year 5, most had stable or improved PDDS scale and Performance Scales scores over 5 years. Of 322 participants 62 years and younger and employed at the index survey, 66.0% (95% CI, 57.6%–73.1%) were free from a negative change in employment type over 5 years. Conclusions: Most US NARCOMS Registry participants treated up to 5 years with DMF remained free from 6-month confirmed disability progression and conversion to secondary progressive MS and had stable disability and employment status. These results support the long-term stability of disability and work-related outcomes with disease-modifying therapy.

scholarly journals Evolution of tumefactive lesions in multiple sclerosis: A 12-year study with serial imaging in a single patient

2013 ◽  
Vol 19 (11) ◽  
pp. 1539-1543 ◽  
Author(s):  
Vasiliki N Ikonomidou ◽  
Nancy D Richert ◽  
Alexander Vortmeyer ◽  
Fernanda Tovar-Moll ◽  
Bibiana Bielekova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetization Transfer ◽  
Magnetic Resonance Images ◽  
Single Patient ◽  
Disability Progression ◽  
Term Evolution ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

We describe the acute presentation and the long-term evolution of recurrent tumefactive lesions (TLs) in a patient with relapsing–remitting multiple sclerosis. Five TLs occurred on three different occasions over a period of 12 years and these were followed by 73 serial magnetic resonance images (MRI). TL evolution was described by means of magnetization transfer imaging (MTI) and cerebrospinal fluid tissue specific imaging (TSI) over the follow-up period. During the study period, the patient had three clinical relapses with only minimal disability progression. MTI demonstrated that only the peripheral portion of each TL reverted to pre-lesional MT ratios within six months’ post-enhancement. Recurring TLs may present a similar pattern of evolution that may be associated with a long-term favourable clinical outcome.

EARLY PREDICTION OF LONG-TERM RESPONSE TO NATALIZUMAB IN MULTIPLE SCLEROSIS

2015 ◽  
Vol 86 (11) ◽  
pp. e4.22-e4
Author(s):  
Joel Raffel ◽  
Arie Gafson ◽  
Samer Dahdaleh ◽  
Richard Nicholas
Keyword(s):  
Multiple Sclerosis ◽  
Post Treatment ◽  
Clinical Activity ◽  
First Year ◽  
Disability Progression ◽  
Long Term Follow Up ◽  
Observational Cohort ◽  
Term Response

IntroductionIn people with multiple sclerosis treated with interferon-beta or glatiramer acetate, new MRI lesions and relapses during the first year of treatment predict poor prognosis. However, this association has not been studied in those receiving natalizumab.MethodologyData were collected on early relapses and new MRI activity from an observational cohort of 161 patients on natalizumab, with long-term follow-up. Two outcome measures were used. The first – ‘Clinical Activity Years 1–3’ – defined non-responders as those with relapses or EDSS progression at years 1–3 post-treatment, versus baseline. The second – ‘Disability Progression Years 3+’ – defined non-responders as those with EDSS progression at 3–7 years post-treatment, versus baseline.Results‘Clinical Activity Years 1–3’ was strongly predicted by early relapses (Odds Ratio (OR) 8.4, p<0.0001), and by a combined score of early relapses and MRI activity (Modified Rio Score 1: OR 4.9, p<0.001. Modified Rio Score 2: OR 19.0, P<0.01). In contrast, ‘Disability Progression Years 3+’ was not predicted by early relapses or MRI activity.ConclusionsRelapses and new MRI activity within the first year of starting natalizumab predict short-term outcomes, but not long-term disability outcomes. This requires further validation in other cohorts.

scholarly journals Rituximab versus mitoxantrone: comparing effectiveness and safety in advanced relapsing multiple sclerosis

2021 ◽  
Vol 12 ◽  
pp. 204062232110243
Author(s):  
Zrzavy Tobias ◽  
Daniels Esther ◽  
Stuka Niklas ◽  
Weber Dennis ◽  
Winkelmann Alexander ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Propensity Score ◽  
Adverse Events ◽  
Lower Probability ◽  
Disability Progression ◽  
Treatment Groups ◽  
Off Label ◽  
Favorable Safety ◽  
Relapsing Multiple Sclerosis

Background: Rituximab (RTX), a CD20 depleting agent, is a frequently used off-label treatment for multiple sclerosis (MS), while mitoxantrone (MTX) is approved, albeit rarely used for active relapsing MS (RMS). However, observational data comparing RTX and MTX effectiveness and safety are scarce. Objective: We aimed to compare effectiveness and safety of MTX and RTX in patients with active RMS. Methods: From combined retrospective clinical data of three MS centers, we selected patients who had received at least one infusion of RTX or MTX and had at least a 6-month clinical follow-up available. Treatment groups were compared by propensity score (PS)-adjusted regression and inverse PS-weighted generalized estimated equation models regarding disability progression, relapse activity, and adverse events (AEs). Results: We included 292 RMS patients (mean age 41.8 years, 71.6% female) who received RTX (119 patients, mean age 36.8 years, 74.8% female) or MTX (173 patients mean age 45.3 years, 69.4% female). Using both PS methods, we did not find a significant effect favoring RTX or MTX treatment regarding the probability of disability worsening or relapse occurrence. However, RTX treatment was associated with a significantly lower probability of severe AEs and AEs. Conclusions: RTX shows comparable effectiveness but a favorable safety profile compared with MTX in active RMS.

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

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