061 Ocrelizumab reduces disability progression independent of relapse activity in patients with relapsing multiple sclerosis (RMS) (ENCORE)

2018 ◽  
Vol 89 (6) ◽  
pp. A25.2-A25 ◽  
Author(s):  
Ludwig Kappos ◽  
Jerry S Wolinsky ◽  
Gavin Giovannoni ◽  
Douglas L Arnold ◽  
Fred Lublin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Subgroup Analysis ◽  
Interferon Beta ◽  
Expanded Disability Status Scale ◽  
Disability Progression ◽  
Intention To Treat ◽  
Secondary Progressive ◽  
Superior Efficacy ◽  
Disability Status ◽  
Relapsing Multiple Sclerosis

IntroductionOcrelizumab-(OCR) showed superior efficacy vs interferon beta-1a-(IFNβ1a) in OPERA I/II trials in RMS. Confirmed disability progression-(CDP) based on composite of Expanded Disability Status Scale-(EDSS), timed 25-foot walk-(T25FW) and 9-hole peg test-(9HPT) may better characterise aspects of disability progression than EDSS alone and has improved sensitivity for assessing progression in secondary progressive MS-(SPMS).MethodsRMS patients, including relapsing SPMS patients, in OPERA I/II-(NCT01247324/NCT01412333) received IV-OCR 600 mg (q24w) or SC-IFNβ1a 44 µg (tiw) over 96 weeks. CCDP was defined as disability progression measured by EDSS (increase ≥1.0 or 0.5 if baseline >5.5) or ≥20% T25FW increase or ≥20% 9 HPT increase, confirmed after ≥12/≥24 weeks. Definition-1 of CCDP-IRA=reference EDSS/T25FW/9HPT was re-baselined at first available assessment ≥30 days, after each relapse and no relapse should occur between baseline and initial disability progression [IDP], and within 30 days post-IDP and 30 days prior to IDP confirmation. Definition-2=period of no relapse for 30 days post-IDP confirmation. Subgroup analysis included patients at potentially higher SPMS risk based on baseline-EDSS ≥4.0 and pyramidal Kurtzke Functional Systems Score ≥2.ResultsIn the pooled intention-to-treat (ITT) cohort (n=1,656), risk reduction (RR; OCR vs IFNβ1a) for 12-/24 week CCDP was 34% (30.7% vs 21.5%; p<0.001) and 31% (22.6% vs 16.1%; p=0.002). The 12-/24 week CCDP-IRA RRs for Definition-1 were 24% (25.4% vs 19.6%; p=0.010) and 22% (19.2% vs 14.9%; p=0.046); and for Definition-2, 25% (25.4% vs 19.5%; p=0.008) and 23% (19.2% vs 14.8%; p=0.039). In the subgroup at higher SPMS risk, 12-/24 week RRs for CCDP-IRA (Definition-2) were 40% (31.2% vs 19.1%; p=0.022) and 36% (26.9% vs 16.6%; p=0.064). All CCDP-IRA components in the ITT and subgroups followed similar trends.ConclusionResults show that considerable disability progression in RMS occurs independently of protocol-defined relapses. Ocrelizumab significantly reduced progression vs IFNβ1a in the OPERA ITT population of RMS patients and more so in the subgroup at higher SPMS risk.

scholarly journals No evidence of disease activity (NEDA) analysis by epochs in patients with relapsing multiple sclerosis treated with ocrelizumab vs interferon beta-1a

2018 ◽  
Vol 4 (1) ◽  
pp. 205521731876064 ◽  
Author(s):  
Eva Havrdová ◽  
Douglas L Arnold ◽  
Amit Bar-Or ◽  
Giancarlo Comi ◽  
Hans-Peter Hartung ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Interferon Beta ◽  
Relative Increase ◽  
Disability Progression ◽  
T2 Lesions ◽  
Superior Efficacy ◽  
Intent To Treat ◽  
Relapsing Multiple Sclerosis ◽  
Treat Population

Background No evidence of disease activity (NEDA; defined as no 12-week confirmed disability progression, no protocol-defined relapses, no new/enlarging T2 lesions and no T1 gadolinium-enhancing lesions) using a fixed-study entry baseline is commonly used as a treatment outcome in multiple sclerosis (MS). Objective The objective of this paper is to assess the effect of ocrelizumab on NEDA using re-baselining analysis, and the predictive value of NEDA status. Methods NEDA was assessed in a modified intent-to-treat population ( n = 1520) from the pooled OPERA I and OPERA II studies over various epochs in patients with relapsing MS receiving ocrelizumab (600 mg) or interferon beta-1a (IFN β‐1a; 44 μg). Results NEDA was increased with ocrelizumab vs IFN β-1a over 96 weeks by 75% ( p < 0.001), from Week 0‒24 by 33% ( p < 0.001) and from Week 24‒96 by 72% ( p < 0.001). Among patients with disease activity during Weeks 0‒24, 66.4% vs 24.3% achieved NEDA during Weeks 24‒96 in the ocrelizumab and IFN β-1a groups (relative increase: 177%; p < 0.001). Conclusion Superior efficacy with ocrelizumab compared with IFN β-1a was consistently seen in maintaining NEDA status in all epochs evaluated. By contrast with IFN β-1a, the majority of patients with disease activity early in the study subsequently attained NEDA status with ocrelizumab.

The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis

2016 ◽  
Vol 23 (1) ◽  
pp. 94-105 ◽  
Author(s):  
Diego Cadavid ◽  
Jeffrey A Cohen ◽  
Mark S Freedman ◽  
Myla D Goldman ◽  
Hans-Peter Hartung ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Composite Endpoint ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Dominant Hand ◽  
Expanded Disability Status Scale ◽  
Disability Progression ◽  
Minimum Threshold ◽  
Secondary Progressive ◽  
Disability Status

Background: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function. Objective: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment. Methods: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm ( n = 215) data, we analyzed disability progression using a novel progression endpoint, “EDSS-Plus,” defined as progression on ⩾1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ⩾24 weeks apart and with a ⩾20% minimum threshold change for T25FW and 9HPT. Results: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors’ times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone. Conclusion: The 24-week confirmed minimum worsening of ⩾20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression.

scholarly journals Determinants of therapeutic lag in multiple sclerosis

2021 ◽  
pp. 135245852098130
Author(s):  
Izanne Roos ◽  
Emmanuelle Leray ◽  
Federico Frascoli ◽  
Romain Casey ◽  
J William L Brown ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Expanded Disability Status Scale ◽  
Disability Progression ◽  
Delayed Onset ◽  
Disease Characteristics ◽  
Disability Status ◽  
Male Sex ◽  
Pre Treatment ◽  
Patient Subgroups

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2–34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3–36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5–65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2–61.5). Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

scholarly journals Should We Use Clinical Tools to Identify Disease Progression?

2021 ◽  
Vol 11 ◽  
Author(s):  
Hernan Inojosa ◽  
Undine Proschmann ◽  
Katja Akgün ◽  
Tjalf Ziemssen
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Markers ◽  
Disability Progression ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Secondary Progressive ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Clinical Tools

The presence of disability progression in multiple sclerosis (MS) is an important hallmark for MS patients in the course of their disease. The transition from relapsing remitting (RRMS) to secondary progressive forms of the disease (SPMS) represents a significant change in their quality of life and perception of the disease. It could also be a therapeutic key for opportunities, where approaches different from those in the initial phases of the disease can be adopted. The characterization of structural biomarkers (e.g., magnetic resonance imaging or neurofilament light chain) has been proposed to differentiate between both phenotypes. However, there is no definite threshold between them. Whether the risk of clinical progression can be predicted by structural markers at early disease phases is still a focus of clinical research. However, several theories and pathological evidence suggest that both disease phenotypes are part of a continuum with common pathophysiological mechanisms. In this case, the clinical evaluation of the patients would play a preponderant role above destruction biomarkers for the early identification of disability progression and SPMS. For this purpose, the use of clinical tools beyond the Expanded Disability Status Scale (EDSS) should be considered. Besides established functional tests such as the Multiple Sclerosis Functional Composite (MSFC), patient's neurological history or digital resources may help neurologists in the decision-taking. In this article, we discuss arguments for the use of clinical markers in the detection of secondary progressive MS and the characterization of progressive disease activity.

scholarly journals Coping strategies and mood profiles in patients with multiple sclerosis

2014 ◽  
Vol 72 (7) ◽  
pp. 490-495 ◽  
Author(s):  
Aysel Milanlioglu ◽  
Pinar Güzel Özdemir ◽  
Vedat Cilingir ◽  
Tezay Çakin Gülec ◽  
Mehmet Nuri Aydin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Coping Strategies ◽  
Healthy Subjects ◽  
Activity Levels ◽  
Expanded Disability Status Scale ◽  
Secondary Progressive ◽  
Rehabilitation Programs ◽  
Mcdonald Criteria ◽  
Progressive Type ◽  
Disability Status

Objective: The aim of the present study was to investigate the coping strategies, mood characteristics and the association between these aspects in patients diagnosed with multiple sclerosis and healthy subjects. Method: Fifty consecutive patients who were diagnosed with multiple sclerosis according to McDonald criteria and thirty-one healthy subjects were included in the study. In addition to the sociodemographic form, Expanded Disability Status Scale (EDSS), Coping Orientation for Problem Experiences Scale (COPE), and Profile of Mood States (POMS) tests were applied to the participants. Results: Non-functional coping strategies were significantly higher in the secondary-progressive type (p≤0.05). Depression-dejection, fatigue-inertia and total POMS scores were significantly higher in the secondary-progressive type (p≤0.05). Conclusion: The results of our study demonstrate the importance of rehabilitation programs that encourage exercise among patients with multiple sclerosis to increase vigor-activity levels.

scholarly journals Infratentorial and spinal cord lesions: Cumulative predictors of long-term disability?

2019 ◽  
Vol 26 (11) ◽  
pp. 1381-1391 ◽  
Author(s):  
Iris Dekker ◽  
Madeleine H Sombekke ◽  
Lisanne J Balk ◽  
Bastiaan Moraal ◽  
Jeroen JG Geurts ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Odds Ratio ◽  
Expanded Disability Status Scale ◽  
Simultaneous Presence ◽  
Disability Progression ◽  
Spinal Cord Lesions ◽  
Disability Status ◽  
Lesion Analysis

Objective: The objective of the study was to determine whether early infratentorial and/or spinal cord lesions are long-term cumulative predictors of disability progression in multiple sclerosis (MS). Methods: We selected 153 MS patients from the longitudinal Amsterdam MS cohort. Lesion analysis was performed at baseline and year 2. Disability progression after 6 and 11 years was measured using the Expanded Disability Status Scale (EDSS) and EDSS-plus (including 25-foot walk and 9-hole peg test). Patients with spinal cord or infratentorial lesions were compared for the risk of 6- and 11-year disability progression to patients without spinal cord or infratentorial lesions, respectively. Subsequently, patients with lesions on both locations were compared to patients with only spinal cord or only infratentorial lesions. Results: Baseline spinal cord lesions show a higher risk of 6-year EDSS progression (odds ratio (OR): 3.6, p = 0.007) and EDSS-plus progression (OR: 2.5, p = 0.028) and 11-year EDSS progression (OR: 2.8, p = 0.047). Patients with both infratentorial and spinal cord lesions did not have a higher risk of 6-year disability progression than patients with only infratentorial or only spinal cord lesions. Conclusion: The presence of early spinal cord lesions seems to be a dominant risk factor of disability progression. Simultaneous presence of early infratentorial and spinal cord lesions did not undisputedly predict disability progression.

scholarly journals Polymorphisms in the CIITA −168A/G (rs3087456) and CIITA +1614G/C (rs4774) may influence severity in multiple sclerosis patients

2019 ◽  
Vol 77 (3) ◽  
pp. 166-173 ◽  
Author(s):  
Valéria Coelho Santa Rita Pereira ◽  
Fabrícia Lima Fontes-Dantas ◽  
Eduardo Ribeiro Paradela ◽  
Fabíola Rachid Malfetano ◽  
Simone de Souza Batista Scherpenhuijzen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Course ◽  
Nucleotide Polymorphisms ◽  
Expanded Disability Status Scale ◽  
Disability Progression ◽  
Single Nucleotide ◽  
Disability Status ◽  
Multiple Sclerosis Patients ◽  
The Impact ◽  
Lower Odds Ratio

ABSTRACT It is currently unknown how genetic factors may influence the clinical course of multiple sclerosis (MS). Objective: We examined the impact of CIITA polymorphisms −168A/G (rs3087456) and +1614G/C (rs4774) on the risk of disability progression, severity and on responses to first-line immunomodulator treatments. Methods: Genomic DNA was extracted from blood samples. We used ABI3730xl and GeneMapper v.4.0 software to identify genotype variations. All patients were followed up and clinically reassessed at three-month intervals. Disability progression was measured by the Expanded Disability Status Scale and disease severity by the Multiple Sclerosis Spasticity Scale (MSSS). Results: We included 37 men and 80 women. We found no evidence regarding the influence of the single nucleotide polymorphisms studied in the Expanded Disability Status Scale or therapeutic response of the evaluated drugs. We performed a logistic regression analysis with the MSSS and found that a less severe MS course was associated with wild type CIITA −168AA and CIITA +1614GG, as the chance of the patient progressing to MSSS2 and MSSS3 decreased in 61% and 75% with CIITA −168AA and 66% and 75% with CIITA +1614GG, respectively (p < 0.0001). Although less significant, the CIITA +1614 GC also pointed to a less severe MS course and the chance of the patient progressing to MSSS3 decreased 79% (p = 0.015). We also observed that the CIITA −168GG genotype was more frequent in MSSS2 and MSSS3 and had 40% lower odds ratio to becoming more severe MS. Conclusion: These data suggest that CIITA −168AA, CIITA +1614GG and CIITA +1614 GC polymorphisms may be associated with a better MS clinical course. This knowledge may be useful for a better understanding of MS and its therapeutic management.

Clinical follow-up of 304 patients with multiple sclerosis three years after mitoxantrone treatment

2007 ◽  
Vol 13 (5) ◽  
pp. 626-631 ◽  
Author(s):  
M. Debouverie ◽  
L. Taillandier ◽  
S. Pittion-Vouyovitch ◽  
S. Louis ◽  
H. Vespignani
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Progressive Multiple Sclerosis ◽  
Expanded Disability Status Scale ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Before And After ◽  
The Mean ◽  
Disease Modifying Treatment

The objectives of this study were to assess the benefits of 1) mitoxantrone after three years of follow-up and 2) disease-modifying treatment (DMT) after stopping mitoxantrone. A retrospective analysis was performed on 304 patients with active relapsing-remitting (RR) or progressive multiple sclerosis (PMS) who were treated with mitoxantrone. After mitoxantrone therapy, some patients received DMT (interferon-beta or glatiramer acetate) while others did not. The disease course of the two groups was evaluated by the Expanded Disability Status Scale (EDSS) before and after mitoxantrone and then every year for three years. The mean EDSS score at starting mitoxantrone and three years after stopping mitoxantrone respectively, were: 3.3 (1.3) and 3.2 (1.7) for the RRMS patients and 5.9 (1.2) and 6.4 (1.4) for the PMS patients. Before starting mitoxantrone, demographic and clinical parameters of predictive disability were not significantly different between patients who received DMT or not. The variation of EDSS between time of stopping mitoxantrone and three years later was significantly different (+0.9 versus +0.3; P=0.03) for patients with RRMS. We found that mitoxantrone treatment induces stable disease up to two years after discontinuation of mitoxantrone therapy. In the third year, patients without DMT deteriorated. Multiple Sclerosis 2007; 13: 626-631. http://msj.sagepub.com

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