Outcomes in a Modern Cohort of Treated Patients with Multiple Sclerosis from Diagnosis Up to 15 Years

Abstract Background: Before disease-modifying therapies (DMTs) were available, the natural history of multiple sclerosis (MS) regarding attainment of accepted disability milestones was reported with fairly wide variance comparing outcomes across studies. The influence of DMTs on these outcomes is unknown. This study aimed to calculate attainment of disability milestones during the first 15 years after onset of DMT-treated relapsing forms of MS (RMS). Methods: As a retrospective study, all available disability data (collected routinely) on all newly diagnosed patients with RMS seen and initially diagnosed in a single clinic between 1989 and 2006 were reviewed. Times from first symptoms and diagnosis until first treatment with DMTs were also reviewed. Time-to-event statistics were applied using disability milestones. Results: Mean follow-up of 184 adult patients from symptom onset was 13.7 years. Of patients followed up for 15 years after onset, 16 of 86 (19%) reached an Expanded Disability Status Scale (EDSS) score of 6.0. Estimated median time to reach an EDSS score of 3.0 was 10.7 years and to reach an EDSS score of 4.0 was 18.1 years. Conclusions: There were striking differences between the present results and older data sets and similar results to the few available modern data sets. This analysis of a modern treated RMS cohort provides outcomes data that may be compared favorably with the natural history of RMS.

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A Pilot Study of 24-h Motor Activity Patterns in Multiple Sclerosis: Pre-Planned Follow-Up at 2 Years

Clocks & Sleep ◽

10.3390/clockssleep3030023 ◽

2021 ◽

Vol 3 (3) ◽

pp. 366-376

Author(s):

Lorenzo Tonetti ◽

Federico Camilli ◽

Sara Giovagnoli ◽

Vincenzo Natale ◽

Alessandra Lugaresi

Keyword(s):

Multiple Sclerosis ◽

Motor Activity ◽

Activity Pattern ◽

Activity Patterns ◽

Expanded Disability Status Scale ◽

Disability Status ◽

Relapsing Remitting ◽

Edss Score ◽

Activity Prognosis

Early multiple sclerosis (MS) predictive markers of disease activity/prognosis have been proposed but are not universally accepted. Aim of this pilot prospective study is to verify whether a peculiar hyperactivity, observed at baseline (T0) in early relapsing-remitting (RR) MS patients, could represent a further prognostic marker. Here we report results collected at T0 and at a 24-month follow-up (T1). Eighteen RRMS patients (11 females, median Expanded Disability Status Scale-EDSS score 1.25, range EDSS score 0–2) were monitored at T0 (mean age 32.33 ± 7.51) and T1 (median EDSS score 1.5, range EDSS score 0–2.5). Patients were grouped into two groups: responders (R, 14 patients) and non-responders (NR, 4 patients) to treatment at T1. Each patient wore an actigraph for one week to record the 24-h motor activity pattern. At T0, NR presented significantly lower motor activity than R between around 9:00 and 13:00. At T1, NR were characterized by significantly lower motor activity than R between around 12:00 and 17:00. Overall, these data suggest that through the 24-h motor activity pattern, we can fairly segregate at T0 patients who will show a therapeutic failure, possibly related to a more active disease, at T1. These patients are characterized by a reduced morning level of motor activation. Further studies on larger populations are needed to confirm these preliminary findings.

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The Natural History of Multiple Sclerosis

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100026573 ◽

1987 ◽

Vol 14 (3) ◽

pp. 255-261 ◽

Cited By ~ 86

Author(s):

B.G. Weinshenker ◽

G.C. Ebers

Keyword(s):

Multiple Sclerosis ◽

High Risk ◽

Natural History ◽

Prospective Studies ◽

Rapid Development ◽

Clinical Markers ◽

Inception Cohort ◽

Natural History Studies ◽

History Of

ABSTRACT:Studies which have attempted to define the outcome of multiple sclerosis (MS) have methodologic difficulties arising from patient referral biases and the length of follow-up required, which make prospective studies of an inception cohort unrealistic. Means to improve the validity of retrospective natural history studies are suggested. Results of existing series are summarized and compared. Survival is only rarely shortened by MS, but disability to the point of requiring aids for ambulation occurs in 30-70% of patients by 15 years from onset of symptoms. Disagreement as to the percentage of patients who are ultimately bedridden by MS likely arises in large part due to differences in patient ascertainment and follow-up. The need to develop early clinical markers for the patient at high risk for rapid development of major disability is stressed.

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Cognitive impairment at diagnosis predicts 10-year multiple sclerosis progression

Multiple Sclerosis Journal ◽

10.1177/1352458515599075 ◽

2015 ◽

Vol 22 (5) ◽

pp. 659-667 ◽

Cited By ~ 53

Author(s):

Marcello Moccia ◽

Roberta Lanzillo ◽

Raffaele Palladino ◽

Kiara Chu-Mei Chang ◽

Teresa Costabile ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Newly Diagnosed ◽

Delayed Recall ◽

Selective Reminding ◽

Conversion Rates ◽

Disability Status ◽

Relapsing Remitting ◽

Selective Reminding Test

Background: Cognitive impairment occurs from the early phases of multiple sclerosis (MS), and more frequently affects secondary progressive (SP) subjects than relapsing–remitting (RR). Objective: To investigate relationships between cognitive dysfunctions in newly diagnosed RRMS, and long-term MS-related outcomes. Methods: The present 10-year retrospective longitudinal study included 155 RRMS subjects, tested with the Rao Brief Repeatable Battery at MS diagnosis. The reaching of Expanded Disability Status Scale (EDSS) 4.0, and the SP conversion were recorded. Results: 67 subjects (43.2%) reached EDSS 4.0, and 34 subjects (21.9%) converted to SP during a follow-up period of 10.0±1.8 years. Subjects with cognitive impairment at diagnosis had a rate of reaching EDSS 4.0 more than three times greater ( p<0.001; HR=3.183), and a rate of SP conversion more than two times greater, as compared to cognitively preserved subjects ( p=0.008; HR=2.535). In particular, better scores in the Selective Reminding Test-Delayed Recall and in the Symbol Digit Modalities Test at baseline were associated with lower SP conversion rates during the follow-up period ( p=0.018; HR=0.835; and p=0.001; HR=0.941, respectively). Conclusion: Cognitive impairment, with particular involvement of processing speed and memory, predicts disability progression and SP conversion in newly diagnosed RRMS, highlighting the importance of cognitive assessment from the beginning of MS.

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Clean intermittent self-catheterization in persons with multiple sclerosis: the influence of cognitive dysfunction

Multiple Sclerosis Journal ◽

10.1177/1352458508098599 ◽

2009 ◽

Vol 15 (3) ◽

pp. 379-384 ◽

Cited By ~ 34

Author(s):

L Vahter ◽

I Zopp ◽

M Kreegipuu ◽

P Kool ◽

T Talvik ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Decline ◽

Cognitive Dysfunction ◽

Cognitive Status ◽

Cognitive Test ◽

Disability Status ◽

Bladder Management ◽

Edss Score ◽

Time Required

Background Bladder problems are very common in persons with multiple sclerosis (PwMS). Objective The aim of this study was to investigate the ability of PwMS to learn clean intermittent self-catheterization (CISC). Methods The physical disability of 23 PwMS was evaluated with the Expanded Disability Status Scale (EDSS), and cognitive status was evaluated with the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). CISC was taught by the same continence advisor who was blinded to the cognitive test results. The ability to learn CISC was evaluated immediately after sessions and 3 months later. Twenty-three consecutive PwMS participated in the study. Results In all, 87% (20/23) of the PwMS successfully finished CISC training. The number of lessons needed to acquire CISC skills differed significantly depending on the EDSS (Spearman r = 0.682, P = 0.0003), but the total cognitive decline subscore did not influence the ability to learn CISC. Only 13% (3/23) of the PwMS failed to learn CISC. The ability to learn CISC depended on the number of lessons needed to acquire CISC ( r = −0.499, P = 0.0313) and the EDSS score ( r = −0.433, P = 0.0390) but not on the course of the disease ( r = 0.125, P = 0.5696) or on cognitive decline ( r = −0.311, P = 0.1480). After 3 months of follow-up, 30% (6/20) of the PwMS had ceased performing CISC. A follow-up indicated no statistically significant correlations among any of the subscores of the cognitive test battery, the EDSS score, the course of the disease, and the time required to learn CISC and effective bladder management. Conclusions Our study thus confirmed that most (87%) PwMS were able to learn CISC in spite of cognitive dysfunction and therefore to improve their quality of life.

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Natalizumab discontinuation in patients with multiple sclerosis: Profiling risk and benefits at therapeutic crossroads

Multiple Sclerosis Journal ◽

10.1177/1352458515570768 ◽

2015 ◽

Vol 21 (13) ◽

pp. 1713-1722 ◽

Cited By ~ 16

Author(s):

Luca Prosperini ◽

Pietro Annovazzi ◽

Marco Capobianco ◽

Ruggero Capra ◽

Fabio Buttari ◽

...

Keyword(s):

Multiple Sclerosis ◽

Propensity Score ◽

Progressive Multifocal Leukoencephalopathy ◽

Median Time ◽

Expanded Disability Status Scale ◽

Increased Risk ◽

Disability Status ◽

Edss Score ◽

Natalizumab Discontinuation

Objective: The objective of this paper is to estimate the risk of reaching well-established disability milestones after withdrawal of natalizumab (NTZ) due to concern about the risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis (MS). Methods: Data from 415 patients with MS followed-up for six years after starting NTZ were collected from seven tertiary MS centers. The risk of disability worsening, i.e. reaching Expanded Disability Status Scale (EDSS) scores of 4.0 or 6.0, and the likelihood of experiencing a disability reduction of one EDSS point (or more), were assessed by propensity score-adjusted analyses in patients who discontinued and in those still on treatment at the end of follow-up. Results: A total of 318 patients who received standard NTZ treatment without experiencing evidence of disability worsening in the first two years were included in the six-year follow-up analysis, with 196 (61.6%) still on treatment and 122 (38.4%) discontinuing after a median time of 3.5 years. Patients in the discontinuing group had a more than two-fold increased risk of disability worsening ( p = 0.007), and a 68% decreased likelihood of experiencing disability reduction ( p = 0.009) compared with the continuing group. Conclusion: While discussing the overall risk/benefit profile of NTZ, patients should be advised that, in case of treatment discontinuation, the risk of disability worsening is one in three, and increases to one in two if the EDSS score at NTZ start is above 3.0.

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Self-rated physical health predicts change in disability in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458508088917 ◽

2008 ◽

Vol 14 (7) ◽

pp. 999-1002 ◽

Cited By ~ 11

Author(s):

J Drulovic ◽

T Riise ◽

M Nortvedt ◽

T Pekmezovic ◽

M Manigoda

Keyword(s):

Multiple Sclerosis ◽

Physical Health ◽

Objective Measure ◽

The Self ◽

Disease Modifying Therapies ◽

Sf 36 ◽

Physical Scale ◽

Disability Status ◽

The Mean

Objective To examine whether self-rated physical health, as measured by the Physical Functioning Scale (PF) and the Role-physical Scale (RF) of the SF-36 Health Survey, could predict change in disability measured by the Expanded Disability Status Scale (EDSS) in patients with multiple sclerosis (MS) over a follow-up period of 3 years. Methods A group of 156 clinically definite MS patients (Poser criteria), who had never been treated with disease-modifying therapies, were recruited consecutively from an outpatient clinic setting at the Institute of Neurology, Belgrade. The self-rated physical health was measured by using PF and RF of the SF-36. Results At follow-up, 33 out of 156 patients (21%) had dropped out. The mean EDSS score had increased from 3.7 to 4.5. Multiple regression analyses using change in EDSS as the dependent variable and baseline scores of EDSS and RF as independent variables showed a significant effect for RF (standardized beta = –0.21). A similar but non-significant effect was found for PF. Dichotomizing change in disability according to clinically meaningful deterioration and using logistic regression, an odds ratio of 1.27 (95% confidence interval 1.01–1.62) was found for the smallest unit of change in the self-rated scale. This means that patients who rated their own physical health as poor had a higher increase in disability compared with patients with the same level of disability at baseline who rated their physical health better. Conclusions MS patients’ perception of their health comprises information predictive for disease development not included in the more objective measure of disability status.

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Modelling disease progression in relapsing–remitting onset multiple sclerosis using multilevel models applied to longitudinal data from two natural history cohorts and one treated cohort

Health Technology Assessment ◽

10.3310/hta20810 ◽

2016 ◽

Vol 20 (81) ◽

pp. 1-48 ◽

Cited By ~ 9

Author(s):

Kate Tilling ◽

Michael Lawton ◽

Neil Robertson ◽

Helen Tremlett ◽

Feng Zhu ◽

...

Keyword(s):

Multiple Sclerosis ◽

Natural History ◽

Longitudinal Data ◽

Disease Progression ◽

Multilevel Models ◽

Natural History Model ◽

Relapsing Remitting ◽

Edss Score ◽

The Uk

BackgroundThe ability to better predict disease progression represents a major unmet need in multiple sclerosis (MS), and would help to inform therapeutic and management choices.ObjectivesTo develop multilevel models using longitudinal data on disease progression in patients with relapsing–remitting MS (RRMS) or secondary-progressive MS (SPMS); and to use these models to estimate the association of disease-modifying therapy (DMT) with progression.DesignSecondary analysis of three MS cohorts.SettingTwo natural history cohorts: University of Wales Multiple Sclerosis (UoWMS) cohort, UK, and British Columbia Multiple Sclerosis (BCMS) cohort, Canada. One observational DMT-treated cohort: UK MS risk-sharing scheme (RSS).ParticipantsThe UoWMS database has > 2000 MS patients and the BCMS database (as of 2009) has > 5900 MS patients. All participants who had definite MS (RRMS/SPMS), who reached the criteria set out by the Association of British Neurologists (ABN) for eligibility for DMT [i.e. age ≥ 18 years, Expanded Disability Status Scale (EDSS) score of ≤ 6.5, occurrence of two or more relapses in the previous 2 years] and who had at least two repeated outcome measures were included: 404 patients for the UoWMS cohort and 978 patients for the BCMS cohort. Through the UK MS RSS scheme, 5583 DMT-treated patients were recruited, with the analysis sample being the 4137 who had RRMS and were eligible and treated at baseline, with at least one valid EDSS score post baseline.Main outcome measuresEDSS score observations post ABN eligibility.MethodsWe used multilevel models in the development cohort (UoWMS) to develop a model for EDSS score with time since ABN eligibility, allowing for covariates and appropriate transformation of outcome and/or time. These methods were then applied to the BCMS cohort to obtain a ‘natural history’ model for changes in the EDSS score with time. We then used this natural history model to predict the trajectories of EDSS score in treated patients in the UK MS RSS database. Differences between the progression predicted by the natural history model and the progression observed at 6 years’ follow-up for the UK MS RSS cohort were used as indicators of the effectiveness of the DMTs. Previously developed utility scores were assigned to each EDSS score, and differences in utility also examined.ResultsThe model best fitting the UoWMS data showed a non-linear increase in EDSS score over time since ABN eligibility. This model fitted the BCMS cohort data well, with similar coefficients, and the BCMS model predicted EDSS score in UoWMS data with little evidence of bias. Using the natural history model predicts EDSS score in a treated cohort (UK MS RSS) higher than that observed [by 0.59 points (95% confidence interval 0.54 to 0.64 points)] at 6 years post treatment.LimitationsOnly two natural history cohorts were compared, limiting generalisability. The comparison of a treated cohort with untreated cohorts is observational, thus limiting conclusions about causality.ConclusionsEDSS score progression in two natural history cohorts of MS patients showed a similar pattern. Progression in the natural history cohorts was slightly faster than EDSS score progression in the DMT-treated cohort, up to 6 years post treatment.Future workLong-term follow-up of randomised controlled trials is needed to replicate these findings and examine duration of any treatment effect.Funding detailsThe National Institute for Health Research Health Technology Assessment programme.

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