Relapse recovery in multiple sclerosis: Effect of treatment and contribution to long-term disability

Background Although recovery from relapses in MS appears to contribute to disability, it has largely been ignored as a treatment endpoint and disability predictor. Objective To identify demographic and clinical predictors of relapse recovery in the first 3 years and examine its contribution to 10-year disability and MRI outcomes. Methods Relapse recovery was retrospectively assessed in 360 patients with MS using the return of the Expanded Disability Status Scale (EDSS), Functional System Scale and neurologic signs to baseline at least 6 months after onset. Univariate and multivariable models were used to associate recovery with demographic and clinical factors and predict 10-year outcomes. Results Recovery from relapses in the first 3 years was better in patients who were younger, on disease-modifying treatment, with a longer disease duration and without bowel or bladder symptoms. For every incomplete recovery, 10-year EDSS increased by 0.6 and 10-year timed 25-foot walk increased by 0.5 s. These outcomes were also higher with older age and higher baseline BMI. Ten-year MRI brain atrophy was associated only with older age, and MRI lesion volume was only associated with smoking. Conclusions Early initiation of disease-modifying treatment in MS was associated with improved relapse recovery, which in turn prevented long-term disability.

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Markers for type II collagen breakdown predict the effect of disease-modifying treatment on long-term radiographic progression in patients with rheumatoid arthritis

Arthritis & Rheumatism ◽

10.1002/art.20222 ◽

2004 ◽

Vol 50 (5) ◽

pp. 1390-1399 ◽

Cited By ~ 63

Author(s):

Robert Landewé ◽

Piet Geusens ◽

Maarten Boers ◽

Désirée van der Heijde ◽

Willem Lems ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Radiographic Progression ◽

Type Ii Collagen ◽

Type Ii ◽

Disease Modifying ◽

Disease Modifying Treatment

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Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458520926955 ◽

2020 ◽

pp. 135245852092695

Author(s):

Minh Le ◽

Charles Malpas ◽

Sifat Sharmin ◽

Dana Horáková ◽

Eva Havrdova ◽

...

Keyword(s):

Multiple Sclerosis ◽

Prognostic Markers ◽

Functional System ◽

Study Cohort ◽

Disability Progression ◽

Mixed Effect ◽

Mixed Effect Models ◽

Disability Status ◽

Lower Hazard

Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear. Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms. Methods: This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores. Results: The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37, p < 0.001) and EDSS (β = 0.16, p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89, p = 0.01) and EDSS (β = −0.06, p < 0.001). Neither presentation was associated with changes in relapse risk. Conclusion: Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.

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Factors associated with time from first-symptoms to diagnosis and treatment initiation of Multiple Sclerosis in Switzerland

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318814562 ◽

2018 ◽

Vol 4 (4) ◽

pp. 205521731881456 ◽

Cited By ~ 1

Author(s):

Marco Kaufmann ◽

Jens Kuhle ◽

Milo A Puhan ◽

Christian P Kamm ◽

Andrew Chan ◽

...

Keyword(s):

Multiple Sclerosis ◽

Treatment Initiation ◽

Age At Onset ◽

Older Age ◽

Primary Progressive Multiple Sclerosis ◽

Extended Time ◽

Factors Associated ◽

Time To Diagnosis ◽

Disease Modifying ◽

Disease Modifying Treatment

Background Recent studies emphasise the importance of timely diagnosis and early initiation of disease-modifying treatment in the long-term prognosis of multiple sclerosis. Objectives The objective of this study was to investigate factors associated with extended time to diagnosis and time to disease-modifying treatment initiation in the Swiss Multiple Sclerosis Registry. Methods We used retrospective data (diagnoses 1996–2017) of the survey-based Swiss Multiple Sclerosis Registry and fitted logistic regression models (extended time to diagnosis ≥2 years from first symptoms, extended time to disease-modifying treatment initiation ≥1 year from diagnosis) with demographic and a priori defined variables. Results Our study, based on 996 persons with multiple sclerosis, suggests that 40% had an extended time to diagnosis, and extended time to disease-modifying treatment initiation was seen in 23%. Factors associated with extended time to diagnosis were primary progressive multiple sclerosis (odds ratio (OR) 5.09 (3.12–8.49)), diagnosis setting outside of hospital (neurologist (private practice) OR 1.54 (1.16–2.05)) and more uncommon first symptoms (per additional symptom OR 1.17 (1.06–1.30)). Older age at onset (per additional 5 years OR 0.84 (0.78–0.90)) and gait problems (OR 0.65 (0.47–0.89)) or paresthesia (OR 0.72 (0.54–0.95)) as first symptoms were associated with shorter time to diagnosis. Extended time to disease-modifying treatment initiation was associated with older age at diagnosis (per additional 5 years OR 1.18 (1.09–1.29)). In more recent years, time to diagnosis and time to disease-modifying treatment initiation tended to be shorter. Conclusions Even in recent periods, substantial and partially systematic variation regarding time to diagnosis and time to disease-modifying treatment initiation remains. With the emerging paradigm of early treatment, the residual variation should be monitored carefully.

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Assessment of Definitions of Sustained Disease Progression in Relapsing-Remitting Multiple Sclerosis

Multiple Sclerosis International ◽

10.1155/2013/189624 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Brian C. Healy ◽

David Engler ◽

Bonnie Glanz ◽

Alexander Musallam ◽

Tanuja Chitnis

Keyword(s):

Disease Progression ◽

Brain Mri ◽

Poor Performance ◽

Functional System ◽

Short Term ◽

Disability Status ◽

Relapsing Remitting ◽

Relapsing Remitting Multiple Sclerosis ◽

The Impact

Sustained progression on the expanded disability status scale (EDSS) is a common outcome measure of disease progression in clinical studies of MS. Unfortunately, this outcome may not accurately measure long-term and irreversible disease progression. To assess the performance of definitions of sustained progression, patients with relapsing-remitting MS (RRMS) or a clinically isolated syndrome with evidence of lesions on a brain MRI were included in our study. Fifteen definitions of sustained progression using both the EDSS and the functional system (FS) scales were investigated. The impact of both relapses and changes in provider on the probability of maintaining progression was also evaluated. Although the provider scoring the EDSS sometimes changed during followup, the provider had access to previous EDSS scores. Between 15.8% and 42.2% of patients experienced sustained progression based on the definitions using EDSS as the outcome, but nearly 50% of these patients failed to maintain sustained progression for the duration of followup. When FS scales were used, progression was most common on the pyramidal and sensory scales. Unfortunately, progression on specific FS scales failed to be more sensitive to irreversible disability. Relapses or changes in provider did not explain the poor performance of the measures. Short-term changes in the EDSS or FS scores may not be an accurate marker of irreversible change in RRMS.

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The long-term cost of multiple sclerosis in France and potential changes with disease-modifying interventions

Multiple Sclerosis Journal ◽

10.1177/1352458509102771 ◽

2009 ◽

Vol 15 (6) ◽

pp. 741-751 ◽

Cited By ~ 32

Author(s):

G Kobelt ◽

B Texier-Richard ◽

P Lindgren

Keyword(s):

Multiple Sclerosis ◽

Normal Population ◽

Productivity Losses ◽

Life Years ◽

Disability Status ◽

Disease Modifying ◽

The Cost ◽

Different Sources

Objective To evaluate the long-term costs and quality of life (QoL) with and without disease-modifying treatments (DMTs) of patients with multiple sclerosis (MS). Methods Data on resource consumption, productivity losses, QoL (utility), and fatigue were collected from 1355 patients registered with a patient association and descriptive analyses was performed. A Markov model was developed to estimate costs and utility over 20 years using the survey data. Disease progression without DMTs was taken from an epidemiological cohort in France (EDMUS cohort, LYON). Progression under DMTs was estimated from the Stockholm MS registry. Results are presented as cost per quality-adjusted life-years (QALYs), from the societal perspective, in EUR2007, discounted at 3%. Results Mean Expanded Disability Status Scale (EDSS) was 4.4 and mean total annual costs per patient were EUR44,400, of which 47% were productivity losses and 11% informal care. Public payers cover an estimated 48% of costs. Mean utility was 0.52, and the loss compared with the normal population was estimated at 0.28. Costs and utility ranged from EUR16,000 and 0.79 at EDSS 1 to EUR76,000 and 0.11 at EDSS 8–9. Over 20 years, costs were estimated at EUR429,000 and QALYs at 8.96 for patients without DMTs and at EUR433,207 and 9.24 QALYs if all patients were starting treated with DMTs at EDSS 1–3. Conclusion Although the data for this analysis come from different sources, the results indicate that the cost increase with DMTs is moderate.

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Design and Validation of an Expanded Disability Status Scale Model in Multiple Sclerosis

European Neurology ◽

10.1159/000519772 ◽

2021 ◽

pp. 1-10

Author(s):

Antonio Barreiro-González ◽

Maria T. Sanz ◽

Sara Carratalà-Boscà ◽

Francisco Pérez-Miralles ◽

Carmen Alcalá ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Cervical Spinal Cord ◽

Brain Lesion ◽

Scale Model ◽

Lesion Volume ◽

Expanded Disability Status Scale ◽

Software Analysis ◽

Disability Status ◽

Disease Modifying

Introduction: We aimed to develop and validate an Expanded Disability Status Scale (EDSS) model through clinical, optical coherence tomography (OCT), and magnetic resonance imaging (MRI) measures. Methods: Sixty-four multiple sclerosis (MS) patients underwent peripapillary retinal nerve fiber layer and segmented macular layers evaluation through OCT (Spectralis, Heidelberg Engineering). Brain parenchymal fraction was quantified through Freesurfer, while cervical spinal cord (SC) volume was assessed manually guided by Spinal Cord Toolbox software analysis. EDSS, neuroradiological, and OCT assessment were carried out within 3 months. OCT parameters were calculated as the average of both nonoptic neuritis (ON) eyes, and in case the patient had previous ON, the value of the fellow non-ON eye was taken. Brain lesion volume, sex, age, disease duration, and history of disease-modifying treatment (1st or 2nd line disease-modifying treatments) were tested as covariables of the EDSS score. Results: EDSS values correlated with patient’s age (r = 0.543, p = 0.001), SC volume (r = −0.301, p = 0.034), and ganglion cell layer (GCL, r = −0.354, p = 0.012). Using these correlations, an ordinal regression model to express probability of diverse EDSS scores were designed, the highest of which was the most probable (Nagelkerke R2 = 43.3%). Using EDSS cutoff point of 4.0 in a dichotomous model, compared to a cutoff of 2.0, permits the inclusion of GCL as a disability predictor, in addition to age and SC. Conclusions: MS disability measured through EDSS is an age-dependent magnitude that is partly conditioned by SC and GCL. Further studies assessing paraclinical disability predictors are needed.

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