Impact of natural menopause on multiple sclerosis: a multicentre study

ObjectiveTo study the effect of natural menopause on multiple sclerosis clinical course.MethodsThis was an observational, retrospective, multicentre, cohort study. Menopause onset was defined by the final menstrual period (FMP) beyond which no menses occurred for 12 months. We included multiple sclerosis (MS) patients with FMP occurred after 2005 and a recorded follow-up of at least 2 years pre-FMP and post-FMP. We excluded patients with primary progressive course, iatrogenic menopause and with other confounders that could mask menopause onset. We compared relapse-rate and expanded disability status scale (EDSS) scores pre-FMP and post-FMP, searching for possible interactions with age, disease duration, cigarette smoking and nulliparity status.Results148 patients were included (mean observation: 3.5 years pre-FMP and post-FMP). Most patients (92%) received disease-modifying therapies, mainly first-lines. After menopause the annualised relapse rate (ARR) significantly decreased (from 0.21±0.31 to 0.13± 0.24; p=0.005), while disability worsened (increase of mean 0.4 vs 0.2 points after menopause; p<0.001). Older age and long-lasting disease were associated with ARR reduction (p=0.013), but not with disability worsening. Cigarette smokers showed a trend to a higher disability accumulation after menopause (p=0.059).ConclusionNatural menopause seems to be a turning point to a more progressive phase of MS. Relapse rate is also reduced after menopause, but this effect could be driven most by ageing and shifting to progressive phase in patients with long-lasting disease. Cigarette smoking could speed up disability progression after menopause.

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Safety and Efficacy of Rituximab in Multiple Sclerosis: A Retrospective Observational Study

Journal of Immunology Research ◽

10.1155/2018/9084759 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 20

Author(s):

Bassem I. Yamout ◽

Nabil K. El-Ayoubi ◽

Johny Nicolas ◽

Yehya El Kouzi ◽

Samia J. Khoury ◽

...

Keyword(s):

Multiple Sclerosis ◽

Relapse Rate ◽

Perianal Abscess ◽

Disability Progression ◽

Surgical Interventions ◽

Disability Status ◽

Relapsing Remitting ◽

Clinical Practice Setting ◽

Magnetic Resonance Imaging Mri

Objective. To evaluate the efficacy and safety of rituximab in multiple sclerosis in a clinical practice setting. Methods. Clinical data for all adult patients with multiple sclerosis (MS) treated with off-label rituximab at a single MS center in Lebanon between March 2008 and April 2017 were retrospectively collected from medical charts. The main efficacy outcomes assessed were annualized relapse rate (ARR) and proportion of patients free from relapses, disability progression, or magnetic resonance imaging (MRI) activity. Results. A total of 89 rituximab-treated patients were included: 59 relapsing-remitting MS (RRMS) and 30 progressive MS (PMS). Patients were treated with 1000 or 2000 mg rituximab IV every 6–12 months for a mean duration of 22.2 ± 24.8 months. The subjects were 65.2% females with a mean age of 40.5 ± 12.3 years and a mean disease duration of 7.9 ± 6.2 years. During treatment, the ARR decreased from 1.07 at baseline to 0.11 in RRMS (p<0.0001) and from 0.25 to 0.16 in PMS patients (p=0.593). The mean Expanded Disability Status Scale (EDSS) remained unchanged in both RRMS and PMS patients. Between baseline and the last follow-up, the percent of patients free from any new MRI lesions increased from 18.6% to 92.6% in the RRMS group and from 43.3% to 82% in the PMS group. No evidence of disease activity (NEDA) was achieved in 74% of patients at 1 year of treatment. A total of 64 adverse events (AEs) (71.9%) were recorded with the most common being infusion-related reactions in 25.8% of patients, all mild in nature. Two of our rituximab-treated patients experienced serious AEs requiring surgical interventions: pyoderma gangrenosum vaginalis with perianal abscess and fistula and an increase in the size of a meningioma. No case of progressive multifocal leukoencephalopathy (PML) was detected. Conclusion. In our real-world cohort, rituximab was well-tolerated and effective in reducing relapse rate and disability progression in relapsing-remitting and progressive MS patients.

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Determinants of therapeutic lag in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458520981300 ◽

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.

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Disability progression in aggressive multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458516653273 ◽

2016 ◽

Vol 23 (3) ◽

pp. 456-463 ◽

Cited By ~ 7

Author(s):

Suresh Menon ◽

Feng Zhu ◽

Afsaneh Shirani ◽

Joel Oger ◽

Mark S Freedman ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Duration ◽

Patient Characteristics ◽

Expanded Disability Status Scale ◽

Disability Progression ◽

Disease Modifying Drugs ◽

Primary Progressive ◽

Disability Status ◽

The Mean

Objective: To examine disease progression in ‘aggressive’ multiple sclerosis (MS), British Columbia, Canada (1980–2009). Methods: Aggressive (or ‘malignant’) MS was defined as Expanded Disability Status Scale (EDSS) ⩾6 within 5 years from onset. The first EDSS ⩾6 was termed ‘baseline’. Within 2, 3 and 5 years post-baseline, patients were categorized as follows: ‘worsened’ or ‘improved’, relative to baseline EDSS (the remainder exhibited no change or had no new scores). The associations between patient characteristics (sex, relapsing onset/primary progressive, onset age, onset symptoms, disease duration, cumulative prior relapses and baseline EDSS) and worsening in disability were examined longitudinally using logistic regression. Results: Of the 225/4341 (5.2%) aggressive/malignant MS patients, 134 (59.6%) were female, 167 (74.2%) were relapsing onset, 94 (41.8%) had received disease-modifying drugs at some point and the mean follow-up was 8.7 years. The proportion of patients who ‘worsened’ increased from 40.4% to 57.8%, while those who ‘improved’ varied little (range, 8.9%–10.2%). The odds of worsening increased with disease duration (adjusted odds ratio (AOR) = 1.36; 95% confidence interval (CI) = 1.22–1.52) and the presence of primary progressive (vs relapsing-onset) MS (AOR = 1.85; 95% CI = 1.01–3.38). Conclusion: Apart from disease duration and a primary progressive course, no clinically useful associations of subsequent disease worsening in patients with aggressive/malignant MS were identified.

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Treatment of multiple sclerosis with rituximab: A multicentric Italian–Swiss experience

Multiple Sclerosis Journal ◽

10.1177/1352458519872889 ◽

2019 ◽

Vol 26 (12) ◽

pp. 1519-1531 ◽

Cited By ~ 5

Author(s):

Chiara Zecca ◽

Francesca Bovis ◽

Giovanni Novi ◽

Marco Capobianco ◽

Roberta Lanzillo ◽

...

Keyword(s):

Multiple Sclerosis ◽

Relapse Rate ◽

B Lymphocyte ◽

Outcome Analysis ◽

Off Label ◽

Disability Status ◽

Relapsing Remitting ◽

First Relapse ◽

Anti Cd20

Background: Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS). Objective: To investigate the effectiveness and safety of rituximab in relapsing–remitting (RR) and progressive MS. Methods: This is a multicenter, retrospective study on consecutive MS patients treated off-label with rituximab in 22 Italian and 1 Swiss MS centers. Relapse rate, time to first relapse, Expanded Disability Status Scale (EDSS) progression, incidence of adverse events, and radiological outcomes from 2009 to 2019 were analyzed. Results: A total of 355/451 enrolled subjects had at least one follow-up visit and were included in the outcome analysis. Annualized relapse rate significantly decreases after rituximab initiation versus the pre-rituximab start year in RRMS (from 0.86 to 0.09, p < .0001) and in secondary-progressive (SP) MS (from 0.34 to 0.06, p < .0001) and had a slight decrease in primary-progressive (PP) MS patients (from 0.12 to 0.07, p = 0.45). After 3 years from rituximab start, the proportion of patients with a confirmed EDSS progression was 14.6% in the RRMS group, 24.7% in the SPMS group, and 41.5% in the PPMS group. No major safety concerns arose. Conclusion: Consistently with other observational studies, our data show effectiveness of rituximab in reducing disease activity in patients with MS.

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Alemtuzumab treatment in Denmark: A national study based on the Danish Multiple Sclerosis Registry

Multiple Sclerosis Journal ◽

10.1177/13524585211003291 ◽

2021 ◽

pp. 135245852110032

Author(s):

Asta Theodorsdottir ◽

Birgit Debrabant ◽

Melinda Magyari ◽

Matthias Kant ◽

Peter V Rasmussen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Relapse Rate ◽

Population Based ◽

Additional Treatment ◽

National Study ◽

Annual Number ◽

Specific Patient ◽

Real World Setting ◽

Disability Status

Objective: To investigate clinical outcomes in a real-world setting in the complete population-based cohort of alemtuzumab-treated MS patients in Denmark. Methods: Data were retrieved from The Danish Multiple Sclerosis Registry between 2009 and 2019. Demographic and disease-specific patient parameters related to treatment history, efficacy, and safety outcomes were assessed at baseline and during follow-up visits. Results: A total of 209 patients (78% female) started treatment with alemtuzumab during the study period with 3.1 ± 1.4 years follow-up. After 2 years, 75% of patients were relapse-free compared to 48% the year before alemtuzumab ( p < 0.001). The annual number of relapses was reduced by 69% in year 4 compared with the year prior alemtuzumab. More active disease before alemtuzumab increased the annual hazard rate for relapse (HR: 2.88, p < 0.001). The Expanded Disability Status Scale (EDSS) score remained stable or improved in 81% of patients after 2 years. The need for an additional treatment course was associated with higher number of relapses in the year before alemtuzumab (odds ratio (OR) = 1.95, p = 0.001). Conclusion: In a country with primarily escalation strategy, relapse rate reduction was maintained for 5 years, and EDSS stabilized/improved in majority of patients. Higher relapse rate 1 year before alemtuzumab increased the odds for additional courses. Novel serious AEs were not observed.

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The Italian Multiple Sclerosis Database Network (MSDN): the risk of worsening according to IFNβ exposure in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458506070620 ◽

2006 ◽

Vol 12 (5) ◽

pp. 578-585 ◽

Cited By ~ 20

Author(s):

Maria Trojano ◽

Pierluigi Russo ◽

Aurora Fuiani ◽

Damiano Paolicelli ◽

Elisabetta Di Monte ◽

...

Keyword(s):

Multiple Sclerosis ◽

Propensity Score ◽

Relapse Rate ◽

Cox Regression ◽

Response To Treatment ◽

Disability Progression ◽

Proportion Of Days Covered ◽

Clinical Stabilization ◽

Multiple Sclerosis Patients

We evaluated the risk of worsening according to the length of exposure to interferon beta (IFNβ)ina large cohort of 2090 multiple sclerosis patients collected by the Italian MS Database Network. Overall 44-140 patient-visits with a follow-up of 22-143 patient-years were evaluated. Forty-one per cent of patients were exposed to IFNβ for up to 2 years, 39% for 2- 4 years and 20% for more than 4 years. A Cox regression model was used to analyse two clinical outcomes: disability progression and worsening of relapse rate. The technique of propensity score was applied to reduce bias in the comparison of non-randomized groups. The risks of disability progression (HR=0.23; 95% CI: 0.17 - 0.30) and worsening of relapse rate (HR=0.19; 95% CI: 0.14 - 0.27) were reduced by about 4- 5- fold in patients exposed to IFNβ for more than four years, compared with patients exposed for up to two years. The propensity score technique confirmed the findings. The proportion of days covered by IFNβ treatment was lower ( P<0.0001) in patients exposed to IFNβ for up to two years than in other groups. A clinical stabilization over two years of IFNβ exposure may predict a subsequent good clinical response to treatment.

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Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection

Journal of Clinical Medicine ◽

10.3390/jcm10010002 ◽

2020 ◽

Vol 10 (1) ◽

pp. 2

Author(s):

Rosa Escudero-Sánchez ◽

María Ruíz-Ruizgómez ◽

Jorge Fernández-Fradejas ◽

Sergio García Fernández ◽

María Olmedo Samperio ◽

...

Keyword(s):

Clinical Trials ◽

Real World ◽

Recurrence Rates ◽

Factors Associated ◽

Clostridioides Difficile ◽

Multicentre Cohort Study ◽

Clostridioides Difficile Infection ◽

Prevention Of Recurrence ◽

Multicentre Cohort

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.

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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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Walking capacities in multiple sclerosis measured by global positioning system odometer

Multiple Sclerosis Journal ◽

10.1177/1352458506070667 ◽

2007 ◽

Vol 13 (2) ◽

pp. 220-223 ◽

Cited By ~ 24

Author(s):

A Créange ◽

I Serre ◽

M Levasseur ◽

D Audry ◽

A Nineb ◽

...

Keyword(s):

Multiple Sclerosis ◽

Global Positioning System ◽

Walking Speed ◽

Walking Distance ◽

Expanded Disability Status Scale ◽

Satellite Technology ◽

Promising Tool ◽

Disability Status ◽

Global Positioning

We used a global positioning satellite technology odometer to determine the maximum objective walking distance capacity (MOWD) of patients with multiple sclerosis (MS). The MOWD correlated with Expanded Disability Status Scale (EDSS) score (r2 =0.41; P < 0.0001), the MSWS-12 scale (r2 = 0.46; P < 0.0001), time to walk 10 m (r2 = 0.51; P < 0.02) and walking speed (r2 =0.75; P < 0.001). Limitation of walking capacities was measurable up to 4550 m, strikingly above the 500-m limit of the EDSS. This objective odometer is a promising tool for evaluation and follow-up of patients with MS. Multiple Sclerosis 2007; 13: 220–223. http://msj.sagepub.com

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Prospective study of multiple sclerosis with early onset

Multiple Sclerosis Journal ◽

10.1191/1352458502ms786oa ◽

2002 ◽

Vol 8 (2) ◽

pp. 115-118 ◽

Cited By ~ 93

Author(s):

A Ghezzi ◽

C Pozzilli ◽

M Liguori ◽

M G Marrosu ◽

N Milani ◽

...

Keyword(s):

Multiple Sclerosis ◽

First Year ◽

Hormonal Changes ◽

Disability Status ◽

Definite Multiple Sclerosis ◽

Relapsing Remitting ◽

Clinically Definite Multiple Sclerosis ◽

The Mean ◽

And Gender

Fifty-four subjects (36 females and 18 males) affected by clinically definite multiple sclerosis (MS) and with onset of the disease at 15 years of age or before were prospectively studied in five Italian MS centres. Female/male ratio was 4.7 in subjects with age ≥12 years, suggesting a role of hormonal changes in triggering MS onset. The mean follow-up duration was 10.9-5.6 years. The functional systems more frequently involved at onset were the pyramidal and brainstem (both in 28% of cases). The onset was monosymptomatic in 31 subjects (57%). The course was relapsing-remitting in 39 subjects (72%) and relapsing-progressive in 15 (28%). Disability was assessed by the Expanded Disability Status Scale (EDSS): the mean score after 8 years of follow up was 3.5 (-2.5). The score was <4 in 68% of cases, between 4 and 6 in 8% of cases, > 6 in 24% of cases. Disability after 8 years was highly predicted by disability in the first year (p=0.008). There was a tendency to a worse prognosis in relation to the number of relapses in the first 2 years (p=0.08). The outcome was not influenced by the characteristics of symptoms at onset, age and gender.

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