Expanded Disability Status Scale Change Research Articles

Paramagnetic rim lesions predict greater long-term relapse rates and clinical progression over 10 years

Background: Paramagnetic rim lesions (PRLs) have been linked to higher clinical disease severity and relapse frequency. However, it remains unclear whether PRLs predict future, long-term disease progression. Objectives: The study aimed to assess whether baseline PRLs were associated with subsequent long-term (10 years) Expanded Disability Status Scale (EDSS) increase and relapse frequency and, if so, whether PRL-associated EDSS increase was mediated by relapse. Methods: This retrospective analysis included 172 people with multiple sclerosis (pwMS) with 1868 yearly clinical visits over a mean follow-up time of 10.2 years. 3T magnetic resonance imaging (MRI) was acquired at baseline and PRLs were assessed on quantitative susceptibility mapping (QSM) images. The associations between PRLs, relapse, and rate of EDSS change were assessed using linear models. Results: PRL+ pwMS had greater overall annual relapse rate (β = 0.068; p = 0.010), three times greater overall odds of relapse (exp(β) = 3.472; p = 0.009), and greater rate of yearly EDSS change (β = 0.045; p = 0.010) than PRL− pwMS. Greater PRL number was associated with greater odds of at least one progression independent of relapse activity (PIRA) episode over follow-up (exp(β) = 1.171, p = 0.009). Mediation analysis showed that the association between PRL presence (yes/no) and EDSS increase was 96.7% independent of relapse number. Conclusion: PRLs are a marker of aggressive ongoing disease inflammatory activity, including more frequent future clinical relapses and greater long-term, relapse-independent disability progression.

Late-onset multiple sclerosis: disability trajectories in relapsing-remitting patients of the Italian MS Registry.

Generally infrequent, multiple sclerosis (MS) with late onset (LOMS) is characterized by an onset over the age of 50 and a mainly progressive course, while relapsing-remitting (RR) forms are less frequently observed and explored. This study aimed to characterize a large cohort of MS patients with RRMS at onset to assess the baseline factors related to the worst disability trajectories and explore the role of LOMS. The data were extracted from the Italian MS Register (IMSR). Disability trajectories, defined using at least two and up to twenty expanded disability status scale (EDSS) assessments annually performed, were implemented using group-based trajectory models (GBTMs) to identify different groups with the same trajectories over time. MS profiles were explored using multinomial logistic regression. A total of 16,159 RR patients [1012 (6.26%) presented with LOMS] were analyzed. The GBTM identified four disability trajectories. The group with the most severe EDSS trend included 12.3% of the patients with a mean EDSS score > 4, which increased over time and exceeded 6 score. The group with medium severity EDSS trend comprised 21.9% of the patients and showed a change in EDSS > 3 scores over time. The largest group with 50.8% of patients reported a constant EDSS of 2 score. Finally, the benign group comprised 14.9% of the patients with a low and constant EDSS of 1 score over time. The probability of being in the worst groups increased if the patient was male; had LOMS or experienced brainstem, spinal, or supratentorial symptoms. Four MS severity profiles among RRMS patients in the IMSR have been reported, with LOMS being associated with a rapid worsening of EDSS scores. These findings have important implications for recognizing and managing how older age, aging, and age-related factors interact with MS and its evolution.

Sex differences in multiple sclerosis relapse presentation and outcome: a retrospective, monocentric study of 134 relapse events.

Reporting of sex-specific analyses in multiple sclerosis (MS) is sparse. Disability accrual results from relapses (relapse-associated worsening) and independent thereof (progression independent of relapses). A population of MS patients during relapse treated per standard of care was analyzed for sex differences and short-term relapse outcome (3-6 months) as measured by Expanded Disability Status Scale (EDSS) change. Single-center retrospective study. We analyzed 134 MS relapses between March 2016 and August 2020. All events required relapse treatment (steroids and/or plasma exchange). Demographic, disease, and paraclinical characteristics [cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI)] were displayed separated by sex. Multivariable linear regression was run to identify factors associated with short-term EDSS change. Mean age at relapse was 38.4 years (95% confidence interval: 36.3-40.4) with a proportion of 71.6% women in our cohort. Smoking was more than twice as prevalent in men (65.8%) than women (32.3%). In- and after-relapse EDSSs were higher in men [men: 3.3 (2.8-3.9), women: 2.7 (2.4-3.0); men: 3.0 (1.3-3.6); women: 1.8 (1.5-2.1)] despite similar relapse intervention. Paraclinical parameters revealed no sex differences. Our primary model identified female sex, younger age, and higher EDSS at relapse to be associated with EDSS improvement. A higher immunoglobulin G (IgG) quotient (CSF/serum) was associated with poorer short-term outcome [mean days between first relapse treatment and last EDSS assessment 130.2 (79.3-181.0)]. Sex and gender differences are important in outcome analyses of MS relapses. Effective treatment regimens need to respect putative markers for a worse outcome to modify long-term prognosis such as clinical and demographic variables, complemented by intrathecal IgG synthesis. Prospective trials should be designed to address these differences and confirm our results.

Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis

BackgroundWe aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS).MethodsA total of 141...

Bariatric surgery outcomes in multiple sclerosis: Interplay with vitamin D and chronic pain syndromes.

Obesity and lower vitamin D levels are associated with adverse outcomes in multiple sclerosis (MS). Bariatric surgery is a safe intervention in patients with MS, although it lowers vitamin D levels in the general population. To investigate the effects of bariatric surgery on vitamin D levels and interrogate risk factors for unsuccessful post-operative weight loss in patients with MS. We retrospectively identified patients with MS who underwent bariatric surgery from 2001 to 2023. Wilcoxon signed rank tests for paired samples were used to compare pre- and post-operative body mass index (BMI), expanded disability status scale (EDSS), timed 25-foot walk (T25FW), and median vitamin D values. Following bariatric surgery, patients with MS had a decrease in BMI (mean percent total weight loss of 18.4%, range 0-38%, p<0.001) and an increase in vitamin D values (mean increase of 23 ng/mL, range -4-32 ng/mL, p<0.001), while no change in EDSS or T25FW was seen. Four out of 20 patients did not lose more than 5% of their pre-operative BMI, all of whom had chronic pain syndromes and were on gabapentin. Healthy vitamin D levels are attainable following bariatric surgery in patients with MS.

Impact of menopause on relapse rate and disability level in patients with multiple sclerosis (MS): a systematic review and meta-analysis

BackgroundMenopause is a physiologic phase in women’s lives. Findings regarding multiple sclerosis (MS) course through menopause are diverse. So, we designed this systematic review and meta-analysis to estimate the impact of menopause on relapse rate, and disability status in women with MS.MethodsPubMed, Scopus, EMBASE, Web of Science, and google scholar were systematically searched by two independent researchers on January 1st, 2023. They also evaluated conference abstracts, and references of the included studies. In addition, data regarding the total number of participants, name of the first author of the publication, publication year, country of origin, disease duration, disease type, annual relapse rate, and Expanded Disability Status Scale (EDSS) before and after menopause were recorded.ResultsA literature search revealed 1024 records. Twenty-one full texts were evaluated, and finally, four studies were included for meta-analysis. Mean ARR before menopause ranged between 0.21 and 0.37, and after menopause ranged between 0.13 and 0.08. The SMD of mean ARR ranged between − 1.04, and − 0.29, while the pooled SMD was estimated as -0.52(95% CI: -0.88, -0.15) (I2 = 73.6%, P = 0.02). The mean EDSS before menopause ranged between 1.5 and 2, and after menopause ranged between 2 and 3.1. The SMD of EDSS ranged between 0.46, and 0.71. The pooled SMD of EDSS change (after menopause-before menopause) estimated as 0.56(95% CI: 0.38, 0.73)(I2 = 0, P = 0.4).ConclusionThe result of this systematic review and meta-analysis show that menopause can be associated with relapse rate reduction, unlike increase in disease-related disability in women with MS.

Genetic influences on disease course and severity, 30 years after a clinically isolated syndrome.

Multiple sclerosis risk has a well-established polygenic component, yet the genetic contribution to disease course and severity remains unclear and difficult to examine. Accurately measuring disease progression requires long-term study of clinical and radiological outcomes with sufficient follow-up duration to confidently confirm disability accrual and multiple sclerosis phenotypes. In this retrospective study, we explore genetic influences on long-term disease course and severity; in a unique cohort of clinically isolated syndrome patients with homogenous 30-year disease duration, deep clinical phenotyping and advanced MRI metrics. Sixty-one clinically isolated syndrome patients [41 female (67%): 20 male (33%)] underwent clinical and MRI assessment at baseline, 1-, 5-, 10-, 14-, 20- and 30-year follow-up (mean age ± standard deviation: 60.9 ± 6.5 years). After 30 years, 29 patients developed relapsing-remitting multiple sclerosis, 15 developed secondary progressive multiple sclerosis and 17 still had a clinically isolated syndrome. Twenty-seven genes were investigated for associations with clinical outcomes [including disease course and Expanded Disability Status Scale (EDSS)] and brain MRI (including white matter lesions, cortical lesions, and brain tissue volumes) at the 30-year follow-up. Genetic associations with changes in EDSS, relapses, white matter lesions and brain atrophy (third ventricular and medullary measurements) over 30 years were assessed using mixed-effects models. HLA-DRB1*1501-positive (n = 26) patients showed faster white matter lesion accrual [+1.96 lesions/year (0.64-3.29), P = 3.8 × 10-3], greater 30-year white matter lesion volumes [+11.60 ml, (5.49-18.29), P = 1.27 × 10-3] and higher annualized relapse rates [+0.06 relapses/year (0.005-0.11), P = 0.031] compared with HLA-DRB1*1501-negative patients (n = 35). PVRL2-positive patients (n = 41) had more cortical lesions (+0.83 [0.08-1.66], P = 0.042), faster EDSS worsening [+0.06 points/year (0.02-0.11), P = 0.010], greater 30-year EDSS [+1.72 (0.49-2.93), P = 0.013; multiple sclerosis cases: +2.60 (1.30-3.87), P = 2.02 × 10-3], and greater risk of secondary progressive multiple sclerosis [odds ratio (OR) = 12.25 (1.15-23.10), P = 0.031] than PVRL2-negative patients (n = 18). In contrast, IRX1-positive (n = 30) patients had preserved 30-year grey matter fraction [+0.76% (0.28-1.29), P = 8.4 × 10-3], lower risk of cortical lesions [OR = 0.22 (0.05-0.99), P = 0.049] and lower 30-year EDSS [-1.35 (-0.87,-3.44), P = 0.026; multiple sclerosis cases: -2.12 (-0.87, -3.44), P = 5.02 × 10-3] than IRX1-negative patients (n = 30). In multiple sclerosis cases, IRX1-positive patients also had slower EDSS worsening [-0.07 points/year (-0.01,-0.13), P = 0.015] and lower risk of secondary progressive multiple sclerosis [OR = 0.19 (0.04-0.92), P = 0.042]. These exploratory findings support diverse genetic influences on pathological mechanisms associated with multiple sclerosis disease course. HLA-DRB1*1501 influenced white matter inflammation and relapses, while IRX1 (protective) and PVRL2 (adverse) were associated with grey matter pathology (cortical lesions and atrophy), long-term disability worsening and the risk of developing secondary progressive multiple sclerosis.

The natural history of primary progressive multiple sclerosis: insights from the German NeuroTransData registry

BackgroundPrimary progressive multiple sclerosis (PPMS) is characterised by gradual worsening of disability from symptom onset. Knowledge about the natural course of PPMS remains limited.MethodsPPMS patients from the German NeuroTransData (NTD) MS registry with data from 56 outpatient practices were employed for retrospective cross-sectional and longitudinal analyses. The cross-sectional analysis included a contemporary PPMS cohort with a documented visit within the last 2 years before index date (1 Jan 2021). The longitudinal analysis included a disease modifying therapy (DMT)-naïve population and focused on the evolution of expanded disability status scale (EDSS) from the first available assessment at or after diagnosis within the NTD registry to index date. Outcome measures were estimated median time from first EDSS assessment to first 24-week confirmed EDSS ≥ 4 and ≥ 7. Besides EDSS change, the proportion of patients on disability pension were described over time.ResultsThe cross-sectional analysis included 481 PPMS patients (59.9% female, mean [standard deviation, SD] age 60.5 [11.5] years, mean [SD] EDSS 4.9 [2.1]). Estimated median time from first EDSS assessment after diagnosis to reach 24-week confirmed EDSS ≥ 4 for DMT-naïve patients was 6.9 years. Median time to EDSS ≥ 7 was 9.7 years for 25% of the population. Over a decade mean (SD) EDSS scores increased from 4.6 (2.1) to 5.7 (2.0); the proportion of patients on disability pension increased from 18.9% to 33.3%.ConclusionsThis study provides first insights into the German NTD real-world cohort of PPMS patients. Findings confirm the steadily deteriorating course of PPMS accompanied by increasingly limited quality of life.

The effects of different types of smoking on recovery from attack in hospitalized multiple sclerosis patients

BackgroundSeveral studies demonstrated the association between tobacco smoking and higher risk and increased progression of multiple sclerosis (MS). Data about the effect of smoking during the recovery from MS attacks is limited. Furthermore, different types of tobacco exposures such as water pipe and passive smoking are not well assessed separately. So this study evaluated the effect of different types of smokes, cigarette and water pipe as well as passive smoking on the function recovery of relapsing-remitting MS (RRMS) attacks MethodsThis cohort study evaluated the adult patients with RRMS and Expanded Disability Status Scale (EDSS) < 5 in the attack phase. Patients were divided into two groups: smokers and non-smokers. The smokers included those who use cigarette, water pipe as well as passive smokers as subgroups for more analyses later. EDSS was monitored after relapse and two months after relapse. Change of EDSS considered as the criteria for functional recovery. The correlation between the amount of consumption and disability level was assessed among smokers by Pearson’s correlation test. While, the difference of EDSS between smoker and non-smoker were assessed by Independent samples T-test. Results142 patients were evaluated. 79 (55.6%) were smokers (43% male) while 63 (44.4%) were non-smokers (36.5% male). There was a statistically significant difference in change of EDSS between smoker and non-smoker groups, which change of EDSS was higher in non-smoker (−2.62 ± 0.90 non-smoker vs. −1.75 ± 0.76 smoker, P < 0.001). Also, only there was a significantly lesser decline in EDSS after two months in the cigarette smokers in subgroups analyses (P < 0.001). A correlation analysis revealed a significant positive correlation between the number per day of cigarette smoking and EDSS after relapse (r = 0.3, P = 0.03) and a significant positive correlation between minutes per month of smoking of water pipe and EDSS two months after relapse (r = ‎0.6‎‎, P > 0.001). ConclusionTobacco smoking especially cigarette smoking is associated with a negative effect on recovery from the attack in patients with RRMS.

Comparison of multiple sclerosis patients with or without rebound activity after fingolimod cessation: Five-year clinical outcomes.

Patients with multiple sclerosis (MS) who discontinue fingolimod might present with rebound activity. The reasons for the development of rebound have been identified, but there are limited data on the long-term clinical outcomes of these patients. This study aimed to compare the long-term outcomes of patients with MS with and without rebound activity after fingolimod discontinuation. A total of 31 patients who discontinued fingolimod for various reasons with a minimum follow-up of 5 years were included in the study. Of these, 10 were assigned to the rebound group and 21 to the non-rebound group. Clinical and demographic data and 5-year clinical outcomes of both groups were prospectively examined. At fingolimod initiation, there were no significant differences in age, disease duration, and Expanded Disability Status Scale (EDSS) score. The annualized relapse rate (ARR) was significantly higher in the rebound group than in the non-rebound group before the fingolimod treatment (p = 0.005). In the rebound group, EDSS scores 2 months after rebound treatment and at the 5-year follow-up were not significantly different than before fingolimod initiation (p = 0.14 and p = 0.46, respectively). The last recorded EDSS was significantly higher in the non-rebound group than in the rebound group (3.6 ± 2.3 vs. 2.15 ± 1.4, p = 0.045). At the last follow-up, one patient was diagnosed with secondary progressive multiple sclerosis in the rebound group (10%), and 11 patients were in the non-rebound group (52.4%, p = 0.05). When rebound activity is well-monitored and treated after fingolimod discontinuation, no overall EDSS change is expected in the long-term follow-up.

Glial fibrillary acidic protein and multiple sclerosis progression independent of acute inflammation.

The clinical relevance of serum glial fibrillary acidic protein (sGFAP) concentration as a biomarker of MS disability progression independent of acute inflammation has yet to be quantified. To test whether baseline values and longitudinal changes in sGFAP concentration are associated with disability progression without detectable relapse of magnetic resonance imaging (MRI) inflammatory activity in participants with secondary-progressive multiple sclerosis (SPMS). We retrospectively analyzed longitudinal sGFAP concentration and clinical outcome data from the Phase 3 ASCEND trial of participants with SPMS, with no detectable relapse or MRI signs of inflammatory activity at baseline nor during the study (n = 264). Serum neurofilament (sNfL), sGFAP, T2 lesion volume, Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and composite confirmed disability progression (CDP) were measured. Linear and logistic regressions and generalized estimating equations were used in the prognostic and dynamic analyses. We found a significant cross-sectional association between baseline sGFAP and sNfL concentrations and T2 lesion volume. No or weak correlations between sGFAP concentration and changes in EDSS, T25FW, and 9HPT, or CDP were observed. Without inflammatory activity, changes in sGFAP concentration in participants with SPMS were neither associated with current nor predictive of future disability progression.

Siponimod Stabilizes Physical Disability Scores in People Living With Secondary Progressive Multiple Sclerosis After 2 Years of Treatment: Analysis From the Novartis Global Managed Access Program (P8-3.010)

<h3>Objective:</h3> To describe demographic and clinical characteristics and characterize change in Expanded Disability Status Scale (EDSS) score in people living with secondary progressive multiple sclerosis (plwSPMS) receiving siponimod under the managed access program (MAP; Global Siponimod MAP cohort [BAF2001M cohort]). <h3>Background:</h3> Siponimod significantly reduced the risk of confirmed disability progression and worsening of cognitive processing speed vs placebo in the phase 3 EXPAND trial (NCT01665144). However, real-world effectiveness data for siponimod remain scarce. <h3>Design/Methods:</h3> The BAF2001M cohort is an umbrella program to facilitate access to siponimod when marketing authorization is pending (under physician request) in the absence of acceptable alternative treatments. The program started in March 2019 and is ongoing. The target population included adult patients with SPMS and an EDSS score &lt;7 from March 2019 to January 2021. After January 2021, access to the MAP required SPMS with active disease. Treatment selection and patient monitoring were based on physician assessment. Baseline characteristics included country, age, sex, relapse, MRI activity in the last 2 years, EDSS, and cognition evaluation. <h3>Results:</h3> A total of 632 cases were analyzed (153 excluded from analysis due to local country restrictions). Mean (SD) age was 52.3 (8.7) years, 60% of patients were female, and median (IQR) EDSS was 5.5 (4.5–6.5). Prior to siponimod start, ~51% experienced a relapse in the last 2 years, 54% had previous cognitive evaluation, and 52% had an MRI scan in the last 2 years (48% showed activity). Mean change in EDSS from baseline was approximately −0.02/−0.03 at Months 6, 12, 18, and 24 (not significantly different vs baseline). Approximately 94% (140/149) of patients improved or were stable at Month 24. <h3>Conclusions:</h3> Most plwSPMS demonstrated improved or stabilized EDSS scores over 2 years. This population was older than the EXPAND study population and around half demonstrated relapse/MRI activity. Results support the effectiveness of siponimod in SPMS. <b>Disclosure:</b> Dr. Mavrikis Cox has received personal compensation for serving as an employee of Novartis Pharmaceuticals. Dr. Mavrikis Cox has stock in Novartis Pharmaceuticals. Virginia DeLasHeras has nothing to disclose. Dr. Ryan has received personal compensation for serving as an employee of Novartis. Mrs. Istrate has nothing to disclose. Soudeh Ansari has received personal compensation for serving as an employee of Novartis. Sophie Arnould has nothing to disclose. Dr. Piani Meier has received personal compensation for serving as an employee of Novartis. Dr. Piani Meier has received personal compensation for serving as an employee of Merck Group.

Correlation of disability with quality of life in patients with multiple sclerosis treated with natalizumab: primary results and post hoc analysis of the TYSabri ImPROvement study (PROTYS)

BackgroundIn patients with multiple sclerosis (MS), relapses and disability progression have been associated with decreased health-related quality of life (HRQoL).MethodsPROTYS, a prospective, multicentre, single-arm, observational study in seven Swiss MS...

Evaluation of Rosuvastatin Therapy on SIRT1 Gene Expression in Patients with Multiple Sclerosis: An Uncontrolled Clinical Trial

Multiple sclerosis (MS) is a chronic autoimmune disease. Current medications have some limitations such as low efficacy and high side effects. In recent years, statins have been raised as potential therapeutics for MS treatment with minimal complications. In addition, patient monitoring using suitable molecular markers is necessary for treatment response evaluation. The aim of the present study was the evaluation of SIRT1 gene expression changes following rosuvastatin therapy in patients with MS. This before-after uncontrolled clinical trial study was performed on 25 patients with MS. Patients were treated with 20 mg rosuvastatin daily for 3 months. The Expanded Disability Status Scale (EDSS) was measured before and after statin therapy. Blood samples were taken from patients 2 times, before and after statin therapy, and centrifuged for white blood cell isolation. Total RNA was extracted using RNX-plus reagent, and complementary DNA was synthesized using Pars Tous cDNA Synthesis Kit. Real-time polymerase chain reaction was done using SYBR blue master mix and gene-specific primers in Roche light cycler. Patients' information was recorded using a checklist. Data analysis was performed using SPSS version 23 and Graph Pad version 9 software and P < 0.05 was considered a significant level. SIRT1 was significantly upregulated in MS patients after statin therapy. Subsequently, EDSS of patients was decreased along with the increase in SIRT1 gene expression, although EDSS changes were not significant (P > 0.05). Pearson correlation test showed no significant relationship between EDSS and SIRT1 gene expression (P > 0.05). No significant relationship was observed between SIRT1 expression or EDSS levels with patients' age, sex, weight, height, and body mass index and administrated drugs (P > 0.05). SIRT1 potentially is a sensitive and reliable biomarker for patients with MS monitoring during statin therapy.

Patient-Reported-Outcomes and Safety of Autologous Stem Cell Transplantation in Multiple Sclerosis: A Single Center Experience with the "Mexican Method" in 1300 Persons

BACKGROUND Multiple sclerosis (MS) is a central nervous system autoimmune, inflammatory, demyelinating, and neurodegenerative disease that significantly lowers the quality of life for those affected. Autologous hematopoietic cell transplantation (aHSCT) has been demonstrated to be superior to new immunomodulatory drugs and is currently a proven therapeutic strategy, the patient reported outcomes (PROs) assessing the expanded-disability status scale (EDSS) improving in around 80%. We have previously reported that autotransplants for several hematologic malignancies can be done in the outpatient setting using refrigerated non frozen peripheral blood stem cells. We now report data from persons with MS receiving autotransplants in an outpatient setting using refrigerated blood cells followed for up to 24 months after aHSCT. MATERIALS AND METHODS Since June 2015, 1,300 consecutive patients with MS have been autografted in the Centro de Hematología y Medicina Interna de Puebla, México using non-frozen peripheral blood stem cells. All the aHSCT were started as outpatients, employing the "Mexican method": Cyclophosphamide 200 mg/kg and rituximab 1,000 mg; protocol is registered in ClinicalTrials.gov identifier NCT02674217. Eligibility criteria included all the following: Karnofsky performance score >70%, EDSS ≤8 in the 2 weeks pretransplant, CNS magnetic resonance image (MRI) ≤3 mo pretransplant, normal heart, liver, lung, and kidney function, ≥6 mo since exposure to immune suppressive drugs. The primary outcome measure was the PRO (EDSS changes) and secondary outcomes were overall survival (OS) and progression-free survival (PFS). Disability progression was defined as patients with EDSS ≤5.5 who experienced a PRO-EDSS increase of ≥1.0, whereas for patients with EDSS >5.5, progression was a PRO-EDSS increase of ≥0.5. RESULTS A total of 1300 persons were prospectively included (871 females and 429 males); median age was 47 years. 637 patients presented with relapsing remitting MS (RRMS), 390 with secondary progressive (SPMS) and 273 with primary progressive (PPMS). All procedures were started on an outpatient basis; 45 persons (3.5%) needed to be admitted to the hospital during the procedure as a result of neutropenic fever (20), pneumothorax (4), nausea and/or vomiting (4) or other complications; there were two fatalities (0.1%). One to three apheresis (median 1) were needed to obtain at least 1x106/Kg viable CD34 cells. Patients recovered above 0.5 x109/L absolute granulocytes on day 8 (median, range 2-13), whereas platelet recovery above 20 x109/L on day 4 (median, range 0-10). Patients remained in our premises for 28 days and PROs were surveyed by phone / zoom every 3 months after aHSCT. PROs could be recorded in 382/1300 persons (29%): PRO-response rate (no disability progression) at 12 months was 80% for all the patients,( 81.4% for RRMS, 76.2% for PPMS and 80% for SPMS). At 24 months the response rate was 85.8% for RRMS, 77.3% for PPMS and. 70% for SPMS. Changes in the EDSS score were statistically better at 12 (p<0.0001), 18 (p=0.0017) and 24 months (p=0.0003). CONCLUSIONS aHSCT for persons with MS employing the "Mexican method" is very safe and related with a positive PRO response rate (around 80% for all patients) at 12 and 24 months; results are better than those informed employing immunosuppressive drugs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Rebaseline no evidence of disease activity (NEDA-3) as a predictor of long-term disease course in a Norwegian multiple sclerosis population.

No evidence of disease activity with three components (NEDA-3) is achieved if the person with MS (pwMS) has no new MRI lesions, no new relapses and no change in Expanded disability status scale (EDSS) over 1 year. Whether NEDA-3 is a good tool in measuring disease activity is up for discussion, but it is superior to the individual parameters separately and user-friendly. There is disagreement on whether NEDA-3 is a good predictor of long-term disability. This is a retrospective cohort study using real-world data with limited selection bias from the complete MS population at two hospitals in the southeast of Norway. We included pwMS diagnosed between 2006 and 2017 who had enough information to determine time to failure of NEDA-3 after diagnosis. Of 536 pwMS, only 38% achieved NEDA 1 year after diagnosis. PwMS achieving NEDA were more likely to be started on a high efficacy drug as the initial drug, but there were no demographic differences. Mean time to NEDA failure was 3.3 (95% CI 2.9-3.7) years. Starting a high efficiacy therapy was associated with an increased risk of sustaining NEDA as compared to those receiving moderate efficacy therapy. PwMS who achieved NEDA at year one had a mean time to EDSS 6 of 33.8 (95% CI 30.9-36.8) years vs. 30.8 (95% CI 25.0-36.6) years in pwMS who did not achieve NEDA, p < 0.001. When rebaselining NEDA 1 year after diagnosis, 52.2% achieved NEDA in the 1st year after rebaseline, mean time to NEDA failure was 3.4 (95% CI 3.0-3.7) years and mean time to EDSS 6 was 44.5 (95% CI 40.4-48.5) years in pwMS achieving NEDA vs. 29.6 (95% CI 24.2-35.0) years in pwMS not achieving NEDA, p < 0.001. After rebaseline, pwMS with a high efficacy therapy as the initial drug had a mean time from diagnosis to NEDA fail of 4.8 years (95% CI 3.9-5.8) vs. 3.1 years (95% CI 2.7-3.5) in pwMS started on a moderate efficacy therapy, p < 0.001. In pwMS with NEDA failure at year one, 70% failed one, 28% failed two and 2% failed three components. New MRI lesions were the most common cause of NEDA failure (63%), followed by new relapses (50%) and EDSS change (25%). NEDA-3 from rebaseline after 1 year, once treatment is stabilized, can predict the long-term disease course in MS. Starting a high efficacy DMT is associated with longer time to NEDA failure than moderate therapies. Finally, most pwMS only fail one component and new MRI lesions are the most likely cause of NEDA failure.

Contemporary study of multiple sclerosis disability in South East Wales

BackgroundA contemporary understanding of disability evolution in multiple sclerosis (MS) is an essential tool for individual disease management and planning of interventional studies. We have used prospectively collected longitudinal data...

Relationship between Patient Preferences, Attitudes to Treatment, Adherence, and Quality of Life in New Users of Teriflunomide.

Background: A poor patient adherence often limits the real-world effectiveness of an oral disease-modifying therapy (DMT) for multiple sclerosis (MS). In the present study, we aimed to map patient preferences, attitudes toward treatment, and quality of life to identify the predictors of non-adherence to teriflunomide. Methods: This was a single-arm, non-interventional, multicenter study (Czech Act 378/2007 Coll.) consisting of three visits: the first at treatment initiation (teriflunomide 14 mg), and then after 3 and 9 months of therapy. We enrolled both DMT-naïve and patients who had undergone a DMT diagnosed with a clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS). The functional status and MS activity were estimated using the Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR); the quality of life via the Multiple Sclerosis Impact Scale (MSIS-29); the medication adherence with the Morisky Medication Adherence Scale (MMAS-8); the confidence in the ability to take medications by the Self-Efficacy for Appropriate Medication Score (SEAMS); and the attitude to the therapy via the Beliefs about Medicines Questionnaire (BMQ). After nine months of therapy, we predicted the adherence to teriflunomide (MMAS-8) by fitting a multivariate ordinal logistic model with EDSS changes, gender, previous DMT, MSIS-29, BMQ, and SEAMS as the explanatory variables. Results: Between 2018 and 2019, 114 patients were enrolled at 10 sites in the Czech Republic. The mean age was 41.2 years, 64.8% were diagnosed with a CIS, 52.4% were DMT-naïve, and 98.1% of patients preferred an oral administration at the baseline. The mean EDSS baseline was 1.97 and remained constant during the 9 months of therapy. The ARR baseline was 0.72 and dropped to 0.19 and 0.15 after 3 and 9 months, respectively. Despite a more than 4-fold higher ARR baseline, the treatment-naïve patients achieved an ARR at 9 months comparable with those previously treated. There were ten non-serious adverse reactions. After nine months of teriflunomide therapy, 63.3%, 21.2%, and 15.4% of patients had a high, medium, and low adherence, respectively, as per the MMAS-8; 100% of patients preferred an oral administration. The SEAMS score (odds ratio (OR) = 0.91; p = 0.013) and previous DMT (OR = 4.28; p = 0.005) were the only significant predictors of non-adherence. The disability, the quality of life, and beliefs about medicines had no measurable effect on adherence. Conclusion: After nine months of teriflunomide therapy, both the disability and quality of life remained stable; the relapse rate significantly decreased, 63.3% of patients had a high adherence, and 100% of patients preferred an oral administration. A low adherence was associated with previous DMT experiences and a low self-efficacy for the appropriate medication (i.e., the confidence in one’s ability to take medication correctly).

Spinal cord lesions and brain grey matter atrophy independently predict clinical worsening in definite multiple sclerosis: a 5-year, multicentre study

ObjectivesTo evaluate the combined contribution of brain and cervical cord damage in predicting 5-year clinical worsening in a multicentre cohort of definite multiple sclerosis (MS) patients.MethodsBaseline 3.0T brain and cervical...

Assessment of T2 lesion-based disease activity volume outcomes in predicting disease progression in multiple sclerosis over 10 years

BackgroundNew/enlarging T2 lesion count and T2-lesion volume (LV) are used as conventional secondary endpoints in clinical trials of patients with multiple sclerosis (PwMS). However, those outcomes may have several limitations, such as inability to account for heterogeneity of lesion formation/enlargement frequency and their dynamic volumetric behavior. Measurement of volume rather than count of new/enlarging lesions may be more representative outcome of dynamic changes over time. ObjectivesTo investigate whether new/enlarging T2-LV is more predictive of confirmed disability progression (CDP), compared to total T2-LV or new/enlarging T2 lesion count over long-term follow-up. MethodsWe studied 176 early relapsing-remitting PwMS who were followed with annual MRI examinations over 10 years. T2-LV, new/enlarging T2-LV, and new/enlarging lesion count were determined. Cumulative count/volumes were obtained. 10-year CDP was confirmed after 48-weeks. ANCOVA analysis detected MRI outcome differences in stable (n = 76) and CDP (n = 100) groups at different time points, after correction for multiple comparisons. ResultsPwMS with CDP had greater cumulative new/enlarging T2-LV at 4 years (p = 0.049), and enlarging T2-LV at 4- (p = 0.039) and 6-year follow-up (p = 0.032), compared to stable patients. PwMS with CDP did not differ from stable ones in new/enlarging T2 lesion count or total T2-LV at any of the study timepoints. PwMS with Expanded Disability Status Scale change >2.0 had significantly greater enlarging T2 lesion count (p = 0.01) and enlarging T2-LV (p = 0.038) over the 10-year follow-up. ConclusionEnlargement of T2 lesions is more strongly associated with long-term disability progression compared to other conventional T2 lesion-based outcomes.