Data suggest that patients with pediatric-onset multiple sclerosis (POMS) should initiate treatment with a disease-modifying therapy early to slow progression. The PARADIG
MS
trial demonstrated that ...oral fingolimod reduced the annual rate of relapse by 82% compared with intramuscular interferon beta-1a in children with POMS. The PARADIG
MS
study had a follow-up of 2 years, but no data are available about the safety and efficacy of fingolimod for longer periods in children with POMS. Here we present two cases of children with POMS who achieved sustained clinical benefit from treatment with fingolimod for more than 2 years. The first patient, an 11-year-old male, who participate in the PARADIG
MS
study, was treatment naïve at the time of fingolimod initiation. His clinical condition remained stable over 5 years of treatment, with no relapses and no radiological lesion progression. The second patient was a female who initiated fingolimod at the age of 12 years, 2 years after her POMS diagnosis and after an 8-month trial of interferon beta-1a. The patient had experienced two relapses during interferon beta-1a but had no relapses in more than 2 years of treatment with fingolimod, and her MRI scans showed no new or active lesions. These data show that prolonged treatment with fingolimod can be safe and effective during long-term treatment as first- or second-line therapy in children with POMS.
Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, with symptoms that greatly affect quality of life (QoL). One of the most prevalent symptoms of MS is ...fatigue, also one of the main factors reducing QoL. Low levels of vitamin D (VD) are associated with worse QoL and with increased risk of developing more severe forms of the disease. Methods: In this cross-sectional study, we compared perceptions of quality of life and fatigue in 324 patients, subdivided into four groups, according to their treatment: high-dose VD therapy only, disease-modifying therapy (DMT) only, both treatments, and no treatments. All subjects completed the MSQOL-54 and the FSS questionnaires via an online survey. Results: High-dose VD treatment was associated with an increased perception of physical QoL (83.60 vs. 66.92, p < 0.001), mental QoL (75.52 vs. 59.80, p < 0.001), and fatigue (1.89 vs. 2.98, p < 0.001), compared to the DMT-only group. Treatment with DMT was associated with a worse perception of physical QoL compared to no treatment (70.58 vs. 76.53, p = 0.024). Conclusions: high-dose VD treatment is well-tolerated and associated with an increased perception of QoL in people with MS.
Patient-reported outcomes (PROs) are essential for understanding the effects of MS and its treatments on patients’ lives; they play an important role in multiple sclerosis (MS) research and practice. ...We present the protocol for an observational study to prospectively assess the effect of cladribine tablets on PROs and their correlation to disability and physical activity in adults with highly active relapsing MS switching from a first disease modifying drug (DMD) to cladribine tablets in routine clinical practice at study sites in Italy. The primary objective will be to evaluate changes from baseline in the impact of highly active MS on self-assessed physical functioning 52 weeks after the switch to cladribine tablets using the Multiple Sclerosis Impact Scale-29 (MSIS-29). Secondary objectives will include self-assessed psychological impact of highly active MS in daily life and general health after the switch to cladribine tablets as well as changes in cognitive function, anxiety, and depression symptoms. Additional PRO measures will include the Hospital Anxiety and Depression Scale (HADS), the EuroQoL 5-Dimension 5-Level (EQ-5D-5L), the Work Productivity and Activity Impairment Questionnaire: Multiple Sclerosis (WPAI:MS), and the Patient-Reported Outcomes Measurement Information System (PROMIS). Wearable devices will acquire activity data (step counts, walking speed, time asleep, and energy expenditure). Additional clinical, radiological, and laboratory data will be collected when available during routine management. The findings will complement data from controlled trials by providing insight from daily clinical practice into the effect of cladribine tablets on the patient’s experience and self-assessed impact of treatment on daily life.
Background:
The aim of the study was to evaluate the achievement of ‘no evidence of disease activity’ (NEDA) over a 12-month period in a large multicenter population with relapsing remitting multiple ...sclerosis (RRMS) treated with delayed-release dimethyl fumarate (DMF) and teriflunomide (TRF) using a propensity-score adjustment.
Methods:
A time-to-event method was used to determine the percentages of patients with RRMS (pwRRMS) in both groups achieving NEDA 3 (no relapses, no 12-week confirmed disability progression, and no new T2/gadolinium-enhancing brain lesions). We described the safety profile of the investigated drugs.
Results:
Of the 587 pwRRMS treated with DMF and the 316 pwRRMS treated with TRF, 468 pwRRMS were successfully paired by propensity score: 234 on DMF and 234 on TRF. The percentages of pwRRMS who achieved NEDA 3 were 80.3% in the DMF group and 77.2% in the TRF group. Serious adverse events occurred in four (1.9%) pwRRMS on DMF and in three (1.3%) pwRRMS on TRF.
Conclusions:
DMF and TRF significantly impacted RRMS disease activity in our study. Serious safety concerns were recorded in less than 2% of the studied population.
Background Telerehabilitation (TR) offers a valuable opportunity to improve access to care and has shown results comparable to onsite rehabilitation (SR) across different conditions. The present ...study aimed to explore the efficacy of TR and SR in improving clinically meaningful outcomes in people with multiple sclerosis (pwMS). Materials and methods Subjects enrolled in the study were assigned to one of two treatment arms: a 6-week TR intervention or a 6-week onsite rehabilitation (SR) intervention. Pre-and post-intervention evaluation included assessment of global wellbeing using the Multiple Sclerosis Quality of Life-54 scale (QoL), fatigue using the Fatigue Severity Status scale (FSS), cognitive status using the Symbol Digit Modalities Test (SDMT), and balance dysfunction using the Berg Balance Scale (BBS). Group-level and single-subject improvements were considered as outcome measures, with QoL as the primary endpoint. To determine significant group changes over time for the entire pwMS cohort, a paired t -test was applied to the overall QoL score, focusing on both physical and mental composites. An independent sample t -test was used to assess differences in baseline and follow-up performance, as well as changes over time between the intervention groups (TR and SR). This same analysis was repeated for the other clinical domains (FSS, BBS, and SDMT). The minimal clinically important difference (MCID) according to treatment group (TR vs. SR) was explored using logistic regression. Additionally, a multiple linear regression model was applied to evaluate the impact of baseline clinical-demographic features on the observed post-intervention modifications. Results A total of 51 subjects completed the study (37 women, mean age 46.3 ± 9.8, median Expanded Disability Status Scale 3.5, min. 2, max. 6.5). The entire sample benefited from the rehabilitation treatment, with significant improvements observed at both the group and individual levels across all measured domains for both intervention groups (TR vs. SR). Quality of life improved significantly (p = 0.005), as did fatigue and balance (both p < 0.001), and cognition (p = 0.003). Conclusions Both SR and TR approaches effectively improved the perception of fatigue, cognitive performance, balance, and quality of life in a population of MS patients with moderate disability.
Objectives
To evaluate the concordance between Google Maps® application (GM®) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and respective Expanded Disability ...Status Scale (EDSS)) in people with multiple sclerosis (pwMS).
Materials and methods
This is a cross-sectional multicenter study. AS and EDSS were calculated using GM® and routine clinical methods; the correspondence between the two methods was assessed. A multinomial logistic model is investigated which demographic (age, sex) and clinical features (e.g., disease subtype, fatigue, depression) might have influenced discrepancies between the two methods.
Results
Two hundred forty-three pwMS were included; discrepancies in AS and in EDDS assessments between GM® and routine clinical methods were found in 81/243 (33.3%) and 74/243 (30.4%) pwMS, respectively. Progressive phenotype (odds ratio OR = 2.8; 95% confidence interval CI 1.1–7.11,
p
= 0.03), worse fatigue (OR = 1.03; 95% CI 1.01–1.06,
p
= 0.01), and more severe depression (OR = 1.1; 95% CI 1.04–1.17,
p
= 0.002) were associated with discrepancies between GM® and routine clinical scoring.
Conclusion
GM® could easily be used in a real-life clinical setting to calculate the AS and the related EDSS scores. GM® should be considered for validation in further clinical studies.
Adapted exercise is an effective non-pharmacological tool to improve functional, cognitive, and psychological parameters in multiple sclerosis (MS), in association with increased quality of life ...(QoL) and decreased disease severity. Adipose tissue, through the production of different adipokines, is involved in regulating energy metabolism and inflammation. Adiponectin, increased in MS, circulates as oligomers of low (LMW), medium (MMW), and high molecular weight (HMW), the latter mediating the main biological effects. The aim of study was to evaluate the effects of 4 months training at moderate intensity 65% heart rate reserve (HRR) on BMI, adiponectin, and QoL in a volunteer with secondary progressive MS. The parameters were evaluated before (T0), after 4 months training (T1), and 6 months after the end of training (T2); total serum adiponectin and its oligomeric profile were evaluated. We found a reduction in BMI (-0.9%) and FAT (-2.6%), an improvement in perceived QoL and a reduced expression of total adiponectin and HMW oligomers together with decreased MS disability level at T1 measured by EDSS. Despite the limitations of a case study, this represent a starting point to understand the influence of exercise in MS and the relationship with adiponectin expression.
(1)
: Neuromuscular electrical stimulation (NMES) has beneficial effects on physical functions in Multiple sclerosis (MS) patients. However, the neurophysiological mechanisms underlying these ...functional improvements are still unclear. This study aims at comparing acute responses in spinal excitability, as measured by soleus Hoffmann reflex (H-reflex), between MS patients and healthy individuals, under three experimental conditions involving the ankle planta flexor muscles: (1) passive NMES (pNMES); (2) NMES superimposed onto isometric voluntary contraction (NMES+); and (3) isometric voluntary contraction (ISO). (2)
: In total, 20 MS patients (MS) and 20 healthy individuals as the control group (CG) took part in a single experimental session. Under each condition, participants performed 15 repetitions of 6 s at 20% of maximal voluntary isometric contraction, with 6 s of recovery between repetitions. Before and after each condition, H-reflex amplitudes were recorded. (3)
: In MS, H-reflex amplitude did not change under any experimental condition (ISO:
= 0.506; pNMES:
= 0.068; NMES+:
= 0.126). In CG, H-reflex amplitude significantly increased under NMES+ (
= 0.01), decreased under pNMES (
< 0.000) and was unaltered under ISO (
= 0.829). (4)
: The different H-reflex responses between MS and CG might reflect a reduced ability of MS patients in modulating spinal excitability.
Trends of disease activity during pregnancy, the postpartum period, and until 24 months from the delivery in the era of new drugs for the treatment of relapsing-remitting multiple sclerosis (RRMS) ...need to be investigated.
In this cross-sectional Italian multicenter study, women with RRMS were included; the disease-modifying treatment (DMT) at the time of conception included were: interferons, glatiramer acetate, teriflunomide, dimethyl fumarate, fingolimod, and natalizumab. The main outcome of the study was to determine the rate of relapse occurrence during pregnancy and the postpartum period in all women grouped for each DMT. The secondary outcome was to determine the overall disease activity assessed by NEDA 3 (relapse, disability level, and radiological activity) at 24 months from the date of delivery.
Completed data were available for 81 pregnancies (in 74 women). Women on interferons and glatiramer had longer disease duration than women on dimethyl fumarate, fingolimod, and natalizumab (
< 0.05). Overall, we recorded 25 relapses during pregnancy (11 in 11 women) and the postpartum period (14 in 14 women). Natalizumab was the most commonly DMT in women (3) who experienced relapses during pregnancy. IFNs were the most commonly prescribed DMT in women (8) who experienced relapses during the postpartum period. At logistic regression analysis, specific treatment
was not associated with relapse occurrence. No differences among the DMTs groups were recorded about NEDA 3 status at 24 months of follow-up.
In our population, there was no difference in terms of relapses occurrence, disability status, and the overall disease activity during a follow up of 24 months.
Patients with multiple sclerosis on long-term injectable therapies may suffer from the so-called “needle fatigue”, i.e., a waning commitment to continue with the prescribed injectable treatment. ...Therefore, alternative treatment strategies to enhance patients’ adherence are warranted. In this independent, multicentre post-marketing study, we sought to directly compare switching to either teriflunomide (TFN), dimethyl fumarate (DMF), or pegylated interferon (PEG) on treatment persistence and time to first relapse over a 12-month follow-up. We analyzed a total of 621 patients who were free of relapses and gadolinium-enhancing lesions in the year prior to switching to DMF (
n
= 265), TFN (
n
= 160), or PEG (
n
= 196). Time to discontinuation and time to first relapse were explored in the whole population by Cox regression models adjusted for baseline variables and after a 1:1:1 ratio propensity score (PS)-based matching procedure. Treatment discontinuation was more frequent after switching to PEG (28.6%) than DMF (14.7%; hazard ratio HR = 0.25,
p
< 0.001) and TFN (16.9%; HR = 0.27,
p
< 0.001). We found similar results even in the re-sampled cohort of 222 patients (74 per group) derived by the PS-based matching procedure. The highest discontinuation rate observed in PEG recipient was mainly due to poor tolerability (
p
= 0.005) and pregnancy planning (
p
= 0.04). The low number of patients who relapsed over the 12-month follow-up (25 out of 621, approximately 4%) prevented any analysis on the short-term risk of relapse. This real-world study suggests that oral drugs are a better switching option than low-frequency interferon for promoting the short-term treatment persistence in stable patients who do not tolerate injectable drugs.
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