Background:
Effective therapeutic strategies to preserve function and delay progression in multiple sclerosis (MS) require early recognition of individual disease trajectories.
Objectives:
To ...determine the profiles of disability evolution, identify their early predictors and develop a risk score of increasing disability.
Methods:
We analysed demographic, clinical and magnetic resonance imaging (MRI) data from patients with relapsing MS, Expanded Disability Status Scale (EDSS) score of 3.0–4.0 and follow-up ≥ 2 years. Attaining EDSS = 6.0 defined increasing disability; relapses and/or MRI defined disease activity.
Results:
In total, 344 out of 542 (63.5%) patients reached EDSS ≥ 6.0; of these, 220 (64.0%) showed disease activity. In patients with activity, the number of relapses before reaching EDSS 3.0–4.0 predicted increasing disability; age > 45 at baseline predicted increasing disability without activity. Combining age and number of relapses increased the risk of and shortened the time to EDSS = 6.0.
Conclusion:
Increasing disability is frequently associated with persistent activity. The high number of relapses identifies early those patients worsening in the presence of activity. Age predicts increasing disability in the absence of activity. The presence of both factors increases the risk of developing severe disability. As this study likely describes the transition to progression, our findings contribute to improving patient management and stratification in trials on progressive MS.
Introduction
The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in ...multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity. We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice.
Materials and methods
MS patients with drug-resistant spasticity were recruited from 30 Italian MS centers. All patients were eligible for THC:CBD treatment according to the approved label: ≥ 18 years of age, at least moderate spasticity (MS spasticity numerical rating scale NRS score ≥ 4) and not responding to the common antispastic drugs. Patients were evaluated at baseline (T0) and after 4 weeks of treatment (T1) with the spasticity NRS scale and were also asked about meaningful improvements in 6 key spasticity-related symptoms.
Results
Out of 1615 enrolled patients, 1432 reached the end of the first month trial period (T1). Of these, 1010 patients (70.5%) reached a ≥ 20% NRS score reduction compared with baseline (initial responders; IR). We found that 627 (43.8% of 1432) patients showed an improvement in at least one spasticity-related symptom (SRSr group), 543 (86.6%) of them belonging to the IR group and 84 (13.4%) to the spasticity NRS non-responders group.
Conclusion
Our study confirmed that the therapeutic benefit of cannabinoids may extend beyond spasticity, improving spasticity-related symptoms even in non-NRS responder patients.
Dimethyl fumarate (DMF), fingolimod (FTY) and teriflunomide (TFN) are oral disease-modifying therapies (DMTs) approved for relapsing–remitting multiple sclerosis (RRMS) whose efficacy and ...tolerability have been separately assessed in phase III trials. Conversely, little evidence exists about their head-to-head comparison. The aim of the study was to evaluate the 1-year persistence to DMF, FTY and TFN in patients with RRMS. Patients affected by RRMS who started treatment with DMF, FTY or TFN were identified. The study end-point was 12-month drug persistence as time to discontinuation and proportion of patients who discontinued medication within 1-year. A total of 307 patients were included (DMF = 114, FTY = 129, TFN = 64). The mean times to discontinuation were 144 (84), 189 (72) and 138 (120) days in the DMF, FTY and TFN cohorts (
p
= 0.036). At 12-month, the proportion of patients discontinuing medication was lower for subjects taking FTY (9.8%) compared with those starting DMF (21.9%) and TFN (23.6%) (
p
= 0.020). Compared to FTY cohort, DMF
adj
OR = 3.26 (1.38–7.70);
p
= 0.007 and TFN
adj
OR = 2.89 (1.10–7.63);
p
= 0.032 treated patients were more likely to have discontinued their drug at 1-year since initiation. In patients with RRMS, FTY was associated with a better persistence profile as compared to DMF and TFN.
Six-hundred twenty-one subjects with unilateral asymptomatic severe internal carotid artery (ICA) stenosis were prospectively evaluated with a median follow-up of 27 months (min = 6, max = 68). ...Vascular risk profile, plaque characteristic, stenosis progression, and common carotid artery intima-media thickness (IMT) were investigated in all patients. Outcome measures were occurrence of ischemic stroke ipsilateral to ICA stenosis and vascular death, while myocardial infarction, contralateral strokes, and transient ischemic attack were considered as competing events. A total of 99 subjects (15.9%) suffered from a vascular event. Among them, 39 were strokes ipsilateral to the stenosis (6.3%). Degree of stenosis, stenosis progression, and common carotid artery IMT resulted as independent predictive factors of ipsilateral stroke. Considering a stenosis of 60% to 70% as reference, a degree between 71% and 90% increased the risk by 2.45, while a degree between 91% and 99% increased the risk by 3.26. The progression of stenosis was a strong risk factor (hazard ratio = 4.32). Finally, the role of carotid IMT was confirmed as crucial additional measure, with an increased risk by 25% for each 0.1 mm IMT increase. Our data suggest that IMT, stenosis progression and severity should be considered as risk factors for cerebrovascular events in asymptomatic subjects with severe ICA stenosis.
The aim of this 12-month prospective study was to establish whether severe internal carotid artery stenosis is associated with faster progression of the cognitive impairment in patients with ...Alzheimer's disease (AD). Four hundred and eleven patients with AD underwent extracranial carotid Doppler ultrasound evaluation. Cerebrovascular reactivity to hypercapnia was measured by means of the breath-holding index (BHI) in those with severe carotid artery stenosis using transcranial Doppler ultrasonography. Cognitive status was quantified with the Mini Mental State Evaluation (MMSE). Ninety-eight patients had severe carotid artery stenosis, 41 right (group 1), and 57 left (group 2), while 313 had no significant stenosis (group 3). Group 1 and 2 patients showed an increased probability compared with group 3 patients to develop severe dementia (MMSE scores < 21) during the 12-month follow-up period: OR 2.36 (95% CI: 1.14-4.87) and OR 4.90 (95% CI: 2.65-9.04), respectively (p < 0.05, multiple logistic regression analysis). A BHI value ipsilateral to the stenosis < 0.69 predicted a worse MMSE score at 12 months irrespective of the side of the stenosis. These findings suggest that severe internal carotid artery stenosis can be considered as a marker of a faster rate of progression of the cognitive decline in AD. They also indicate that cerebral hemodynamic evaluation could be applied to identify patients at higher risk of rapid cognitive decline, who may benefit from aggressive treatment, and warrant investigation of the advantages of carotid revascularization procedures in these patients.
Abstract Purpose The aim of the study was to evaluate whether early disease activity during fingolimod treatment could predict disease progression in patients with relapsing-remitting multiple ...sclerosis (RRMS). Methods We included RRMS patients who received fingolimod for at least 12 months with a ≥ 36 months of follow-up. Early disease activity was assessed by the modified Rio score (MRS). Association between MRS at 12 months and time to disability progression over the following two years was assessed using Kaplan–Meier survival curves analysis and Cox proportional hazards model. Results At 1 year from starting treatment, 14 (58.3%), 5 (20.8%), 3 (12.5%) and 2 (8.3%) subjects had a MRS = 0, 1, 2, and 3, respectively. The risk of disability progression in the next 2 years was associated to the MRS and increased from 21.1% in patients with MRS = 0–1 to 80% in those with MRS ≥ 2 (adjusted HR = 19.67; 95% CI = 2.30–167.79; p = 0.006). Conclusions Early disease activity is suggested to be associated with the risk of disease progression in patients receiving fingolimod and MRS could be a reliable tool to identify the subjects at higher risk of unfavorable course.
To assess whether the presence of concomitant diseases at multiple sclerosis (MS) diagnosis is associated with the choice and the treatment persistence in an Italian MS cohort.
We included newly ...diagnosed patients (2010-2016) followed in 20 MS centers and collected demographic and clinical data. We evaluated baseline factors related to the presence of comorbidities and the association between comorbidities and the clinical course of MS and the time to the first treatment switch.
The study cohort included 2,076 patients. Data on comorbidities were available for 1,877/2,076 patients (90.4%). A total of 449/1,877 (23.9%) patients had at least 1 comorbidity at MS diagnosis. Age at diagnosis (odds ratio 1.05, 95% confidence interval CI 1.04-1.06;
< 0.001) was the only baseline factor independently related to the presence of comorbidities. Comorbidities were not significantly associated with the choice of the first disease-modifying treatment, but were significantly associated with higher risk to switch from the first treatment due to intolerance (hazard ratio 1.42, CI 1.07-1.87;
= 0.014). Association of comorbidities with risk of switching for intolerance was significantly heterogeneous among treatments (interferon β, glatiramer acetate, natalizumab, or fingolimod; interaction test,
= 0.04).
Comorbidities at diagnosis should be taken into account at the first treatment choice because they are associated with lower persistence on treatment.
Cerebral hemodynamics in patients with multiple sclerosis Lattanzi, Simona; Acciarri, Maria Cristina; Danni, Maura ...
Multiple sclerosis and related disorders,
September 2020, 2020-Sep, 2020-09-00, 20200901, Letnik:
44
Journal Article
•Changes in cerebral hemodynamics can occur in multiple sclerosis (MS).•Cerebral vasomotor reactivity (CVR) is reduced in MS patients than controls.•CVR is reduced stepwise in relapsing-remitting and ...secondary-progressive MS.
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Although the currently predominant view is that of an autoimmune inflammatory condition, changes in brain vasculature can occur and contribute to pathophysiology. The aim of this study was to evaluate cerebral hemodynamics in patients with MS and explore its relationship with disease status.
Patients with MS and age- and sex- matched healthy controls were recruited. All participants underwent assessment of cerebral hemodynamics through transcranial Doppler ultrasonography. Cerebral vasomotor reactivity (CVR) to hypercapnia was measured by the breath-holding index (BHI).
A total of 80 patients with MS and 80 healthy controls were recruited. BHI values obtained in healthy controls, relapsing-remitting (RR)-MS and secondary progressive (SP)-MS patients were 1.15±0.11, 0.87±0.18 and 0.51±0.20, respectively (p<0.001). Group-wise, patients showed decreased CVR in comparison to controls and BHI values were significantly lower in SP-MS than in RR-MS patients. At linear regression analysis, the disease form was significantly associated with cerebral hemodynamics being the SP phenotype an independent predictor of lower BHI values β=-0.36, 95% confidence interval (CI): -0.44 to -0.27, p<0.001; adjusted β=-0.37, 95% CI: -0.50 to -0.23, p<0.001).
Cerebrovascular hemodynamic insufficiency in MS may be secondary to the downstream effects of neuro-inflammatory cascades.
Background:
With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences.
Objectives:
To identify ...prognostic factors for early switch after first therapy choice.
Methods:
Newly diagnosed relapsing–remitting MS patients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models.
Results:
We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50; p = 0.009), natalizumab (HR = 0.13; p < 0.001), dimethyl-fumarate (HR = 0.60; p = 0.037), teriflunomide (HR = 0.21; p = 0.031) as compared to interferons. Younger age (HR = 0.96; p < 0.001), diagnosis delay (HR = 1.23; p = 0.021), higher baseline Expanded Disability Status Scale (HR = 1.17; p = 0.001), and spinal cord lesions (HR = 1.46; p = 0.001) were independently associated with higher inefficacy switch rates. We found lower switch for intolerance/safety with glatiramer acetate (HR = 0.61; p = 0.001), fingolimod (HR = 0.35; p = 0.002), and dimethyl-fumarate (HR = 0.57; p = 0.022) as compared to interferons, while it increased with natalizumab (HR = 1.43; p = 0.022). Comorbidities were associated with intolerance switch (HR = 1.28; p = 0.047).
Conclusion:
Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.
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