The improved understanding of multiple sclerosis (MS) neurobiology alongside the development of novel markers of disease will allow precision medicine to be applied to MS patients, bringing the ...promise of improved care. Combinations of clinical and paraclinical data are currently used for diagnosis and prognosis. The addition of advanced magnetic resonance imaging and biofluid markers has been strongly encouraged, since classifying patients according to the underlying biology will improve monitoring and treatment strategies. For example, silent progression seems to contribute significantly more than relapses to overall disability accumulation, but currently approved treatments for MS act mainly on neuroinflammation and offer only a partial protection against neurodegeneration. Further research, involving traditional and adaptive trial designs, should strive to halt, repair or protect against central nervous system damage. To personalize new treatments, their selectivity, tolerability, ease of administration, and safety must be considered, while to personalize treatment approaches, patient preferences, risk-aversion, and lifestyle must be factored in, and patient feedback used to indicate real-world treatment efficacy. The use of biosensors and machine-learning approaches to integrate biological, anatomical, and physiological parameters will take personalized medicine a step closer toward the patient's virtual twin, in which treatments can be tried before they are applied.
Cerebral energy deficiency is increasingly recognised as an important feature of multiple sclerosis (MS). Until now, we have lacked non-invasive imaging methods to quantify energy utilisation and ...mitochondrial function in the human brain. Here, we used novel dual-calibrated functional magnetic resonance imaging (dc-fMRI) to map grey-matter (GM) deoxy-haemoglobin sensitive cerebral blood volume (CBVdHb), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen consumption (CMRO2) in patients with MS (PwMS) and age/sex matched controls. By integrating a flow-diffusion model of oxygen transport, we evaluated the effective oxygen diffusivity of the capillary network (DC) and the partial pressure of oxygen at the mitochondria (PmO2). Significant between-group differences were observed as decreased CBF (p = 0.010), CMRO2 (p < 0.001) and DC (p = 0.002), and increased PmO2 (p = 0.043) in patients compared to controls. No significant differences were observed for CBVdHb (p = 0.389), OEF (p = 0.358), or GM volume (p = 0.302). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS. Our findings may be indicative of reduced oxygen demand or utilisation in the MS brain and mitochondrial dysfunction. Our results suggest changes in brain physiology may precede MRI-detectable GM loss and may contribute to disease progression and neurodegeneration.
Background
COVID-19 vaccines have been recommended to people with multiple sclerosis (pwMS) and, to ensure durable immunity, a third booster dose has been administered in several countries. Data ...about potential risks associated with the third booster dose in pwMS, such as vaccine-triggered disease exacerbations, are still scarce.
Objective
To investigate whether the administration of a third booster dose of mRNA COVID-19 vaccines was associated with an increased risk of short-term disease reactivation in a large cohort of pwMS.
Methods
We retrospectively selected 1265 pwMS who received a third booster dose of an mRNA COVID-19 vaccine. Demographic and clinical data were collected, including the presence, number and characteristics of relapses in the 60 days prior to and after the third booster dose.
Results
In the selected cohort, the relapse rate in the two months after administration of the third booster dose of mRNA COVID-19 vaccines did not increase when compared with the prior two months. Indeed, the percentage of pwMS experiencing relapses in the 60 days following the administration of the third booster dose was 2.1%, similar to the percentage recorded in 60 days prior to vaccination, which was 1.9%.
Conclusions
The third booster dose of mRNA COVID-19 vaccines appeared to be safe for pwMS.
Objective
To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment.
Methods
This was an independent, ...multi-centre, retrospective post-marketing study. We analysed data of 1,507 patients who started teriflunomide since October 2014 and were regularly followed in 28 Centres in Italy. We reported the proportions of patients who discontinued treatment (after excluding 32 lost to follow-up) and who experienced clinical disease activity, i.e., relapse(s) and/or confirmed disability worsening, as assessed by the Expanded Disability Status Scale (EDSS). Decision tree-based analysis was performed to identify baseline factors associated with clinical disease activity during teriflunomide treatment.
Results
At database lock (September 2020), approximately 29% of patients (430 out of 1,475) discontinued teriflunomide because of disease activity (~ 46%), adverse events (~ 37%), poor tolerability (~ 15%), pregnancy planning (~ 2%). Approximately 28% of patients experienced disease activity over a median follow-up of 2.75 years: ~ 9% had relapses but not disability worsening; ~ 13% had isolated disability worsening; ~ 6% had both relapses and disability worsening. The most important baseline factor associated with disease activity (especially disability worsening) was an EDSS > 4.0 (
p
< 0.001). In patients with moderate disability level (EDSS 2.0–4.0), disease activity occurred more frequently in case of ≥ 1 pre-treatment relapses (
p
= 0.025). In patients with milder disability level (EDSS < 2.0), disease activity occurred more frequently after previous exposure to ≥ 2 disease-modifying treatments (
p
= 0.007).
Conclusions
Our study suggests a place-in-therapy for teriflunomide in naïve patients with mild disability level or in those who switched their initial treatment for poor tolerability. Adverse events related with teriflunomide were consistent with literature data, without any new safety concern.
In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying treatments (DMTs) in patients ...with relapsing–remitting multiple sclerosis. Data of patients regularly attending 21 Italian MS Centres who started a self-injectable or an oral DMT in 2015 were collected to: (1) estimate the proportion of patients discontinuing the treatment; (3) explore reasons for discontinuation; (3) identify baseline predictors of treatment discontinuation over a follow-up period of 12 months. We analyzed data of 1832 consecutive patients (1289 women, 543 men); 374 (20.4%) of them discontinued the prescribed DMT after a median time of 6 months (range 3 days to 11.5 months) due to poor tolerability (
n
= 163; 43.6%), disease activity (
n
= 95; 25.4%), adverse events (
n
= 64; 17.1%), convenience (i.e. availability of new drug formulations) and pregnancy planning (
n
= 21; 1.1%). Although the proportion of discontinuers was higher with self-injectable (
n
= 107; 22.9%) than with oral DMT (
n
= 215; 16.4%), the Cox regression model revealed no significant between-group difference (
p
= 0.12). Female sex hazard ratio (HR) = 1.39,
p
= 0.01 and previous exposure to ≥ 3 DMTs (HR = 1.71,
p
= 0.009) were two independent risk factors for treatment discontinuation, regardless of prescribed DMTs. Our study confirms that persistence to treatment represents a clinical challenge, irrespective of the route of administration.
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