Treatment modifiers across different regimens of natalizumab treatment in MS: An Italian real-world experience.

Despite its widespread use in clinical practice, the effectiveness of natalizumab extended interval dosing (EID) adopted from treatment start across different treatment intervals and individual modifiers (body mass index - BMI) is still under-investigated. Here, seven-hundred and forty-five multiple sclerosis (MS) patients, exposed to natalizumab for 3.30 ​± ​1.

Intravenous or subcutaneous natalizumab in patients with relapsing-remitting multiple sclerosis: investigation on efficiency and savings-the EASIER study.

Introduction: EASIER is a multicenter, observational, cross-sectional study investigating the consumption of healthcare resources, including healthcare professional (HCP) active working time, the costs associated with the current natalizumab intravenous (IV) administration, and the potential impact of the adoption of subcutaneous (SC) route.

Methods: The EASIER study has three parts: (1) time and motion study to measure healthcare resources and working time needed for natalizumab IV administration using a digital data collection tool operated directly by HCPs; (2) HCP structured questionnaire-based estimation of the potential impact of natalizumab SC vs. IV administration; and (3) patient survey on the burden of natalizumab administration.

Effectiveness of teriflunomide on No Evidence of Disease Activity and cognition in relapsing remitting multiple sclerosis: results of the NEDA3PLUS study.

Background: Cognitive impairment (CI) is a prevalent and debilitating manifestation of multiple sclerosis (MS); however, it is not included in the widely used concept of No Evidence of Disease Activity (NEDA-3). We expanded the NEDA-3 concept to NEDA-3 + by encompassing CI assessed through the Symbol Digit Modality Test (SDMT) and evaluated the effect of teriflunomide on NEDA3 + in patients treated in a real-world setting. The value of NEDA-3 + in predicting disability progression was also assessed.

Antibody response elicited by the SARS-CoV-2 vaccine booster in patients with multiple sclerosis: Who gains from it?

Background And Purpose: Although two doses of COVID-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease-modifying therapies (DMTs) showed less efficient responses.

Methods: This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS.

Results: Four hundred seventy-three pwMS were analyzed.

Real-World Effectiveness of Cladribine for Patients with Multiple Sclerosis: A Sicilian Multicentric Experience (Rewind Study).

Background: Cladribine tablets are a highly effective option for the treatment of relapsingremitting multiple sclerosis (RRMS).

Objective: The study aims to evaluate the effectiveness of cladribine in a real-world setting.

Methods: This prospective real-world study consecutively screened all RRMS patients from seven different MS centers in Sicily (Italy) who completed the 2-year treatment course of cladribine tablets in the period between 11 March 2019 and 31 October 2021.

Impact of treatment with dimethyl fumarate on sleep quality in patients with relapsing-remitting multiple sclerosis: A multicentre Italian wearable tracker study.

Background: Sleep disorders are common in patients with multiple sclerosis and have a bidirectional interplay with fatigue and depression.

Objective: To evaluate the effect of treatment with oral dimethyl fumarate on the quality of sleep in relapsing-remitting multiple sclerosis.

Methods: This was a multicentre observational study with 223 relapsing-remitting multiple sclerosis subjects starting treatment with dimethyl fumarate (=177) or beta interferon (=46).

Unmet needs and gaps in the identification of secondary progression in multiple sclerosis: a Southern Italy healthcare professionals' perspective.

Objective: Multiple sclerosis (MS) is a chronic disease with different clinical courses and a tendency to worsening. The relapsing-remitting MS presents acute onset and relapses of neurological symptoms, followed by their remission. This form can convert to secondary progressive MS (SPMS) with irreversible neurological worsening and disability.

Long-term follow-up (up to 11 years) of an Italian pediatric MS cohort treated with Natalizumab: a multicenter, observational study.

Background: Natalizumab (NAT) has a strong impact on disease activity of aggressive pediatric multiple sclerosis (MS), with no difference in safety profile compared to adult MS. However, available data are limited by short follow-up. Our aim was to report long-term follow-up data (up to 11 years) of a large Italian pediatric MS cohort treated with NAT.

Radiomics Analysis of Brain [F]FDG PET/CT to Predict Alzheimer's Disease in Patients with Amyloid PET Positivity: A Preliminary Report on the Application of SPM Cortical Segmentation, Pyradiomics and Machine-Learning Analysis.

Background: Early in-vivo diagnosis of Alzheimer's disease (AD) is crucial for accurate management of patients, in particular, to select subjects with mild cognitive impairment (MCI) that may evolve into AD, and to define other types of MCI non-AD patients. The application of artificial intelligence to functional brain [F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography(CT) aiming to increase diagnostic accuracy in the diagnosis of AD is still undetermined. In this field, we propose a radiomics analysis on advanced imaging segmentation method Statistical Parametric Mapping (SPM)-based completed with a Machine-Learning (ML) application to predict the diagnosis of AD, also by comparing the results with following Amyloid-PET and final clinical diagnosis.

Subcutaneous Uptake on [18F]Florbetaben PET/CT: a Case Report of Possible Amyloid-Beta Immune-Reactivity After COVID-19 Vaccination.

Introduction: Large-scale worldwide COVID-19 vaccination programs are being rapidly deployed, and high-risk patients with comorbidity are now receiving the first doses of the vaccine. Physicians should be, therefore, aware of new pitfalls associated with the current pandemic vaccination program, also in the case of [F]Florbetaben PET/CT.Case PresentationWe described the first image of [F]Florbetaben PET/CT in the evaluation of a 70-year-old male with suspicious Alzheimer disease and unclear history of heart disease.

PML risk is the main factor driving the choice of discontinuing natalizumab in a large multiple sclerosis population: results from an Italian multicenter retrospective study.

Background: Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy due to safety or efficacy issues. The aim of our study was to evaluate the NTZ discontinuation rate and reasons of discontinuation in a large Italian population of RRMS patients.

Multicenter Interventional Phase IV Study for the Assessment of the Effects on Patient's Satisfaction of Peg IFN Beta-1a (Pre-filled Pen) in Subjects With Relapsing-Remitting Multiple Sclerosis Unsatisfied With Other Injectable Subcutaneous Interferons (PLATINUM Study).

Subcutaneous (SC) interferons beta (IFN-beta) are effective therapies for the treatment of relapsing-remitting multiple sclerosis (RRMS). Factors such as dosing schedule, needle intolerance/fatigue, and side effects may impact patient satisfaction with treatment. Improvement of patient satisfaction may increase the adherence to treatment and the patient quality of life.

A randomized study of natalizumab dosing regimens for relapsing-remitting multiple sclerosis.

Background: REFINE was an exploratory, dose- and frequency-blinded, prospective, randomized, dose-ranging study in relapsing-remitting multiple sclerosis (RRMS) patients.

Objective: To examine the efficacy, safety, and tolerability of natalizumab administered via various regimens in RRMS patients.

Methods: Clinically stable RRMS patients previously treated with 300 mg natalizumab intravenously for ⩾12 months were randomized to one of six natalizumab regimens over 60 weeks: 300 mg administered intravenously or subcutaneously every 4 weeks (Q4W), 300 mg intravenously or subcutaneously every 12 weeks (Q12W), or 150 mg intravenously or subcutaneously Q12W.

Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study.

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.

Clinical effectiveness of different natalizumab interval dosing schedules in a large Italian population of patients with multiple sclerosis.

Introduction: Natalizumab (NTZ) is one of the most effective treatment options for multiple sclerosis (MS) treatment. Our study aimed to evaluate the effectiveness of NTZ when administered according to the extended dosing strategy compared with standard 4-weekly administration in a large Italian MS population.

Materials And Methods: This retrospective multicentre study included patients with relapsing-remitting MS (RR-MS) who received NTZ administrations between the 1 June 2012 and the 15 May 2018 and were followed by the 'Italian MS Register'.

Dimethyl fumarate vs Teriflunomide: an Italian time-to-event data analysis.

Background: The introduction of oral disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) changed algorithms of RRMS treatment.

Objectives: To compare the effectiveness of treatment with dimethyl fumarate (DMF) and teriflunomide (TRF) in a large multicentre Italian cohort of RRMS patients.

Materials And Methods: Patients with RRMS who received treatment with DMF and TRF between January 1st, 2012 and December 31st, 2018 from twelve MS centers were identified.

Pregnancy and the Postpartum Period in Women With Relapsing-Remitting Multiple Sclerosis Treated With Old and New Disease-Modifying Treatments: A Real-World Multicenter Experience.

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.

Incidence of multiple sclerosis in the province of Catania. A geo-epidemiological study.

Background: An increasing incidence of MS in the city of Catania was reported during 1975-2004, with a higher incidence along the south-eastern flank of the Mt.Etna. We evaluated the incidence of MS in the entire province of Catania during 2005-2015 and the spatial distribution of MS-cases using a cluster analysis.

Randomized trial of daily high-dose vitamin D in patients with RRMS receiving subcutaneous interferon β-1a.

Objective: In the phase II, randomized, double-blind, placebo-controlled Supplementation of Vigantol Oil versus Placebo Add-on in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Receiving Rebif Treatment (SOLAR) study (NCT01285401), we assessed the efficacy and safety of add-on vitamin D in patients with RRMS.

Methods: Eligible patients with RRMS treated with SC interferon-β-1a (IFN-β-1a) 44 μg 3 times weekly and serum 25(OH)D levels <150 nmol/L were included. From February 15, 2011, to May 11, 2015, 229 patients were included and randomized 1:1 to receive SC IFN-β-1a plus placebo (n = 116) or SC IFN-β-1a plus oral high-dose vitamin D 14,007 IU/d (n = 113).

Conversion to Secondary Progressive Multiple Sclerosis: Patient Awareness and Needs. Results From an Online Survey in Italy and Germany.

Few studies have investigated the experiences of patients around the conversion to secondary progressive multiple sclerosis (SPMS). ManTra is a mixed-method, co-production research project conducted in Italy and Germany to develop an intervention for newly-diagnosed SPMS patients. In previous project actions, we identified the needs and experiences of patients converting to SPMS via literature review and qualitative research which involved key stakeholders.

Pharmacokinetics and pharmacodynamics of natalizumab in pediatric patients with RRMS.

Objective: This phase I study investigated pharmacokinetic (PK) and pharmacodynamic (PD) profiles of natalizumab in pediatric patients with relapsing-remitting MS (RRMS).

Methods: Pediatric patients with RRMS who were prescribed natalizumab 300 mg IV every 4 weeks were enrolled. Blood samples were collected on days 1, 2, 8, 15, and 22 and at weeks 4, 8, 12, and 16 to estimate PK parameters; PD properties were evaluated by measuring α4-integrin saturation and lymphocyte counts over time.

Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer's disease.

Background: Aβ peptide abnormal production is associated with the development and maintenance of neuroinflammation and oxidative stress in brains from Alzheimer disease (AD) patients. Suppression of neuroinflammation may then represent a suitable therapeutic target in AD. We evaluated the efficacy of IFNβ1a in attenuating cognitive impairment and inflammation in an animal model of AD.

18F-Florbetaben PET/CT to Assess Alzheimer's Disease: A new Analysis Method for Regional Amyloid Quantification.

Background And Purpose: While AD can be definitively confirmed by postmortem histopathologic examination, in vivo imaging may improve the clinician's ability to identify AD at the earliest stage. The aim of the study was to test the performance of amyloid PET using new processing imaging algorithm for more precise diagnosis of AD.

Methods: Amyloid PET results using a new processing imaging algorithm (MRI-Less and AAL Atlas) were correlated with clinical, cognitive status, CSF analysis, and other imaging.

No evidence of disease activity (NEDA-3) and disability improvement after alemtuzumab treatment for multiple sclerosis: a 36-month real-world study.

In this retrospective, multicenter, real-world study we collected clinical and magnetic resonance imaging (MRI) data of all patients (n = 40) with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab according to a "free-of-charge" protocol available before the drug marketing approval in Italy. Almost all (39/40) started alemtuzumab after discontinuing multiple disease-modifying treatments (DMTs) because of either lack of response or safety concerns. We considered the proportion of alemtuzumab-treated patients who had no evidence of disease activity (NEDA-3) and disability improvement over a 36-month follow-up period.

Comparable efficacy and safety of dimethyl fumarate and teriflunomide treatment in Relapsing-Remitting Multiple Sclerosis: an Italian real-word multicenter experience.

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.