Long-term effectiveness of natalizumab in secondary progressive multiple sclerosis: A propensity-matched study.

Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 â€‹at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b. Confirmed Expanded Disability Status Scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. Out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 â€‹± â€‹25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 â€‹± â€‹19.8 years) were enrolled. After applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. The proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p â€‹= â€‹0.01). The proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p â€‹= â€‹0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67-5.7; p â€‹= â€‹0.006 and HR 2.04, 25%CI 1.22-3.35; p â€‹= â€‹0.01, respectively). Patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04-4.87; p â€‹= â€‹0.001). Treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months.

Early prediction of unfavorable evolution after a first clinical episode suggestive of multiple sclerosis: the EUMUS score.

BACKGROUND: Predicting disease progression in patients with the first clinical episode suggestive of multiple sclerosis (MS) is crucial for personalized therapeutic approaches. This study aimed to develop the EUMUS score for accurately estimating the risk of early evidence of disease activity and progression (EDA). METHODS: Retrospective analysis was conducted on data from 221 patients with a first clinical MS episode collected from four Italian MS centers. Various variables including socio-demographics, clinical features, cerebrospinal fluid analysis, evoked potentials, and brain MRI were considered. A prognostic multivariate regression model was identified to develop the EUMUS score. The optimal cutoff for predicting the transition from no evidence of disease activity (NEDA3) to EDA was determined. The accuracy of the prognostic model and score were tested in a separate UK MS cohort. RESULTS: After 12 months, 61.54% of patients experienced relapses and/or new MRI lesions. Younger age (OR 0.96, CI 0.93-0.99; p = 0.005), MRI infratentorial lesion(s) at baseline (OR 2.21, CI 1.27-3.87; p = 0.005), positive oligoclonal bands (OR 2.89, CI 1.47-5.69; p = 0.002), and abnormal lower limb somatosensory-evoked potentials (OR 2.77, CI 1.41-5.42; p = 0.003) were significantly associated with increased risk of EDA. The EUMUS score demonstrated good specificity (72%) and correctly classified 80% of patients with EDA in the independent UK cohort. CONCLUSIONS: The EUMUS score is a simple and useful tool for predicting MS evolution within 12 months of the first clinical episode. It has the potential to guide personalized therapeutic approaches and aid in clinical decision-making.

Multiple Sclerosis Progression and Relapse Activity in Children.

Importance: Although up to 20% of patients with multiple sclerosis (MS) experience onset before 18 years of age, it has been suggested that people with pediatric-onset MS (POMS) are protected against disability because of greater capacity for repair. Objective: To assess the incidence of and factors associated with progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in POMS compared with typical adult-onset MS (AOMS) and late-onset MS (LOMS). Design, Setting, and Participants: This cohort study on prospectively acquired data from the Italian MS Register was performed from June 1, 2000, to September 30, 2021. At the time of data extraction, longitudinal data from 73 564 patients from 120 MS centers were available in the register. Main Outcomes and Measures: The main outcomes included age-related cumulative incidence and adjusted hazard ratios (HRs) for PIRA and RAW and associated factors. Exposures: Clinical and magnetic resonance imaging features, time receiving disease-modifying therapy (DMT), and time to first DMT. Results: After applying the inclusion and exclusion criteria, the study assessed 16 130 patients with MS (median [IQR] age at onset, 28.7 [22.8-36.2 years]; 68.3% female). Compared with AOMS and LOMS, patients with POMS had less disability, exhibited more active disease, and were exposed to DMT for a longer period. A first 48-week-confirmed PIRA occurred in 7176 patients (44.5%): 558 patients with POMS (40.4%), 6258 patients with AOMS (44.3%), and 360 patients with LOMS (56.8%) (P < .001). Factors associated with PIRA were older age at onset (AOMS vs POMS HR, 1.42; 95% CI, 1.30-1.55; LOMS vs POMS HR, 2.98; 95% CI, 2.60-3.41; P < .001), longer disease duration (HR, 1.04; 95% CI, 1.04-1.05; P < .001), and shorter DMT exposure (HR, 0.69; 95% CI, 0.64-0.74; P < .001). The incidence of PIRA was 1.3% at 20 years of age, but it rapidly increased approximately 7 times between 21 and 30 years of age (9.0%) and nearly doubled for each age decade from 40 to 70 years (21.6% at 40 years, 39.0% at 50 years, 61.0% at 60 years, and 78.7% at 70 years). The cumulative incidence of RAW events followed a similar trend from 20 to 60 years (0.5% at 20 years, 3.5% at 30 years, 7.8% at 40 years, 14.4% at 50 years, and 24.1% at 60 years); no further increase was found at 70 years (27.7%). Delayed DMT initiation was associated with higher risk of PIRA (HR, 1.16; 95% CI, 1.00-1.34; P = .04) and RAW (HR, 1.75; 95% CI, 1.28-2.39; P = .001). Conclusions and Relevance: PIRA can occur at any age, and although pediatric onset is not fully protective against progression, this study's findings suggest that patients with pediatric onset are less likely to exhibit PIRA over a decade of follow-up. However, these data also reinforce the benefit for DMT initiation in patients with POMS, as treatment was associated with reduced occurrence of both PIRA and RAW regardless of age at onset.

SARS-CoV-2 vaccination and multiple sclerosis: a large multicentric study on relapse risk after the third booster dose.

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.

An Internet- and Kinect-Based Multiple Sclerosis Fitness Intervention Training With Pilates Exercises: Development and Usability Study.

BACKGROUND: Balance impairments are common in people with multiple sclerosis (MS), with reduced ability to maintain position and delayed responses to postural adjustments. Pilates is a popular alternative method for balance training that may reduce the rapid worsening of symptoms and the increased risk of secondary conditions (eg, depression) that are frequently associated with physical inactivity. OBJECTIVE: In this paper, we aimed to describe the design, development, and usability testing of MS Fitness Intervention Training (MS-FIT), a Kinect-based tool implementing Pilates exercises customized for MS. METHODS: MS-FIT has been developed using a user-centered design approach (design, prototype, user feedback, and analysis) to gain the target user's perspective. A team composed of 1 physical therapist, 2 game programmers, and 1 game designer developed the first version of MS-FIT that integrated the knowledge and experience of the team with MS literature findings related to Pilates exercises and balance interventions based on exergames. MS-FIT, developed by using the Unity 3D (Unity Technologies) game engine software with Kinect Sensor V2 for Windows, implements exercises for breathing, posture, and balance. Feedback from an Italian panel of experts in MS rehabilitation (neurologists, physiatrists, physical therapists, 1 statistician, and 1 bioengineer) and people with MS was collected to customize the tool for use in MS. The context of MS-FIT is traveling around the world to visit some of the most important cities to learn the aspects of their culture through pictures and stories. At each stay of the travel, the avatar of a Pilates teacher shows the user the exercises to be performed. Overall, 9 people with MS (n=4, 44% women; mean age 42.89, SD 11.97 years; mean disease duration 10.19, SD 9.18 years; Expanded Disability Status Scale score 3.17, SD 0.75) were involved in 3 outpatient user test sessions of 30 minutes; MS-FIT's usability was assessed through an ad hoc questionnaire (maximum value=5; higher the score, higher the usability) evaluating easiness to use, playability, enjoyment, satisfaction, and acceptance. RESULTS: A user-centered design approach was used to develop an accessible and challenging tool for balance training. All people with MS (9/9, 100%) completed the user test sessions and answered the ad hoc questionnaire. The average score on each item ranged from 3.78 (SD 0.67) to 4.33 (SD 1.00), which indicated a high usability level. The feedback and suggestions provided by 64% (9/14) of people with MS and 36% (5/14) of therapists involved in the user test were implemented to refine the first prototype to release MS-FIT 2.0. CONCLUSIONS: The participants reported that MS-FIT was a usable tool. It is a promising system for enhancing the motivation and engagement of people with MS in performing exercise with the aim of improving their physical status.

Acoustic Voice Analysis as a Useful Tool to Discriminate Different ALS Phenotypes.

Approximately 80-96% of people with amyotrophic lateral sclerosis (ALS) become unable to speak during the disease progression. Assessing upper and lower motor neuron impairment in bulbar regions of ALS patients remains challenging, particularly in distinguishing spastic and flaccid dysarthria. This study aimed to evaluate acoustic voice parameters as useful biomarkers to discriminate ALS clinical phenotypes. Triangular vowel space area (tVSA), alternating motion rates (AMRs), and sequential motion rates (SMRs) were analyzed in 36 ALS patients and 20 sex/age-matched healthy controls (HCs). tVSA, AMR, and SMR values significantly differed between ALS and HCs, and between ALS with prevalent upper (pUMN) and lower motor neuron (pLMN) impairment. tVSA showed higher accuracy in discriminating pUMN from pLMN patients. AMR and SMR were significantly lower in patients with bulbar onset than those with spinal onset, both with and without bulbar symptoms. Furthermore, these values were also lower in patients with spinal onset associated with bulbar symptoms than in those with spinal onset alone. Additionally, AMR and SMR values correlated with the degree of dysphagia. Acoustic voice analysis may be considered a useful prognostic tool to differentiate spastic and flaccid dysarthria and to assess the degree of bulbar involvement in ALS.

The role of exercise parameters on small extracellular vesicles and microRNAs cargo in preventing neurodegenerative diseases.

Physical activity (PA), which includes exercise, can reduce the risk of developing various non-communicable diseases, including neurodegenerative diseases (NDs), and mitigate their adverse effects. However, the mechanisms underlying this ability are not yet fully understood. Among several possible mechanisms proposed, such as the stimulation of brain-derived neurotrophic factor (BDNF), endothelial nitric oxide synthase (eNOS), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), the possible involvement of particular vesicular structures enclosed in lipid membranes known as extracellular vesicles (EVs) has recently been investigated. These EVs would appear to exert a paracrine and systemic action through their ability to carry various molecules, particularly so-called microRNAs (miRNAs), performing a function as mediators of intercellular communication. Interestingly, EVs and miRNAs are differentially expressed following PA, but evidence on how different exercise parameters may differentially affect EVs and the miRNAs they carry is still scarce. In this review we summarized the current human findings on the effects of PA and different exercise parameters exerted on EVs and their cargo, focusing on miRNAs molecules, and discussing how this may represent one of the biological mechanisms through which exercise contributes to preventing and slowing NDs.

Incidence and Long-term Functional Outcome of Neurologic Disorders in Hospitalized Patients With COVID-19 Infected With Pre-Omicron Variants.

BACKGROUND AND OBJECTIVES: A variety of neurologic disorders have been reported as presentations or complications of coronavirus disease 2019 (COVID-19) infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome. METHODS: The Neuro-COVID Italy study was a multicenter, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurologic disorders associated with COVID-19 infection (neuro-COVID), independently from respiratory severity, were systematically screened and actively recruited by neurology specialists in 38 centers in Italy and the Republic of San Marino. The primary outcomes were incidence of neuro-COVID cases during the first 70 weeks of the pandemic (March 2020-June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms, or death. RESULTS: Among 52,759 hospitalized patients with COVID-19, 1,865 patients presenting 2,881 new neurologic disorders associated with COVID-19 infection (neuro-COVID) were recruited. The incidence of neuro-COVID cases significantly declined over time, comparing the first 3 pandemic waves (8.4%, 95% CI 7.9-8.9; 5.0%, 95% CI 4.7-5.3; 3.3%, 95% CI 3.0-3.6, respectively; p = 0.027). The most frequent neurologic disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), and cognitive impairment (13.7%). The onset of neurologic disorders was more common in the prodromic phase (44.3%) or during the acute respiratory illness (40.9%), except for cognitive impairment whose onset prevailed during recovery (48.4%). A good functional outcome was achieved by most patients with neuro-COVID (64.6%) during follow-up (median 6.7 months), and the proportion of good outcome increased throughout the study period (r = 0.29, 95% CI 0.05-0.50; p = 0.019). Mild residual symptoms were frequently reported (28.1%) while disabling symptoms were common only in stroke survivors (47.6%). DISCUSSION: Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic. Long-term functional outcome was favorable in most neuro-COVID disorders, although mild symptoms commonly lasted more than 6 months after infection.

Impact of depression on the perception of fatigue and information processing speed in a cohort of multiple sclerosis patients.

BACKGROUND: Information processing speed is commonly impaired in people with multiple sclerosis (PwMS). However, depression and fatigue can affect the cognitive profile of patients: fatigue has a negative impact from the disease's earliest stage and a reduced information processing speed is often associated with higher levels of depression. Therefore, the aim of this study was to investigate the correlations between information processing speed and physical fatigue in a cohort of Italian PwMS from a single center, considering the effect of depression. METHODS: Two hundred (W = 128; mean age = 39.83 years; SD = 11.86) PwMS, from the Bari University Hospital, underwent testing for processing speed (Symbol Digit Modalities Test [SDMT]), fatigue level (Fatigue Severity Scale [FSS]), and depression (Beck's Depression Inventory [BDI]). RESULTS: Statistically significant correlations emerged between SDMT and FSS, SDMT and BDI, FSS and BDI. Mediation analyses revealed that while physical fatigue had no significant direct negative effect on information processing speed (z=-0.891; p > 0.05), depression predicted the relationship between fatigue and information processing speed (z=-2.181; p < 0.05). CONCLUSION: Our findings showed that cognitive performance at SDMT was not affected by patients' perceived level of physical fatigue, but by depression. The presence of a high BDI score mediates the physical fatigue on cognitive performance impact.

Symptomatic COVID-19 course and outcomes after three mRNA vaccine doses in multiple sclerosis patients treated with high-efficacy DMTs.

BACKGROUND: Little is known about COVID-19 course and outcomes after a third booster dose of mRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response to mRNA-vax. OBJECTIVES: The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCR and FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab (NTZ). METHODS: Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNA-Vax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use. RESULTS: Overall, 290 pwMS (79 NTZ, 126 OCR, and 85 FNG) from 17 Italian MS centers were included. Age, Expanded Disability Status Scale (EDSS) score, MS phenotype, disease, and treatment duration were significantly different across groups. PwMS who had COVID-19 on OCR and FNG compared with those on NTZ were slightly more symptomatic with higher hospitalization rates (11.1% vs 7.1% vs 1.3%, respectively). Regression models showed that the majority of the differences observed were not related to the disease-modifying treatments (DMTs) used. No fatal cases were observed. CONCLUSION: Our results support the effectiveness of the third booster dose of mRNA-Vax against severe forms of COVID-19 in pwMS treated with OCR and FNG.

Patients with multiple sclerosis choose a collaborative role in making treatment decision: results from the Italian multicenter SWITCH study.

BACKGROUND: Clinicians are increasingly recognizing the importance of shared decision-making in complex treatment choices, highlighting the importance of the patient's rationale and motivation for switching therapies. This study aimed to evaluate the association between different modalities of changing multiple sclerosis (MS) treatments, cognitive profile and attitude and preferences of patients concerning treatment choice. METHODS: This multicenter cross-sectional study was conducted at 28 Italian MS centers in the period between June 2016 and June 2017. We screened all MS patients treated with any DMT, with a treatment compliance of at least 80% of therapy administered during the 3 last months who needed to modify MS therapy because of efficacy, safety or other reasons during a follow-up visit. At the time of switching the symbol digit modalities test (SDMT) and the Control Preference Scale (CPS) were evaluated. According to the CPS, patients were classified as "active" (i.e. who prefer making the medical decision themselves), "collaborative" (i.e. who prefer decisions be made jointly with the physician), or "passive" (i.e. who prefer the physician make the decision). RESULTS: Out of 13,657 patients recorded in the log, 409 (3%) changed therapy. Of these, 336 (2.5%) patients, 69.6% were female and with mean age 40.6 ± 10.5 years, were enrolled. According to the CPS score evaluation, a significant high percentage of patients (51.1%) were considered collaborative, 74 patients (22.5%) were passive, and 60 (18.2%) patients were active. Stratifying according to CPS results, we found a higher SDMT score among collaborative patients compared to active and passive ones (45.8 ± 12.3 versus 41.0 ± 13.2 versus 41.7 ± 12.8, p < 0.05). CONCLUSION: In this study, the CPS evaluation showed that more than 50% of patients who needed to change therapy chose a "collaborative" role in making treatment decision. Cognitive profile with SDMT seems to correlate with patients' preference on treatment decision, showing better scores in collaborative patients.

Macular ganglion cell-inner plexiform layer defect patterns in multiple sclerosis patients without optic neuritis: A Spectral-Domain-Optical Coherence Tomography Cross-Sectional, Case-Control, Pilot Study.

PURPOSE: Spectral-domain optical coherence tomography (SD-OCT) was used to evaluate, in patients with multiple sclerosis without a history of optic neuritis (MSNON), the proportion of the different macular ganglion cell-inner plexiform layer complex (mGCIP) defect patterns. The results were compared with those of healthy controls (HCs). METHODS: In this cross-sectional case-control study, 34 eyes of 34 individuals, 17 with MSNON and 17 HCs, were evaluated. All participants underwent mGCIP thickness measurement using SD-OCT (Zeiss Cirrus HD-OCT 4000, macular cube protocol). The mGCIP defect patterns were classified in nine types (minimal, inner, outer, diffuse mild, diffuse severe inferior confined, inferior dominant, superior confined, and superior dominant), according to the shape derived by the deviation map of the instrument, and the proportion of each type was assessed. RESULTS: A mGCIP defect pattern was detected in 70.5% of MSNON eyes, with an inner type as the most frequent pattern (47%), followed by the outer type (11.7%) and the inferior confined type (11.7%). No defect was found in Hcs. CONCLUSIONS: A significant thinning of the mGCIP with the frequent presence of an inner defect was seen in MSNON patients. The presence of this defect may serve as a biomarker of subclinical optic nerve involvement in MS patients.

Real-Life Experience of the Effects of Cladribine Tablets on Lymphocyte Subsets and Serum Neurofilament Light Chain Levels in Relapsing Multiple Sclerosis Patients.

Although cladribine induces sustained reductions in peripheral T and B lymphocytes, little is known about its effect on axonal damage reduction in multiple sclerosis (MS), which could be demonstrated by assessing the serum neurofilament light chain (sNfL) levels. We investigated the reduction/reconstitution of different lymphocyte subsets (LS) by verifying the correlation with no evidence of disease activity (NEDA) and the variation in sNfL levels during cladribine treatment. We analysed 33 highly active relapsing MS patients and followed them up for 12 ± 3.3 months; blood samples were collected at treatment start (W0) and after 8, 24 and 48 weeks. Seventeen patients (60.7%) showed NEDA during the first treatment. At week 8, we observed a significant decrease in B memory cells, B regulatory 1 CD19+/CD38+ and B regulatory 2 CD19+/CD25+, a significant increase in T regulatory CD4+/CD25+, a slight increase in T cytotoxic CD3+/CD8+ and a non-significant decrease in T helper CD3+/CD4+. Starting from week 24, the B subsets recovered; however, at week 48, CD19+/CD38+ and CD19+/CD25+ reached values near the baseline, while the Bmem were significantly lower. The T cell subsets remained unchanged except for CD4+/CD25+, which increased compared to W0. The LS changes were not predictive of NEDA achievement. The sNfL levels were significantly lower at week 24 (p = 0.046) vs. baseline. These results could demonstrate how cladribine, by inflammatory activity depletion, can also reduce axonal damage, according to the sNfL levels.

A nurse-led, telephone-based patient support program for improving adherence in patients with relapsing-remitting multiple sclerosis using interferon beta-1a: Lessons from a consumer-based survey on adveva® PSP.

Background: Evidence suggests that organizational models that provide care interventions including patient support programs may increase patient adherence to multiple sclerosis (MS) therapies by providing tailored symptom management, informational support, psychological and/or social support, lifestyle changes, emotional adjustment, health education, and tailored coaching, thus improving patients' overall quality of life across the disease course. Objective: The main objective of this study was to describe MS patients' self-reported experience of a nurse-led, telephone-based PSP and to explore its potential role in improving disease and therapy management skills. Methods: Survey data were analyzed from a subset of patients relapsing-remitting MS (RRMS) using interferon beta-1a already registered in the adveva® PSP from three Italian multiple sclerosis centers with a consolidated experience in RRMS disease, treatment management, and PSP programs. Results: In total, 244 patient data at baseline were analyzed, of which 115 had a follow-up of at least 6 months. Results from this study provide an early view into the role of this PSP in improving the patients reported overall experience regarding disease management and injectable therapy, thus potentially ameliorating treatment adherence and decreasing health care cost. Moreover, study findings confirm the role of providing a patient-focused support by addressing non-medication-related topics in the PSP consultations. Indeed, patients involved in the adveva® PSP program reported a better psychological status in the follow up as demonstrated by an increased optimism regarding their future, tolerance of disease uncertainty, and their perceived ability to benefit from external help and social support (informal caregivers). Conclusions: As such, it is reasonable to conclude that the involvement in the adveva® PSP and the PSP's assistance in guiding patients on proper treatment self-management techniques is of great value to patients as it might contribute to improving engagement in their health care journey in terms of perceived self-care skills, emotional coping toward the future and the unpredictability of the disease course and their general attitudes toward the injection itself, involving pain tolerance.

Towards a validated definition of the clinical transition to secondary progressive multiple sclerosis: A study from the Italian MS Register.

BACKGROUND: Definitions for reliable identification of transition from relapsing-remitting multiple sclerosis (MS) to secondary progressive (SP)MS in clinical cohorts are not available. OBJECTIVES: To compare diagnostic performances of two different data-driven SPMS definitions. METHODS: Data-driven SPMS definitions based on a version of Lorscheider's algorithm (DDA) and on the EXPAND trial inclusion criteria were compared, using the neurologist's definition (ND) as gold standard, in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Akaike information criterion (AIC) and area under the curve (AUC). RESULTS: A cohort of 10,240 MS patients with ⩾5 years of follow-up was extracted from the Italian MS Registry; 880 (8.5%) patients were classified as SPMS according to the neurologist definition, 1806 (17.6%) applying the DDA and 1134 (11.0%) with the EXPAND definition. The DDA showed greater discrimination power (AUC: 0.8 vs 0.6) and a higher sensitivity (77.1% vs 38.0%) than the EXPAND definition, with similar specificity (88.0% vs 91.5%). PPV and NPV were higher using the DDA than considering EXPAND definition (37.5% vs 29.5%; 97.6% vs 94.0%). CONCLUSION: Data-driven definitions demonstrated greater ability to capture SP transition than neurologist's definition and the global accuracy of DDA seems to be higher than the EXPAND definition.

Cost-utility analysis of teriflunomide in naïve vs. previously treated patients with relapsing-remitting multiple sclerosis in Italy.

BACKGROUND: Multiple sclerosis (MS) accounts for 176 cases per 100,000 inhabitants (female/male ratio = 2:1) in Italy. For most of the patients (67%), the disease course is relapsing-remitting MS (RRMS). OBJECTIVE: To compare the costs and quality-adjusted life years (QALYs) of teriflunomide in RRMS naïve patients vs. RRMS patients previously treated (experienced) with other disease-modifying therapies in Italy. METHODS: A four health states Markov model-supported cost-utility analysis (CUA) covering a 7-year timespan through annual cycles was developed, following the healthcare sector and the societal viewpoints. Part of the parameters that populated the Markov model was obtained from a questionnaire administered to four primary Italian MS centres. Costs of healthcare and non-healthcare resources, expressed in euro (€) 2019, and QALYs were discounted at 3% real social discount rate. One-way, scenario and probabilistic sensitivity analyses tested the uncertainty of the baseline findings. RESULTS: Baseline CUA shows that teriflunomide in RRMS naïve patients is strongly dominant vs. experienced patients (healthcare sector perspective: - €1042.68 and + 0.480 QALYs; societal perspective: - €6782.81 and + 0.480 QALYs). Sensitivity analyses confirmed the robustness of the baseline results. CONCLUSION: Teriflunomide in RRMS naïve vs. experienced patients is cost-effective and possibly strongly dominant from both the healthcare sector and the society viewpoints in Italy. Our findings need further confirmation from real-world studies.

Predictors of unemployment status in people with relapsing multiple sclerosis: a single center experience.

BACKGROUND: Multiple sclerosis (MS) is the most common cause of nontraumatic chronic neurological disability affecting young adults during their crucial employment years. OBJECTIVES: To evaluate patients and disease related factors associated to unemployment in a cohort of relapsing-remitting (RR) MS patients. METHODS: We included RRMS patients with a follow-up of at least 1 year. We collected data about years of school education and employment status. Patients underwent a neuropsychological evaluation using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Demographic and clinical predictors of unemployment were assessed through a multivariable stepwise logistic regression model. RESULTS: We evaluated 260 consecutive RRMS patients. Employed patients were less frequently female (68.4% vs 83.3%, p = 0.006), less disabled (median Expanded Disability Status Scale (EDSS) score: 2.0 (0-7.0) vs 2.5 (0-7.5), p < 0.001), with more years of school education (mean ± standard deviation (SD), years: 13.74 ± 0.30 vs 10.86 ± 3.47, p < 0.001). Female sex and a higher EDSS score resulted associated with a greater risk of unemployment (OR 3.510, 95% CI 1.654-7.448, p = 0.001; OR 1.366, 95% CI 1.074-1.737, p = 0.011, respectively), whereas a greater number of years of schooling and current disease-modifying therapy exposure resulted protective factors (OR 0.788, 95% CI 0.723-0.858, p < 0,001; OR 0.414, 95% CI 0.217-0.790, p = 0.008, respectively). CONCLUSIONS: Understanding work is pervasively influenced by consequences of MS, we confirmed the impact of demographic, physical, and cognitive factors on employment status in RRMS patients.

Natalizumab treatment and pregnancy in multiple sclerosis: A reappraisal of maternal and infant outcomes after 6 years.

OBJECTIVES: To assess the impact of timing of natalizumab cessation/redosing on long-term maternal and infant outcomes in 72 out of the original 74 pregnancies of the Italian Pregnancy Dataset in multiple sclerosis (MS). METHODS: Maternal outcomes in patients who received natalizumab until conception and restarted the drug within 1 month after delivery ("treatment approach," (TA)) and patients who stopped natalizumab before conception and/or restarted the drug later than 1 month after delivery ("conservative approach," (CA)) were compared through multivariable Cox regression analyses. Pediatric outcomes were assessed through a semi-structured questionnaire. RESULTS: After a mean follow-up of 6.1 years, CA (hazard ratio (HR) = 4.1, 95% CI 1.6-10.6, p = 0.003) was the only predictor of relapse occurrence. Worsening on the Expanded Disability Status Scale (EDSS) was associated with higher annualized relapse-rate during the follow-up (HR = 3.3, 95% CI 1.4-7.9 p = 0.007). We found no major development abnormalities in children. DISCUSSION: Our data confirm that TA reduces the risk of disease activity; we did not observe an increase in major development abnormalities in the child.