Quality of care provided by Multiple Sclerosis Centers during Covid-19 pandemic: Results of an Italian multicenter patient-centered survey.

BACKGROUND: Covid-19 pandemic impacted on management of people with Multiple Sclerosis (pwMS). Level of satisfaction of pwMS regarding the care received by the staff of Multiple Sclerosis Centers (MSCs) during the pandemic was not fully investigated. In a large patient-centered multicenter study, the therapeutic adherence and quality of care of MSCs was assessed. METHODS: In April-May 2021, an online survey was widespread by 16 Italian MSCs. Frequencies, percentages and/or means and standard deviations were calculated to describe the sample. ANOVAs were performed to evaluate the effect of sociodemographic and clinical variables on overall pwMS' rating of MSC assistance. RESULTS: 1670 pwMS completed the survey (67.3% women). During the pandemic, 88% did not change their disease modifying therapy schedule, and 89.1% reached their MSCs with no or little difficulties. Even if only 1.3% of participants underwent a tele-health follow-up visit with their MSC staff, the 80.1% believed that tele-health services should be improved regardless of pandemic. 92% of participants were satisfied of how their MSC took charge of their needs; ANOVAs revealed an effect of disease duration on pwMS' level of satisfaction on MSCs management during the pandemic. CONCLUSIONS: The results revealed an efficient MSCs response to Covid-19 pandemic and provided the basis for the implementing of tele-health services that would further improve the taking charge of patients, particularly those with longer disease, higher disability, and/or living far from their MSC.

The Utility of Delta-9-Tetrahydrocannibinol Therapy in a Multiple Sclerosis Patient with a Neoplastic Brain Lesion.

Multiple sclerosis (MS) can sometimes cause uncommon pseudotumoural lesions that produce atypical symptoms, such as motor epileptic seizures which are often pharmacoresistant. In these cases, accurate diagnosis is essential for correct therapy, even if unconventional. We present the case of a brain tumour in a 40-year-old relapsing-remitting MS patient who presented with pharmacoresistant seizures which eventually responded to nabiximols. After various therapeutic approaches, delta-9-tetrahydrocannabinol therapy was introduced with good results. Spasticity improved, pain decreased and we observed a reduction in the number of daily seizures. It is possible that delta-9-tetrahydrocannabinol can enhance the efficacy of anti-epilepsy therapy. LEARNING POINTS: The patient experienced fewer daily focal motor crises after the administration of nabiximols in the morning.The correct combination of symptomatic drugs can optimize a specific multiple sclerosis (MS) therapy even if the real cause of symptoms is a primary brain tumour and not MS.The addition of nabiximols to the therapeutic program allowed anti-epilepsy drug doses to be reduced and improved the patient's cognitive impairment.

Early prediction of the long term evolution of multiple sclerosis: the Bayesian Risk Estimate for Multiple Sclerosis (BREMS) score.

AIM: To propose a simple tool for early prediction of unfavourable long term evolution of multiple sclerosis (MS). METHODS: A Bayesian model allowed us to calculate, within the first year of disease and for each patient, the Bayesian Risk Estimate for MS (BREMS) score that represents the risk of reaching secondary progression (SP). RESULTS: The median BREMS scores were higher in 158 patients who reached SP within 10 years compared with 1087 progression free patients (0.69 vs 0.30; p<0.0001). The BREMS value was related to SP risk in the whole cohort (p<0.0001) and in the subgroup of 535 patients who had never been treated with immune therapies, thus reasonably representing the natural history of the disease (p<0.000001). CONCLUSIONS: The BREMS score may be useful both to identify patients who are candidates for early or for more aggressive therapies and to improve the design and analysis of clinical therapeutic trials and of observational studies.

Age-related gadolinium-enhancement of MRI brain lesions in multiple sclerosis.

There is evidence that inflammatory processes in multiple sclerosis (MS) are age-dependent. In this study we evaluated the impact of aging on gadolinium (Gd) enhancement of brain magnetic resonance imaging (MRI) lesions in MS patients. Pre- and post-contrast MRI scans, acquired using a standardized procedure by the same MRI scanner, at least 1 month far from clinical relapse or steroid treatment, were examined in 200 disease-modifying treatment free MS patients. Seventy-three patients (36.5%) showed at least one enhancing lesion. Age at MRI examination (p=0.0001), disease duration (p=0.002) and EDSS score were significantly (p=0.02) lower, whereas relapse rate in the preceding 2 years was higher (p=0.003) in patients with enhancing lesions than in patients with unenhancing scans. Multivariate logistic analysis showed that current age was the variable better predicting Gd enhancement (p=0.004). The odds ratios were 0.95 (CI: 0.92-0.98) for each year of patient's age and 0.64 (CI: 0.48-0.87) for each age decade. The main changes in enhancement risk occurred after 35 years of age. Multivariate Poisson regression model showed that relapse rate in the preceding 2 years (p<0.0001) and current age (p=0.0003) were the best predictors of the number of enhancing lesions. This information can be used to increase the statistical power of clinical trials using Gd-enhancing lesions as an outcome measure.

Fingolimod Treatment in Relapsing-Remitting Multiple Sclerosis Patients: A Prospective Observational Multicenter Postmarketing Study.

Objective. The aim of this prospective observational multicenter postmarketing study was to evaluate fingolimod efficacy in a real world clinical setting. Methods. One hundred forty-two subjects with relapsing-remitting multiple sclerosis (RRMS) were enrolled in three multiple sclerosis centers throughout Central and Southern Italy between January 2011 and September 2013. After enrollment, regular visits and EDSS assessment were scheduled every 3 months, and MRI scan was obtained every 12 months. Patients were followed up from 1 to 33 months (mean 14.95 ± 9.15 months). The main efficacy endpoints included the proportion of patients free from clinical relapses, from disability progression, from magnetic resonance imaging activity, and from any disease activity. Results. Out of 142 patients enrolled in the study, 88.1% were free from clinical relapse and 69.0% were free from disability progression; 68.5% of patients remained free from new or newly enlarging T2 lesions and 81.7% of patients were free from gadolinium enhancing lesions. Overall the proportion of patients free from any disease activity was 41.9%. Conclusions. Our data in a real world cohort are consistent with previous findings that yield convincing evidence for the efficacy of fingolimod in patients with RRMS.

Postmarketing evidence of disease-modifying drugs in multiple sclerosis.

There is growing interest in the use of observational data to estimate treatment effects in chronic diseases such as multiple sclerosis (MS). The main results derived from postmarketing evaluations, in the last 2 years, of short-and long-term disease modifying drugs (DMDs) effectiveness will be reported in this Review. Moreover, some of the methodological improvements that may be useful to enhance the quality of observational studies will also be discussed.

New natural history of interferon-beta-treated relapsing multiple sclerosis.

OBJECTIVE: To investigate the impact of interferon-beta (IFNbeta) on disease progression in relapsing-remitting multiple sclerosis patients. METHODS: A cohort of 1,504 relapsing-remitting multiple sclerosis (1,103 IFNbeta-treated and 401 untreated) patients was followed for up to 7 years. Cox proportional hazards regression adjusted for propensity score inverse weighting was used to assess the differences between the two groups for three different clinical end points: secondary progression (SP) and irreversible Expanded Disability Status Scale (EDSS) scores 4 and 6. Times from first visit and from date of birth were used as survival time variables. RESULTS: The IFNbeta-treated group showed a highly significant reduction in the incidence of SP (hazard ratio [HR], 0.38, 95% confidence interval [CI], 0.24-0.58 for time from 1st visit; HR, 0.36, 95% CI, 0.23-0.56 for time from date of birth; p < 0.0001), EDSS score of 4 (HR, 0.70, 95% CI, 0.53-0.94 for time from first visit; HR, 0.69, 95% CI, 0.52-0.93 for time from date of birth; p < 0.02), and EDSS score of 6 (HR, 0.60, 95% CI, 0.38-0.95 for time from first visit; HR, 0.54, 95% CI, 0.34-0.86 for time from date of birth; p < or = 0.03) when compared with untreated patients. SP and EDSS scores of 4 and 6 were reached with significant delays estimated by times from first visit (3.8, 1.7, and 2.2 years) and from date of birth (8.7, 4.6, and 11.7 years) in favor of treated patients. Sensitivity analysis confirmed findings. INTERPRETATION: IFN-beta slows progression in relapsing-remitting multiple sclerosis patients.

The Italian Multiple Sclerosis Database Network (MSDN): the risk of worsening according to IFNbeta exposure in multiple sclerosis.

We evaluated the risk of worsening according to the length of exposure to interferon beta (IFNbeta) in a large cohort of 2090 multiple sclerosis patients collected by the Italian MS Database Network. Overall 44,140 patient-visits with a follow-up of 22,143 patient-years were evaluated. Forty-one per cent of patients were exposed to IFNbeta for up to 2 years, 39% for 2-4 years and 20% for more than 4 years. A Cox regression model was used to analyse two clinical outcomes: disability progression and worsening of relapse rate. The technique of propensity score was applied to reduce bias in the comparison of non-randomized groups. The risks of disability progression (HR =0.23; 95% CI: 0.17-0.30) and worsening of relapse rate (HR =0.19; 95% CI: 0.14-0.27) were reduced by about 4-5-fold in patients exposed to IFNbeta for more than four years, compared with patients exposed for up to two years. The propensity score technique confirmed the findings. The proportion of days covered by IFNbeta treatment was lower (P <0.0001) in patients exposed to IFNbeta for up to two years than in other groups. A clinical stabilization over two years of IFNbeta exposure may predict a subsequent good clinical response to treatment.

Interferon beta in relapsing-remitting multiple sclerosis: an independent postmarketing study in southern Italy.

This independent, population-based surveillance study monitored the efficacy and safety of interferon beta (IFNbeta) products in 1033 patients with relapsing-remitting multiple sclerosis (RRMS) from 15 centres in Italy. Relapses, Expanded Disability Status Scale (EDSS) scores, and adverse events were evaluated for up to 24 months. Data of patients with a baseline EDSS score < or = 3.5 are reported. The proportions of relapse-free patients were similar among the groups at 12 and 24 months (P = 0.10). IFNbeta products produced significant reductions from baseline in relapse rates at 12 and 24 months (P < 0.001), with no differences among treatments (P = 0.2). There were no significant differences in mean EDSS change among groups at 12 or 24 months. The IFNbeta-1b group showed a higher incidence of adverse events during the first year of treatment (P < 0.05) than IFNbeta-1a groups, and more withdrawals (10%) compared with Avonex (5%) at 24 months. IFNbeta products are equally effective in low disability RRMS, but IFNbeta-1a may have a more favorable efficacy/tolerability ratio.