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Rituximab (RTX) efficacy in NMO is suggested by several case series. No consensus exists on optimal dosing strategies. At present the treatment schedules more frequently used are 375 mg/m2/week iv for 4 weeks (RTX-A) and 1000 mg iv twice, 2 weeks apart (RTX-B). Aim of this study is to confirm RTX efficacy and safety in the treatment of NMO and to evaluate whether a most favourable dosage regimen exists. Data on RTX-treated NMO patients were collected from 13 Italian Hospitals. 73 patients (64 F), were enlisted. RTX-A was administered in 42/73 patients, RTX-B in 31/73. Median follow-up was 27 months (range 7–106). Mean relapse rate in the previous year before RTX start was 2.2 ± 1.3 for RTX-A and 2.3 ± 1.2 for RTX-B. ARR in the first year of treatment was 0.8 ± 0.9 for RTX-A and 0.2 ± 0.4 for RTX-B, in the second year of treatment was 0.9 ± 1.5 for RTX-A and 0.4 ± 0.8 for RTX-B patients ( p  = 0.001 for the first year, ns (0.09) for the second year). RTX-B was more effective in delaying the occurrence of a relapse (HR 2.2 (95 % IC 1.08–4.53) p  = 0.02). Adverse events were described in 19/73 patients (mainly urinary tract and respiratory infections, and infusion reactions). Two deaths were reported in severely disabled patients. Though with the limitations of an observational study, our data support RTX efficacy in NMO and suggest that high dose pulses might be more effective than a more fractioned dose.

BackgroundThe approval of 9-δ-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex) for the management of treatment-resistant multiple sclerosis (MS) spasticity opened a new opportunity for many patients. The aim of our study was to describe Sativex effectiveness and adverse events profile in a large population of Italian patients with MS in the daily practice setting.MethodsWe collected data of all patients starting Sativex between January 2014 and February 2015 from the mandatory Italian medicines agency (AIFA) e-registry. Spasticity assessment by the 0–10 numerical rating scale (NRS) scale is available at baseline, after 1 month of treatment (trial period), and at 3 and 6 months.ResultsA total of 1615 patients were recruited from 30 MS centres across Italy. After one treatment month (trial period), we found 70.5% of patients reaching a ≥20% improvement (initial response, IR) and 28.2% who had already reached a ≥30% improvement (clinically relevant response, CRR), with a mean NRS score reduction of 22.6% (from 7.5 to 5.8). After a multivariate analysis, we found an increased probability to reach IR at the first month among patients with primary and secondary progressive MS, (n=1169, OR 1.4 95% CI 1.04 to 1.9, p=0.025) and among patients with >8 NRS score at baseline (OR 1.8 95% CI 1.3–2.4 p<0.001). During the 6 months observation period, 631(39.5%) patients discontinued treatment. The main reasons for discontinuation were lack of effectiveness (n=375, 26.2%) and/or adverse events (n=268, 18.7%).ConclusionsSativex can be a useful and safe option for patients with MS with moderate to severe spasticity resistant to common antispastic drugs.

The Multiple Sclerosis Database Network (MSDN) is the first Italian multiple sclerosis (MS) registry. The preliminary results on the MSDN cohort demonstrated that the risk of disability progression, in a sample of 2090 MS patients, was reduced by about four- to five-fold in patients exposed to IFNbeta for more than 4 years compared with patients exposed for up to 2 years. More recent results showed, in a subset of 1170 relapsing-remitting MS patients, of whom 918 were treated with IFNbeta and 252 were untreated, that IFNbeta-treated patients had a differential reduction in EDSS score change of -0.055 for each year of follow-up in comparison with the untreated group. These results provide significant information on the effectiveness of IFNbeta treatment on long-term disability progression in MS.

Multiple sclerosis (MS) patients complain with the first symptoms of the disease in a range period which varies from childhood to adult life. The extent to which clinical presentation, disease course and demographic features may differ between childhood and adult onset has been the object of investigation. This paper aims to demonstrate that the different clinical phenotypes in young and old patients might simply reflect different phases of a same pathological process.

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.

Introduction Multiple sclerosis (MS) is a highly symptomatic disease, with a wide range of disabilities affecting many bodily functions, even in younger persons with a short disease history. The availability of a cannabinoid oromucosal spray (Sativex) for the management of treatment-resistant MS spasticity has provided a new opportunity for many patients. Objective Our study aimed to assess the cost effectiveness of Sativex in Italian patients with treatment-resistant MS spasticity. The analysis was based on the real-world data of a large registry of Italian patients. Methods A cost-utility analysis was conducted using data collected prospectively from an electronic registry of all patients who began to use Sativex for MS-resistant spasticity between January 2014 and February 2015 in 30 specialized MS units across Italy and were followed up for ≤ 6 months. Data on drug consumption and spasticity/utility were used to estimate the incremental cost-effectiveness ratio (ICER) of Sativex, as compared with no intervention. No costs or spasticity/utility changes were assumed for no treatment intervention. The ICER was expressed as quality-adjusted life-years (QALYs) gained, using the Italian NHS perspective and a 6-month time horizon. Results Sativex effectiveness and consumption was estimated analyzing data of 1350 patients from the registry. These patients reported a mean (SD) utility increment of 0.087 (0.069) after 1 month of treatment, 0.118 (0.073) after 3 months’ treatment and 0.127 (0.080) after 6 months’ treatment. The 6-month cost of treating the entire population with Sativex was €1,361,266, with a €1008 cost and 0.0284 QALYs gained per patient. The estimated ICER was €35,516 per QALY gained, with little variability around the central estimate of cost-effectiveness, as shown by the cost-effectiveness acceptability curve. Conclusion The use of Sativex could improve the quality of life of patients with a reasonable incremental cost resulting as a cost-effective option for patients with MS-resistant spasticity. These results could help clinicians and decision makers to develop improved management strategies for spasticity in patients with MS, optimizing the use of available resources.

AbstractAbstract This independent, population-based surveillance study monitored, in clinical practice, the efficacy of interferon beta (IFNβ) products in 1173 patients with multiple sclerosis (MS) from the Department of Neurological and Psychiatric Sciences, University of Bari, Italy. Relapses and Expanded Disability Status Scale (EDSS) scores were evaluated for up to 6 years for Avonex, Betaferon and Rebif 22 groups, and for up to 3 years for the Rebif 44 group. IFNβ products produced significant reductions from baseline in relapse rates at 2, 4 and >4 years (p<0.0001), with no differences among treatments (p=0.2). A modest significant (p<0.05) increase of EDSS was observed in all treatment groups from baseline to 48 months, followed thereafter by a plateau. The IFNβ-1b group showed more withdrawals (19%) compared with Avonex (6%) and Rebif (7%) at 6 years.

This independent, population-based surveillance study monitored the efficacy and safety of interferon beta (IFNb) 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 5-3.5 are reported. The proportions of relapse-free patients were similar among the groups at 12 and 24 months (P =0.10). IFNb products produced significant reductio ns from baseline in relapse rates at 12 and 24 months (P B-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 IFNb-1b group showed a higher incidence of adverse events during the first year of treatment (P B-0.05) than IFNb-1a groups, and more withdrawals (10%) compared with Avonex (5%) at 24 months. IFNb products are equally effective in low disability RRMS, but IFNb-1a may have a more favorable efficacy/tolerability ratio.

Background: The impact of Neutralizing antibodies (NAbs) on interferon beta (IFN beta ) efficacy in multiple sclerosis (MS) patients is still object of controversy, therefore there is insufficient information on the utilization of NAb testing in clinical decisions. Objective: To evaluate, in clinical practice, on a large population of relapsing-remitting (RR) MS patients followed up to 5 years, the different clinical response to IFN beta during NAb-positive and NAb-negative statuses. Methods: Sera of 556 RRMS patients treated with IFN beta for a period ranging between 2 and 5 years were longitudinally collected every six to twelve months and evaluated for the presence of NAbs by a cytopathic effect (CPE) assay. Neurological examination by Expanded Disability Status Scale (EDSS) and relapses were scheduled every six months. A patient's NAb-positive status was defined after two consecutive positive titers of NAbs >/= 20 neutralizing units (NU)/mL. Multivariate time-dependent Poisson and Cox models were respectively used to analyze the relapse rate and time to confirmed EDSS score 4 between NAb-positive and NAb-negative statuses. A propensity score (PS) matching analysis, adjusted to the time at which the comparator group first became positive, was performed to assess the robustness of the multivariate models. Results: Fourteen per cent of patients became NAb-positive during the follow-up. A significant increase in relapse rate (IRR=1.39; p=0.0076) was found during the NAb-positive in comparison with NAb-negative periods. PS matching analysis confirmed this significant difference (IRR=1.48; p=0.04) and showed a significant trend to a higher risk in time to confirmed EDSS 4.0 (IRR=2.29; p=0.06) during the NAb-positive periods. Conclusions: This post-marketing survey on a large cohort of RRMS patients confirmed a reduced effectiveness of IFN beta with respect to the disease activity due to NAb positivity. Moreover, an unfavorable effect of NAbs on long-term disability progression was also demonstrated, suggesting that NAb testing may be useful in therapeutic decisions.

Background: Little is known on pregnancy outcome after in utero exposure to beta-interferon (IFNB) therapy. Objective: To assess the impact of IFNB therapy on pregnancy outcomes in an Italian cohort of multiple sclerosis (MS) patients. Methods: We recruited MS patients (both women and men), followed-up in 14 Italian MS Centres, for whom a pregnancy was recorded in the period 1996-2007. Patients were divided into 3 groups: drug-exposed pregnancies (EP: suspension of the drug<1 month prior to conception); non-exposed pregnancies (NEP: suspension of the drug>1 month prior to conception) and never treated pregnancies (NTP). All the patients were administered a structured interview which gathered detailed information on pregnancy course and outcomes, as well as on possible confounders. Multivariate logistic and linear models were used for treatment comparisons. Furthermore, propensity score (PS) adjusted logistic and linear models were assessed. Results: Data on 432 pregnancies were collected (364 in women, 68 in men). Among women, 82 were classified as EP to IFNB, 97 as NEP, and 160 as NTP. Pregnancies resulted in 72 live births and 10 non-live births in the EP, 90 live births and 7 non-live births in the NEP, 155 live births and 5 non-live births in the NTP. IFNB exposure was not significantly related to spontaneous abortion (OR=0.99; 95%CI 0.29-3.37; p=0.98) whereas it was associated with a higher frequency of preterm delivery (OR=1.94; 95%CI 1.04-3.61; p=0.037), and lower weight (p<0.0001) and length (p<0.0001) of the child. These findings were confirmed in the PS-adjusted models. Considering pregnancy and fetal outcomes in the 63 men (31 exposed to IFNB, 32 non-exposed), we did not observe significant differences between EP and NEP. Conclusions: Data in our cohort show that the mother's IFNB exposure is associated with a lower child's weight and length, whereas IFNB does not seem to be associated with a higher frequency of spontaneous abortion.