Background The 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. Methods We 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. Results A 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%). Conclusions Sativex can be a useful and safe option for patients with MS with moderate to severe spasticity resistant to common antispastic drugs.

Importance: Natalizumab discontinuation induces the recurrence of Multiple Sclerosis (MS) disease activity: Currently no therapeutic approach has been found able to abolish disease reactivation. Objective: To collect data from patients with MS switching from natalizumab to cyclophosphamide. Design: Retrospective multicentre study. Setting: Nine Multiple Sclerosis Centers in Italy. Participants: A total of 47 patients with clinically definite RR-MS switched to cyclophosphamide after natalizumab discontinuation. Two patients were excluded from the analysis because received less than 12 natalizumab infusions. The remaining 45 patients were subdivided into two main groups: Early Treatment (period of washout between natalizumab and cyclophosphamide 1 to 3 months), Late Treatment (washout between natalizumab and cyclophosphamide higher than 3 months). Intervention: Cyclophosphamide intravenous pulses after natalizumab discontinuation. Main outcome measure: Number of relapses, Expanded Disability Status Scale scores, number of new T2/fluidattenuated inversion recovery lesions and contrast-enhancing lesions on brain magnetic resonance imaging, rebound effect, adverse events. Results: In the Early Treatment group, only 3/23 patients (13%) experienced a clinical relapse and only 2 out of 13 (15%) patients showed brain Magnetic Resonance Imaging (MRI) activity at 3 months, while none developed MRI activity at 6 months after cyclophosphamide introduction. In the Late Treatment Group 12/22 patients (63%) had relapses during the washout period and 4/22 (40%) after the introduction of cyclophosphamide; MRI disease activity was shown in 5/9 (56%) at 3 months and in 5/14 (36%) at 6 months after cyclophosphamide introduction. Conclusions and relevance: These data show that cyclophosphamide could be able to reduce disease reactivation after natalizumab, in particular with a short washout period after natalizumab discontinuation. It can be suggested that a short period (3-6 months) of cyclophosphamide monthly pulses could be used as “re-induction” treatment in patients discontinuing natalizumab.

Objective:The aim of this study was to compare the efficacy of natalizumab and fingolimod in relapsing-remitting multiple sclerosis patients in real-world clinical setting. Methods:We enrolled 391 patients starting either natalizumab or fingolimod for relapsing-remitting multiple sclerosis, referred to four multiple sclerosis centers between March 2007 and July 2013.Cumulative proportion of patients free from any disease activity, as defined by freedom from relapse, Expanded Disability Status Scale (EDSS) progression, new or newly enlarging T2 lesions, and gadolinium enhancing lesions at magnetic resonance imaging (MRI) was assessed at 12-month follow-up.Results: Out of 391 patients, 197 were treated with natalizumab and 194 with fingolimod.The cumulative proportion of patients free from any disease activity was 72.0% in the natalizumab and 59.1% in the fingolimod group (P=0.014).This proportion was lower in fingolimod patients with prior natalizumab exposure compared to those without (51.7% vs. 61.8%;P=0.008).Moreover, the cumulative proportion of patients free from new MRI lesions was 87.5% in the natalizumab vs. 70.0% in the fingolimod group (P<0.001); the cumulative proportion of patients free from clinical relapse was 82.5% in the natalizumab vs. 81.3% in the fingolimod group (P=0.739);93.5% of patients on natalizumab were free from EDSS progression compared to 89.6% of patients on fingolimod (P=0.186). Conclusions:Results from 1-year follow-up of treatment suggest higher efficacy of natalizumab compared to fingolimod in terms of proportion of patients free from any disease activity.

We evaluated efficacy of natalizumab in relapsing-remitting multiple sclerosis patients in a clinical practice setting. We report data on the first consecutive 343 patients receiving natalizumab in 12 multiple sclerosis (MS) Italian centers enrolled between April 2007 and November 2010. The main efficacy endpoints were the proportion of patients free from relapses, disease progression, combined clinical activity, defined as presence of relapse or disease progression, from MRI activity, and from any disease activity defined as the absence of any single or combined activity. At the end of follow-up, the cumulative proportion of patients free from relapses was 68%; the proportion of patients free from Expanded Disability Status Scale (EDSS) progression was 93%; the proportion of patients free from combined clinical activity was 65%; the proportion of patients free from MRI activity was 77%; and the proportion of patients free from any disease activity was 53%. Natalizumab was effective in reducing clinical and neuroradiological disease activity. Its effectiveness in clinical practice is higher than that reported in pivotal trials and was maintained over time.