Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Assessing apathy in multiple sclerosis: Validation of the dimensional apathy scale and comparison with apathy evaluation scale.

BACKGROUND: Apathy is a predictor of cognitive decline in the course of multiple sclerosis (MS). Early identification of apathetic patients is relevant in clinical settings. OBJECTIVE: To assess applicability and psychometric properties of the self-rated version of the Dimensional Apathy Scale (DAS) in a large cohort of patients with MS and to compare its diagnosing accuracy with that of the Apathy Evaluation Scale (AES). METHODS: One hundred and twenty-four patients underwent clinical interview based on diagnostic criteria for apathy, DAS, AES, and assessment of depression, global cognitive functioning, and non-verbal intelligence. RESULTS: According to diagnostic criteria, apathy occurred in 33.4% of the patients. The DAS showed high consistency, and good convergent, discriminant and criterion validity. Factor analysis indicated a three-factor structure: executive, behavioural and emotional apathy. Unlike AES, no significant association between DAS score and severity of neurological disability (expressed by EDSS total score) was found, suggesting that the DAS might be less related to levels of disability. Receiver operating characteristics analyses, with clinical diagnostic criteria for apathy as the gold standard, revealed that a DAS score of 28/29 and an AES score of 35/36 were optimal cut-off values for identifying clinically relevant apathy. The two scales had similar diagnostic accuracy in the present sample. CONCLUSIONS: The DAS is a valid and reliable multidimensional tool to assess apathy in MS, with diagnostic accuracy similar to that of the AES. However, the DAS score appears to be less strongly related to neurological disability.

Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity.

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.

Biomechanical behaviour of a jawbone loaded with a prosthetic system supported by monophasic and biphasic implants.

Modern implantology is based on the use of endosseous dental implants and on the study of osseointegration processes. The loss of marginal bone around a dental implant can be caused by many factors; the proper distribution of the masticatory loads is important and is closely dependent on the quality and quantity of bone tissue surrounding the implant. In fact, bone has the ability to adapt its microstructure, through processes of resorption and neoformation of new bone matrix, as a result of the mechanical stimuli that are generated during the chewing cycles. The purpose of this article is to redefine in a modern key and in light of current industrial and engineering technology, clinical and biomechanical concepts that characterize the monophasic implants, in order to assess proper use by evaluating the biomechanical differences with the biphasic implants.

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

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.

[Post-gastrectomy Wernicke-Korsakoff syndrome: clinical study of 2 cases]. / Sindrome di Wernicke-Korsakoff post gastrectomia: studio clinico di due casi.

The Authors present two cases of Wernicke-Korsakoff Disease following gastric surgery. This clinical occurrence hasn't been previously described in Literature. The pathogenetical role of nutritional factors deficiency is discussed.

Cerebral blood flow in thalamic aphasia.

A 59-year-old man is reported, who became aphasic after left thalamic infarction, shown by CT. His speech was fluent, with reduced voice volume, impaired auditory and reading comprehension, verbal paraphasias but intact repetition skills. A single photon emission computed tomography (SPECT) scan to measure regional cerebral flow (rCBF) showed a reduction of flow in the parietotemporal areas of the left hemisphere. It is suggested that thalamic aphasia could result from structural subcortical damage with a homolateral functional cortical deficit leading to the specific aphasic disturbance.

[The alexias]. / Le alessie.

The authors propose a review about Alexias according to the latest theories. Anatomoclinical and linguistic classification of alexia are reported. Some hypotheses about reading processes, according to linguistic classification, are discussed.

[Amyotrophic lateral sclerosis and dementia: a rare association. Case report]. / Sclerosi laterale amiotrofica e demenza: una rara associazione. Osservazione clinica di un caso.

It has been reported a case of a young man with a rare syndrome: amyotrophic lateral sclerosis with dementia. The case is discussed with reference to some pathogenetic ipothesis.

[Choreoathetosis. Uncommon manifestation during chronic liver disease with portocaval shunt]. / Coreoatetosi. Una manifestazione non comune in corso di epatopatie croniche con shunt porto-cavale.

"Acquired hepatocerebral degeneration" is a rare syndrome characterized by extrapiramidal symptomathology in patients affected by liver complaint with porta-cava shunt. Extrapiramidal symptomathology become chronical and progressive and its development is partially independent from the basic liver complaint. We report one case of "acquired hepatocerebral degeneration" whose clinical features lead us to advance a pathogenetic hypothesis on the role played by neurotransmitters in this syndrome.