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.

Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register.

BACKGROUND: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. METHODS: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000-2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers' characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. RESULTS: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. DISCUSSION: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers' characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.

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.

Why physicians need to look more closely at the use of complementary and alternative medicine by multiple sclerosis patients.

With the aim of contributing to the knowledge of attitudes, patterns and motivations for the use of complementary and alternative medicine (CAM) for multiple sclerosis (MS), 109 MS outpatients, or their close relative in cases of mental status impairment, were interviewed using a semi-structured questionnaire. The main results are: (i). 35.7% used at least one CAM at least once; (ii). homeopathy and diets were the most common; (iii). 39.4% showed a positive attitude towards CAM; (iv). a perceived benefit was recorded in 61.5% of cases; (v). the referral source was a physician in only 12.8% of cases; (vi). caring neurologist was not consulted in 82% and generalist was not consulted in 67% of cases; (vii). of 61 CAM interventions, 21 were expected to be disease-modifying and 40 symptomatic; (viii). CAM negatively influenced compliance with conventional medical management in very few cases (2/39); (ix). a higher expanded disability status scale (EDSS) was observed in CAM users; and (x). in those who used CAM during last 3 years (21.1%), the approximate mean cost per year per person was 483 euro. In Italy, the use of CAM in MS is widespread but costly. This study has provided further baseline data on which to assess trends in CAM use and has highlighted issues for patients and conventional doctors about the use of CAM to deal with health problems. More research into the implications of concurrent use of CAM with conventional medicine on public health care is required.

General practitioners facing dementia: are they fully prepared?

We assessed knowledge about Alzheimer's disease (AD) in a sample of Italian general practitioners (GPs). We first carried out a propedeutic study to verify the ability of an Italian version of the University of Alabama at Birmingham's AD Knowledge Test for Health Professionals to distinguish between 20 AD specialists and 20 non-specialists and to gain reference values. We then administered the test, together with a short questionnaire, to 139 GPs attending an educational programme in November 2000. The cut-off score for discriminating specialists from non-specialists was >/=9. Among the 95 GPs who performed the AD Knowledge Test (68.3% response rate), 21% had a total score >/=9. Our findings suggest that particular focus should be given to dementia in continuing medical education (CME) programmes for GPs.

Absence of HHV-6 and HHV-7 in cerebrospinal fluid in relapsing-remitting multiple sclerosis.

OBJECTIVE: To contribute to clarifying the controversy on the association between Human Herpesviruses 6 and 7 (HHV-6, HHV-7) and multiple sclerosis (MS) studying patients with relapsing-remitting MS (RRMS) with or without evidence of disease activity (clinically or radiologically evaluated). MATERIAL AND METHODS: In 25 RRMS patients, 7 suspected MS patients and 9 patients with other neurological diseases, the following parameters were analysed: i) antibody titers (IgM and IgG) against HHV-6 by indirect immunofluorescence both in serum and cerebrospinal fluid (CSF) samples; ii) PCR-detection of HHV-6 DNA and HHV-7 DNA in CSF and HHV-6 DNA in peripheral blood mononuclear cells (PBMCs). MS patients in remission underwent a gadolinium-enhanced magnetic resonance imaging in proximity of sample collections. RESULTS: No viral DNA was found in any CSF sample, HHV-6 DNA frequency in PBMCs of MS patients and controls was not statistically different. Antibody titers against HHV-6 were comparable to those of the general population. Some 30.4% of MS patients were seronegative to HHV6. CONCLUSION: Our data suggest that there is no relationship between HHV-6 or HHV-7 and MS.