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      Early and unrestricted access to high-efficacy disease-modifying therapies: a consensus to optimize benefits for people living with multiple sclerosis

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          Abstract

          Early intervention with high-efficacy disease-modifying therapy (HE DMT) may be the best strategy to delay irreversible neurological damage and progression of multiple sclerosis (MS). In European healthcare systems, however, patient access to HE DMTs in MS is often restricted to later stages of the disease due to restrictions in reimbursement despite broader regulatory labels. Although not every patient should be treated with HE DMTs at the initial stages of the disease, early and unrestricted access to HE DMTs with a positive benefit–risk profile and a reasonable value proposition will provide the freedom of choice for an appropriate treatment based on a shared decision between expert physicians and patients. This will further optimize outcomes and facilitate efficient resource allocation and sustainability in healthcare systems and society.

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          The online version contains supplementary material available at 10.1007/s00415-021-10836-8.

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          Most cited references32

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          Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

          B cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells.
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            Global, regional, and national burden of multiple sclerosis 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

            Summary Background Multiple sclerosis is the most common inflammatory neurological disease in young adults. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic method of quantifying various effects of a given condition by demographic variables and geography. In this systematic analysis, we quantified the global burden of multiple sclerosis and its relationship with country development level. Methods We assessed the epidemiology of multiple sclerosis from 1990 to 2016. Epidemiological outcomes for multiple sclerosis were modelled with DisMod-MR version 2.1, a Bayesian meta-regression framework widely used in GBD epidemiological modelling. Assessment of multiple sclerosis as the cause of death was based on 13 110 site-years of vital registration data analysed in the GBD's cause of death ensemble modelling module, which is designed to choose the optimum combination of mathematical models and predictive covariates based on out-of-sample predictive validity testing. Data on prevalence and deaths are summarised in the indicator, disability-adjusted life-years (DALYs), which was calculated as the sum of years of life lost (YLLs) and years of life lived with a disability. We used the Socio-demographic Index, a composite indicator of income per person, years of education, and fertility, to assess relations with development level. Findings In 2016, there were 2 221 188 prevalent cases of multiple sclerosis (95% uncertainty interval [UI] 2 033 866–2 436 858) globally, which corresponded to a 10·4% (9·1 to 11·8) increase in the age-standardised prevalence since 1990. The highest age-standardised multiple sclerosis prevalence estimates per 100 000 population were in high-income North America (164·6, 95% UI, 153·2 to 177·1), western Europe (127·0, 115·4 to 139·6), and Australasia (91·1, 81·5 to 101·7), and the lowest were in eastern sub-Saharan Africa (3·3, 2·9–3·8), central sub-Saharan African (2·8, 2·4 to 3·1), and Oceania (2·0, 1·71 to 2·29). There were 18 932 deaths due to multiple sclerosis (95% UI 16 577 to 21 033) and 1 151 478 DALYs (968 605 to 1 345 776) due to multiple sclerosis in 2016. Globally, age-standardised death rates decreased significantly (change −11·5%, 95% UI −35·4 to −4·7), whereas the change in age-standardised DALYs was not significant (−4·2%, −16·4 to 0·8). YLLs due to premature death were greatest in the sixth decade of life (22·05, 95% UI 19·08 to 25·34). Changes in age-standardised DALYs assessed with the Socio-demographic Index between 1990 and 2016 were variable. Interpretation Multiple sclerosis is not common but is a potentially severe cause of neurological disability throughout adult life. Prevalence has increased substantially in many regions since 1990. These findings will be useful for resource allocation and planning in health services. Many regions worldwide have few or no epidemiological data on multiple sclerosis, and more studies are needed to make more accurate estimates. Funding Bill & Melinda Gates Foundation.
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              Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis.

              Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis. In this 12-month, double-blind, double-dummy study, we randomly assigned 1292 patients with relapsing-remitting multiple sclerosis who had a recent history of at least one relapse to receive either oral fingolimod at a daily dose of either 1.25 or 0.5 mg or intramuscular interferon beta-1a (an established therapy for multiple sclerosis) at a weekly dose of 30 microg. The primary end point was the annualized relapse rate. Key secondary end points were the number of new or enlarged lesions on T(2)-weighted magnetic resonance imaging (MRI) scans at 12 months and progression of disability that was sustained for at least 3 months. A total of 1153 patients (89%) completed the study. The annualized relapse rate was significantly lower in both groups receiving fingolimod--0.20 (95% confidence interval [CI], 0.16 to 0.26) in the 1.25-mg group and 0.16 (95% CI, 0.12 to 0.21) in the 0.5-mg group--than in the interferon group (0.33; 95% CI, 0.26 to 0.42; P<0.001 for both comparisons). MRI findings supported the primary results. No significant differences were seen among the study groups with respect to progression of disability. Two fatal infections occurred in the group that received the 1.25-mg dose of fingolimod: disseminated primary varicella zoster and herpes simplex encephalitis. Other adverse events among patients receiving fingolimod were nonfatal herpesvirus infections, bradycardia and atrioventricular block, hypertension, macular edema, skin cancer, and elevated liver-enzyme levels. This trial showed the superior efficacy of oral fingolimod with respect to relapse rates and MRI outcomes in patients with multiple sclerosis, as compared with intramuscular interferon beta-1a. Longer studies are needed to assess the safety and efficacy of treatment beyond 1 year. (ClinicalTrials.gov number, NCT00340834.) 2010 Massachusetts Medical Society
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                Author and article information

                Contributors
                filippi.massimo@hsr.it
                Journal
                J Neurol
                J Neurol
                Journal of Neurology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-5354
                1432-1459
                9 October 2021
                9 October 2021
                : 1-8
                Affiliations
                [1 ]GRID grid.18887.3e, ISNI 0000000417581884, Neurology Unit, Neurorehabilitation Unit, Neurophysiology Service, and Neuroimaging Research Unit, Division of Neuroscience, , IRCCS San Raffaele Scientific Institute, ; Via Olgettina, 60, 20132 Milan, Italy
                [2 ]GRID grid.15496.3f, Vita-Salute San Raffaele University, ; Milan, Italy
                [3 ]GRID grid.5395.a, ISNI 0000 0004 1757 3729, University of Pisa, ; Pisa, Italy
                [4 ]GRID grid.6612.3, ISNI 0000 0004 1937 0642, University of Basel, ; Basel, Switzerland
                [5 ]GRID grid.420004.2, ISNI 0000 0004 0444 2244, The Newcastle Upon Tyne Hospitals, ; Newcastle upon Tyne, UK
                [6 ]GRID grid.5608.b, ISNI 0000 0004 1757 3470, University of Padua, ; Padua, Italy
                [7 ]GRID grid.5570.7, ISNI 0000 0004 0490 981X, Ruhr-Universität Bochum, ; Bochum, Germany
                [8 ]GRID grid.4491.8, ISNI 0000 0004 1937 116X, Department of Neurology, First Medical Faculty, , Charles University, ; Prague, Czech Republic
                [9 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Medical University Vienna, ; Vienna, Austria
                [10 ]GRID grid.4691.a, ISNI 0000 0001 0790 385X, Università Degli Studi Di Napoli ‘Federico II’, ; Naples, Italy
                [11 ]GRID grid.411083.f, ISNI 0000 0001 0675 8654, MS Centre of Catalonia at the Hospital Vall d’Hebron, ; Barcelona, Spain
                [12 ]GRID grid.415431.6, ISNI 0000 0000 9124 9231, Klinikum Klagenfurt,, ; Klagenfurt am Wörthersee, Austria
                [13 ]GRID grid.7644.1, ISNI 0000 0001 0120 3326, University of Bari, ; Bari, Italy
                Author information
                http://orcid.org/0000-0002-5485-0479
                Article
                10836
                10.1007/s00415-021-10836-8
                8501364
                34626224
                cb80ac32-e26e-449d-9d97-506a037882de
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 August 2021
                : 29 September 2021
                : 29 September 2021
                Categories
                Short Commentary

                Neurology
                benefit–risk profile,unrestricted access,healthcare system,high-efficacy disease-modifying therapy,multiple sclerosis,pharmacoeconomics

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