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      Twenty Years of Subcutaneous Interferon-Beta-1a for Multiple Sclerosis: Contemporary Perspectives

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          Abstract

          Multiple sclerosis (MS) is a chronic, progressive, inflammatory disorder of the central nervous system. Relapsing–remitting MS (RRMS), the most common form of the disease, is characterized by transient neurological dysfunction with concurrent accumulation of disability. Over the past three decades, disease-modifying therapies (DMTs) capable of reducing the frequency of relapses and slowing disability worsening have been studied and approved for use in patients with RRMS. The first DMTs were interferon-betas (IFN-βs), which were approved in the 1990s. Among them was IFN-β-1a for subcutaneous (sc) injection (Rebif ®), which was approved for the treatment of MS in Europe and Canada in 1998 and in the USA in 2002. Twenty years of clinical data and experience have supported the efficacy and safety of IFN-β-1a sc in the treatment of RRMS, including pivotal trials, real-world data, and extension studies lasting up to 15 years past initial treatment. Today, IFN-β-1a sc remains an important therapeutic option in clinical use, especially around pregnancy planning and lactation, and may also be considered for aging patients, in which MS activity declines and long-term immunosuppression associated with some alternative therapies is a concern. In addition, IFN-β-1a sc is used as a comparator in many clinical studies and provides a framework for research into the mechanisms by which MS begins and progresses.

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          Most cited references149

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          Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

          The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
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            Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results

            Abstract Background World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19). Methods We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. Results At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. Conclusions These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)
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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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                Author and article information

                Contributors
                mfreedman@toh.ca
                Journal
                Neurol Ther
                Neurol Ther
                Neurology and Therapy
                Springer Healthcare (Cheshire )
                2193-8253
                2193-6536
                11 January 2024
                11 January 2024
                April 2024
                : 13
                : 2
                : 283-322
                Affiliations
                [1 ]Department of Medicine, University of Ottawa, ( https://ror.org/03c4mmv16) Ottawa, ON K1H 8L6 Canada
                [2 ]The Ottawa Hospital Research Institute, ( https://ror.org/05jtef216) 501 Smyth, Ottawa, ON K1H 8L6 Canada
                [3 ]Department of Neurology, Renaissance School of Medicine, Stony Brook University, ( https://ror.org/05qghxh33) New York, NY 11794 USA
                [4 ]Katholisches Klinikum Bochum, Ruhr University, ( https://ror.org/05k5t2r42) 44787 Bochum, Germany
                [5 ]The MS Center for Innovations in Care, Missouri Baptist Medical Center, ( https://ror.org/0067dx910) 3009 N. Ballas Road, Suite 105B, St. Louis, MO 63131 USA
                [6 ]Neurology MS Center, Consultants in Neurology, Ltd, ( https://ror.org/024f1d020) 1535 Lake Cook Road, Suite 601, Northbrook, IL 60062 USA
                [7 ]Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, ( https://ror.org/01y64my43) Buffalo, NY 14215 USA
                [8 ]Jacobs MS Center for Treatment and Research, Buffalo, NY 14202 USA
                [9 ]Pediatric MS Center, NY State MS Consortium, 1010 Main Street, Buffalo, NY 14203 USA
                [10 ]Division of Neuroimmunology, Department of Neurology, Thomas Jefferson University, ( https://ror.org/00ysqcn41) 900 Walnut St, Rm 305-B, Philadelphia, PA 19107 USA
                [11 ]GRID grid.39009.33, ISNI 0000 0001 0672 7022, Merck Healthcare KGaA, ; 64293 Darmstadt, Germany
                [12 ]GRID grid.481568.6, EMD Serono Research & Development Institute Inc., an affiliate of Merck GKaA, ; Billerica, MA 01821 USA
                [13 ]GRID grid.481568.6, EMD Serono Inc., an affiliate of Merck KGaA, ; Rockland, MA 02370 USA
                [14 ]Department of Neurology A-205, University of Chicago Medicine, ( https://ror.org/024mw5h28) MC-2030, 5841 S Maryland Ave, Chicago, IL 60637 USA
                Article
                565
                10.1007/s40120-023-00565-7
                10951191
                38206453
                f2e607e5-2aff-4789-bcd5-e3b4ae704576
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial 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-nc/4.0/.

                History
                : 26 July 2023
                : 6 November 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004755, EMD Serono;
                Categories
                Review
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                © Springer Healthcare Ltd., part of Springer Nature 2024

                disease-modifying therapies,interferons,interferon-beta-1a,interferon-β-1a for subcutaneous injection,multiple sclerosis,relapsing–remitting multiple sclerosis

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