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      Real‐life long‐term effectiveness of fingolimod in Swiss patients with relapsing‐remitting multiple sclerosis

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          Abstract

          Background and purpose

          In 2011, fingolimod was approved in Switzerland for the treatment of relapsing‐remitting multiple sclerosis (RRMS). The aim of the present study was to assess the effectiveness and retention of fingolimod in a real‐life Swiss setting, in which patients can receive fingolimod as both first‐ and second‐line treatment for RRMS.

          Methods

          This cross‐sectional, observational study with retrospective data collection was performed at 19 sites that comprised both hospitals and office‐based physicians across Switzerland. Sites were asked to document eligible patients in consecutive chronological order to avoid selection bias. Demographic and clinical data from 274 consenting adult patients with RRMS who had received treatment with fingolimod were analyzed.

          Results

          Mean treatment duration with fingolimod was 32 months. Under fingolimod, 77.7% of patients remained free from relapses and 90.3% did not experience disability progression. The proportion of patients who were free from any clinical disease activity, i.e. without relapses and disability progression, was 72.1%. A total of 28.5% of patients had been RRMS treatment‐naïve prior to fingolimod therapy. High long‐term treatment retention rates ranging between 95.7% at 24 months and 87.8% at 36 months were observed.

          Conclusion

          In this Swiss cohort of naïve and pre‐treated subjects with RRMS, the majority of patients under fingolimod treatment showed freedom from relapses and disability progression. In addition, treatment retention rate over 2 and 3 years was high, irrespective of previous treatment.

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          Most cited references13

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          Optimizing the benefit of multiple sclerosis therapy: the importance of treatment adherence

          Poor treatment adherence is problematic in many therapy areas, including multiple sclerosis (MS). Several immunomodulatory drugs are available for the treatment of MS, all of which require frequent parenteral administration. Current first-line therapies are two formulations of interferon (IFN) beta-1a, one of IFN beta-1b, and one of glatiramer acetate. Discontinuation of treatment is common, particularly in the first few months after initiation. Although the true effect of poor adherence to MS therapy is not known, it is likely to lead to a fall in treatment efficacy. Many factors influence a patient’s adherence to treatment, including the patient’s MS subtype and disability level, cognitive impairment resulting from MS, perceived lack of efficacy of the prescribed medication, and adverse events associated with MS therapy. This article summarizes the barriers to adherence to MS therapies, and discusses patient management strategies that can be employed to encourage adherence. Future advances in the field of MS treatment will be explored, including the development of orally administered drugs, which may enhance adherence.
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            Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients.

            A number of studies have reported flare-up of multiple sclerosis (MS) disease activity after cessation of natalizumab, increasing to a level beyond the pre-natalizumab treatment level. Our aim was to describe the development in clinical disease activity following cessation of natalizumab therapy in a large unselected cohort of highly active patients. We studied 375 highly active patients who had suffered at least two significant relapses within 1 year or three relapses within 2 years, or had been treated with mitoxantrone for highly active disease. All patients had discontinued therapy with natalizumab after at least 24 weeks on therapy, and had been followed 3-12 months (mean 8.9 months) after cessation of natalizumab therapy. The annualised relapse rate before start of natalizumab therapy was 0.94 (95 % confidence interval [CI] 0.88-1.00), 0.47 (95 % CI 0.43-0.52) during natalizumab therapy, 0.63 (95 % CI 0.51-0.76) 1-6 months after natalizumab and 0.55 (95 % CI 0.42-0.70) 7-12 months after natalizumab. However, 83 (22 %) of the patients could be classified as showing rebound of relapses, defined as a higher individual relapse rate after cessation of natalizumab than before natalizumab. These patients had a higher annualised relapse rate during natalizumab therapy. For the whole patient group, the relapse rate after discontinuation did not exceed the pre-natalizumab relapse rate at any time, but 22 % of the patients showed rebound of relapses after discontinuation of natalizumab.
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              Demyelinating events in early multiple sclerosis have inherent severity and recovery.

              It is unclear whether the severity of and recovery from the initial demyelinating event (IDE) are recapitulated in subsequent multiple sclerosis (MS) relapses. We sought to identify the factors associated with relapse severity and recovery and to evaluate whether events have inherent severity or recovery. Patients seen at the UCSF MS Clinic within 1 year of disease onset were identified from a prospective database. Ordinal logistic regression was used to analyze predictors of three-level categorizations of event severity and recovery. We identified 330 patients with MS or clinically isolated syndrome; 152 had a second event and 63 had a third event. Nonwhite and younger patients were at an increased risk of more severe demyelinating events. A severe prior event predicted a substantial increase in the odds of being above any given severity cutoff for a severe subsequent event (for second event severity, odds ratio [OR] = 5.62, 95% confidence interval [CI] [2.39, 13.26], p < 0.0001; for third event severity, OR = 6.74, 95% CI [1.67, 27.18], p = 0.007). Similarly, poor recovery of the IDE predicted poor second event recovery (OR = 5.28, 95% CI [1.95, 14.25], p = 0.001), while fair or poor second event recovery predicted about a 5- or 13-fold increase in the odds of poor third event recovery. A more severe event also predicted a substantial increase in the odds of poor recovery. Patients with severe presentation and poor recovery at disease onset continue on a similar trajectory with subsequent demyelinating events. Whether genetic or other biologic factors are responsible for this pattern remains to be determined.
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                Author and article information

                Contributors
                Chiara.Zecca@eoc.ch
                Journal
                Eur J Neurol
                Eur. J. Neurol
                10.1111/(ISSN)1468-1331
                ENE
                European Journal of Neurology
                John Wiley and Sons Inc. (Hoboken )
                1351-5101
                1468-1331
                06 March 2018
                May 2018
                : 25
                : 5 ( doiID: 10.1111/ene.2018.25.issue-5 )
                : 762-767
                Affiliations
                [ 1 ] Department of Neurology Neurocenter of Southern Switzerland Regional Hospital Lugano (EOC) Lugano
                [ 2 ] Neurology Practice Carouge Geneva
                [ 3 ] Department of Neurology Cantonal Hospital Aarau Aarau
                [ 4 ] Novartis Pharma Schweiz AG Rotkreuz
                [ 5 ] Department of Ophthalmology Hospital of the Canton of Luzern Luzern
                [ 6 ] Neurozentrum Oberaargau Langenthal
                [ 7 ] Department of Neurology Inselspital Bern University Hospital and University of Bern Bern
                [ 8 ] Division of Neurology Department of Neurosciences Faculty of Medicine University Hospital of Geneva Geneva
                [ 9 ] Neurozentrum Bellevue Zürich and Department of Neurology University of Basel Basel Switzerland
                Author notes
                [*] [* ]Correspondence: C. Zecca, Centro Sclerosi Multipla, Neurocentro della Svizzera Italiana, via Tesserete 46, 6903 Lugano, Switzerland (tel.: +41 (0)91 811 6604; fax: +41 (0)91 811 6915; e‐mail: Chiara.Zecca@ 123456eoc.ch ).
                Article
                ENE13594
                10.1111/ene.13594
                5969089
                29431876
                8c5a45a3-8499-47f8-8235-8a03f0657578
                © 2018 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 18 December 2017
                : 06 February 2018
                Page count
                Figures: 4, Tables: 2, Pages: 6, Words: 4243
                Funding
                Funded by: Novartis Pharma AG
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                ene13594
                May 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.8.2 mode:remove_FC converted:25.05.2018

                Neurology
                fingolimod,long‐term effectiveness,multiple sclerosis,real life,real world,retention,switzerland

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