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      The changing multiple sclerosis treatment landscape: impact of new drugs and treatment recommendations

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          Abstract

          Purpose

          The purpose of this study is to describe the utilization of disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (MS) and assess the impact of both the introduction of new drugs and treatment recommendations (local recommendation on rituximab use issued at the largest MS clinic in Stockholm and regional Drug and Therapeutics Committee (DTC) recommendation on how dimethyl fumarate should be used).

          Methods

          Interrupted time series analyses using monthly data on all MS patients treated with DMTs in the Stockholm County, Sweden, from January 2011 to December 2017.

          Results

          There were 4765 individuals diagnosed with MS residing in the Stockholm County from 2011 to 2017. Of these, 2934 (62%) were treated with an MS DMT. Since 2011, fingolimod, alemtuzumab, teriflunomide, dimethyl fumarate, peginterferon beta-1a, and daclizumab were introduced. Only fingolimod and dimethyl fumarate significantly impacted MS DMT utilization. In parallel, the use of rituximab off-label increased steadily, reaching 58% of all DMT-treated MS patients by the end of the study period. The local recommendation on rituximab was associated with an increase in rituximab use. The regional DTC recommendation on dimethyl fumarate was associated with a decrease in dimethyl fumarate use.

          Conclusions

          Three MS DMTs—fingolimod, dimethyl fumarate, and rituximab off-label—impacted MS DMT utilization in the Stockholm County. The associations between the treatment recommendations and the subsequent changes in MS DMT utilization indicate that such interventions can influence the uptake and utilization of new drugs used in the specialized care setting.

          Electronic supplementary material

          The online version of this article (10.1007/s00228-018-2429-1) contains supplementary material, which is available to authorized users.

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          Most cited references12

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          Rituximab versus fingolimod after natalizumab in multiple sclerosis patients.

          Many JC virus antibody-positive relapsing-remitting multiple sclerosis (RRMS) patients who are stable on natalizumab switch to other therapies to avoid progressive multifocal leukoencephalopathy.
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            Testing for serial correlation in least squares regression. II.

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              Factors affecting the uptake of new medicines: a systematic literature review

              Background The successful diffusion of new drugs is crucial for both pharmaceutical companies and patients—and of wider stakeholder concern, including for the funding of healthcare provision. Micro-level characteristics (the socio-demographic and professional characteristics of medical professionals), meso-level characteristics (the prescribing characteristics of doctors, the marketing efforts of pharmaceutical companies, interpersonal communication among doctors, drug attributes, and the characteristics of patients), and macro-level characteristics (government policies) all influence the diffusion of new drugs. This systematic literature review examines the micro- and meso-level characteristics of early prescribers of newly introduced drugs. Understanding the characteristics of early adopters may help to speed up the diffusion process, promote cost-efficient prescribing habits, forecast utilisation, and develop targeted intervention strategies. Methods The PubMed and Scopus electronic databases were chosen for their extensive coverage of the pertinent literature and used to identify 205 potentially relevant studies by means of a four-layered search string. The 35 studies deemed eligible were then synthetized carefully and critically, to extract variables relevant to this review. Results Early adoption of new drugs is not a personal trait, independent of drug type, but early adopters share both micro- and meso-level characteristics. At prescriber level, doctors’ interest in particular therapeutic areas, participation in clinical trials, and volume of prescribing—either in total or within the therapeutic class of the new drug—increase the likelihood of early adoption. The marketing efforts of pharmaceutical companies and doctors’ professional and social interactions leading to prescribing contagion are very powerful predictors of new drug uptake. At patient level, doctors with younger patients, patients with higher socioeconomic statuses and/or patients with poorer health statuses are more inclined to prescribe new drugs early. In contrast, the socio-demographic characteristics of prescribers and many practice-related factors play little role in the adoption process. Conclusions The most powerful predictors of new drug uptake include the doctors’ strong scientific commitment, high prescribing volume in total or in within the therapeutic class of the new drug, high exposure to marketing, and intense communication with colleagues.
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                Author and article information

                Contributors
                irene.eriksson@ki.se
                Journal
                Eur J Clin Pharmacol
                Eur. J. Clin. Pharmacol
                European Journal of Clinical Pharmacology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0031-6970
                1432-1041
                10 February 2018
                10 February 2018
                2018
                : 74
                : 5
                : 663-670
                Affiliations
                [1 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Medicine Solna, , Karolinska Institutet, ; Stockholm, Sweden
                [2 ]ISNI 0000 0001 2326 2191, GRID grid.425979.4, Department of Healthcare Development, Stockholm County Council, ; Stockholm, Sweden
                [3 ]ISNI 0000000120346234, GRID grid.5477.1, Department of Pharmaceutical Sciences, , Utrecht University, ; Utrecht, the Netherlands
                [4 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Clinical Neuroscience, , Karolinska Institutet, ; Stockholm, Sweden
                [5 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, Clinical Pharmacology, , Karolinska University Hospital, ; Stockholm, Sweden
                [6 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Clinical Science and Education, Södersjukhuset, , Karolinska Institutet, ; Stockholm, Sweden
                Author information
                http://orcid.org/0000-0002-3760-6423
                Article
                2429
                10.1007/s00228-018-2429-1
                5893684
                29429031
                9091d542-5e97-4883-8176-fc034a2d3850
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 15 November 2017
                : 1 February 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004348, Stockholms Läns Landsting;
                Categories
                Pharmacoepidemiology and Prescription
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2018

                Pharmacology & Pharmaceutical medicine
                rituximab,dimethyl fumarate,drug and therapeutics committee,drug utilization,multiple sclerosis, relapsing-remitting

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