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  1. Article: Interferons and natalizumab for multiple sclerosis.

    Clar, Christine / Velasco Garrido, Marcial / Gericke, Christian / Busse, Reinhard

    GMS health technology assessment

    2008  Volume 4, Page(s) Doc09

    Abstract: ... and costs of beta-interferons and natalizumab in the treatment of multiple sclerosis.The review ... cost-effectiveness analyses for interferons were included, whereas no economic evaluations for natalizumab were identified.Use ... with relapsing remitting (and partially with secondary progressive) MS, treatment with natalizumab led ...

    Abstract Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system which is accompanied by considerable disability and high costs. This report summarises the evidence on effectiveness and costs of beta-interferons and natalizumab in the treatment of multiple sclerosis.The review included systematic reviews and randomised controlled trials (with an observation time of at least one year) in patients with MS which assessed outcome parameters such as progression, exacerbations and adverse effects. An extensive literature search included databases such as MEDLINE, EMBASE, the Cochrane Library and various HTA-databases. Studies were selected according to predefined criteria, their quality was assessed according to criteria defined prospectively, and data were summarised systematically in tables. Cost-effectiveness evaluations were also included.Two systematic reviews and 24 randomised controlled trials of beta-interferon therapy were included, as well as three trials on the effectiveness of natalizumab. A total of 22 cost-effectiveness analyses for interferons were included, whereas no economic evaluations for natalizumab were identified.Use of interferon beta-1a or interferon beta-1b after a first demyelinating event led to a reduction of the conversion to definite MS during an observation time of two to three years. In relapsing remitting MS, interferon beta-1a reduced progression. The effects of interferon beta-1b on progression are unclear. Interferon beta-1a and interferon beta-1b reduced in some but not all studies outcomes relating to exacerbations. In direct comparison trials, interferon beta-1b (Betaferon(®) or Betaseron(®)) and interferon beta-1a (Rebif(®), higher dosage of 44 µg three subcutaneous injections per week) proved superior to interferon beta-1a (Avonex(®), 30 µg per week intramuscular) with respect to exacerbation outcomes. For secondary progressive MS, only one of five studies found a reduced progression with interferon beta-1a and only a part of the studies found an improvement with respect to outcomes relating to exacerbations. For primary progressive MS no advantage of therapy with beta-interferons was found with respect to patient-related outcomes. Beta-interferons showed characteristic and frequently occurring adverse effects, including reactions at the injection site and flu-like symptoms. A large proportion of patients stop interferon therapy because of adverse events. The other main reason for stopping therapy is the felt ineffectiveness of the treatment when patients experience a new exacerbation while on treatment. Many patients produce interferon-neutralising antibodies during therapy. The ultimate effect of neutralising antibodies on the efficacy of interferon treatment is unclear.In patients with relapsing remitting (and partially with secondary progressive) MS, treatment with natalizumab led to a reduction of progression and of exacerbation rates. However, a number of cases of progressive multifocal leucoencephalopathy have been reported after natalizumab therapy. These raise serious concerns about patient safety. Reliable data on the long term effectiveness of beta-interferons or natalizumab are not yet available.The absolute cost of interferon therapy is high and the available, international cost-effectiveness analyses indicate a high cost for achieving moderate benefits in quality of life. Further research is needed to provide specific cost-effectiveness estimates for Germany.
    Language English
    Publishing date 2008-10-01
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2212439-1
    ISSN 1861-8863
    ISSN 1861-8863
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Interferons and Natalizumab for Multiple Sclerosis

    Busse, Reinhard / Gericke, Christian / Velasco Garrido, Marcial / Clar, Christine

    GMS Health Technology Assessment, Vol 4, p Doc

    2008  Volume 09

    Abstract: ... and costs of beta-interferons and natalizumab in the treatment of multiple sclerosis. The review ... of beta-interferons or natalizumab are not yet available. The absolute cost of interferon therapy is high and ... cost-effectiveness analyses for interferons were included, whereas no economic evaluations for natalizumab were identified ...

    Abstract Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system which is accompanied by considerable disability and high costs. This report summarises the evidence on effectiveness and costs of beta-interferons and natalizumab in the treatment of multiple sclerosis. The review included systematic reviews and randomised controlled trials (with an observation time of at least one year) in patients with MS which assessed outcome parameters such as progression, exacerbations and adverse effects. An extensive literature search included databases such as MEDLINE, EMBASE, the Cochrane Library and various HTA-databases. Studies were selected according to predefined criteria, their quality was assessed according to criteria defined prospectively, and data were summarised systematically in tables. Cost-effectiveness evaluations were also included.Two systematic reviews and 24 randomised controlled trials of beta-interferon therapy were included, as well as three trials on the effectiveness of natalizumab. A total of 22 cost-effectiveness analyses for interferons were included, whereas no economic evaluations for natalizumab were identified. Use of interferon beta-1a or interferon beta-1b after a first demyelinating event led to a reduction of the conversion to definite MS during an observation time of two to three years. In relapsing remitting MS, interferon beta-1a reduced progression. The effects of interferon beta-1b on progression are unclear. Interferon beta-1a and interferon beta-1b reduced in some but not all studies outcomes relating to exacerbations. In direct comparison trials, interferon beta-1b (Betaferon® or Betaseron®) and interferon beta-1a (Rebif®, higher dosage of 44 µg three subcutaneous injections per week) proved superior to interferon beta-1a (Avonex®, 30 µg per week intramuscular) with respect to exacerbation outcomes. For secondary progressive MS, only one of five studies found a reduced progression with interferon beta-1a and only a part of the studies found an improvement with respect to outcomes relating to exacerbations. For primary progressive MS no advantage of therapy with beta-interferons was found with respect to patient-related outcomes. Beta-interferons showed characteristic and frequently occurring adverse effects, including reactions at the injection site and flu-like symptoms. A large proportion of patients stop interferon therapy because of adverse events. The other main reason for stopping therapy is the felt ineffectiveness of the treatment when patients experience a new exacerbation while on treatment. Many patients produce interferon-neutralising antibodies during therapy. The ultimate effect of neutralising antibodies on the efficacy of interferon treatment is unclear. In patients with relapsing remitting (and partially with secondary progressive) MS, treatment with natalizumab led to a reduction of progression and of exacerbation rates. However, a number of cases of progressive multifocal leucoencephalopathy have been reported after natalizumab therapy. These raise serious concerns about patient safety. Reliable data on the long term effectiveness of beta-interferons or natalizumab are not yet available. The absolute cost of interferon therapy is high and the available, international cost-effectiveness analyses indicate a high cost for achieving moderate benefits in quality of life. Further research is needed to provide specific cost-effectiveness estimates for Germany.
    Keywords Public aspects of medicine ; RA1-1270 ; Medicine ; R ; DOAJ:Public Health ; DOAJ:Health Sciences
    Subject code 610
    Publishing date 2008-10-01T00:00:00Z
    Publisher German Medical Science, Düsseldorf
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis: A Collaborative Cohort Analysis.

    Bachelet, Delphine / Hässler, Signe / Mbogning, Cyprien / Link, Jenny / Ryner, Malin / Ramanujam, Ryan / Auer, Michael / Hyldgaard Jensen, Poul Erik / Koch-Henriksen, Nils / Warnke, Clemens / Ingenhoven, Kathleen / Buck, Dorothea / Grummel, Verena / Lawton, Andy / Donnellan, Naoimh / Hincelin-Mery, Agnès / Sikkema, Dan / Pallardy, Marc / Kieseier, Bernd /
    Hemmer, Bernard / Hartung, Hans Peter / Soelberg Sorensen, Per / Deisenhammer, Florian / Dönnes, Pierre / Davidson, Julie / Fogdell-Hahn, Anna / Broët, Philippe

    PloS one

    2016  Volume 11, Issue 11, Page(s) e0162752

    Abstract: ... A subset of 5638 interferon-beta (IFNβ)-treated and 3440 natalizumab-treated patients having data ... in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had ... Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect ...

    Abstract Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFNβ)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFNβ-1a subcutaneous and IFNβ-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFNβ-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9-8.4 and pooled HR = 8.7, 95% CI 6.6-11.4 respectively). Patients older than 50 years at start of IFNβ therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4-2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1-1.6). Interestingly we observed that in Sweden and Germany, patients who started IFNβ in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1-2.4 and HR = 2.4, 95% CI 1.5-3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0-1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0-2.0). We confirmed previously reported differences in immunogenicity of the different types of IFNβ. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers.
    MeSH term(s) Adult ; Aged ; Antibodies/blood ; Antibodies/immunology ; Antibodies, Anti-Idiotypic/blood ; Antibodies, Anti-Idiotypic/immunology ; Cohort Studies ; Databases, Factual ; Europe/epidemiology ; Female ; Humans ; Interferon-beta/adverse effects ; Interferon-beta/immunology ; Interferon-beta/therapeutic use ; Male ; Middle Aged ; Multiple Sclerosis/complications ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/epidemiology ; Multiple Sclerosis/mortality ; Natalizumab/adverse effects ; Natalizumab/immunology ; Natalizumab/therapeutic use ; Patient Outcome Assessment ; Population Surveillance ; Proportional Hazards Models ; Risk Factors
    Chemical Substances Antibodies ; Antibodies, Anti-Idiotypic ; Natalizumab ; Interferon-beta (77238-31-4)
    Language English
    Publishing date 2016-11-02
    Publishing country United States
    Document type Journal Article ; Multicenter Study
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0162752
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in Europe: A descriptive study of test results.

    Link, Jenny / Ramanujam, Ryan / Auer, Michael / Ryner, Malin / Hässler, Signe / Bachelet, Delphine / Mbogning, Cyprien / Warnke, Clemens / Buck, Dorothea / Hyldgaard Jensen, Poul Erik / Sievers, Claudia / Ingenhoven, Kathleen / Fissolo, Nicolas / Lindberg, Raija / Grummel, Verena / Donnellan, Naoimh / Comabella, Manuel / Montalban, Xavier / Kieseier, Bernd /
    Soelberg Sørensen, Per / Hartung, Hans-Peter / Derfuss, Tobias / Lawton, Andy / Sikkema, Dan / Pallardy, Marc / Hemmer, Bernhard / Deisenhammer, Florian / Broët, Philippe / Dönnes, Pierre / Davidson, Julie / Fogdell-Hahn, Anna

    PloS one

    2017  Volume 12, Issue 2, Page(s) e0170395

    Abstract: ... the more than 10 years of ADA monitoring in MS patients treated with interferon beta (IFNβ) and natalizumab ... Extavia s.c. (0.99 and 0.94 years) and natalizumab (0.25 and 0.23 years), which were introduced ... of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during ...

    Abstract Antibodies against biopharmaceuticals (anti-drug antibodies, ADA) have been a well-integrated part of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta (IFNβ) and natalizumab have been pooled and characterized through collaboration within a European consortium. The aim of this study was to report on the clinical practice of ADA testing in Europe, considering the number of ADA tests performed and type of ADA assays used, and to determine the frequency of ADA testing against the different drug preparations in different countries. A common database platform (tranSMART) for querying, analyzing and storing retrospective data of MS cohorts was set up to harmonize the data and compare results of ADA tests between different countries. Retrospective data from six countries (Sweden, Austria, Spain, Switzerland, Germany and Denmark) on 20,695 patients and on 42,555 samples were loaded into tranSMART including data points of age, gender, treatment, samples, and ADA results. The previously observed immunogenic difference among the four IFNβ preparations was confirmed in this large dataset. Decreased usage of the more immunogenic preparations IFNβ-1a subcutaneous (s.c.) and IFNβ-1b s.c. in favor of the least immunogenic preparation IFNβ-1a intramuscular (i.m.) was observed. The median time from treatment start to first ADA test correlated with time to first positive test. Shorter times were observed for IFNβ-1b-Extavia s.c. (0.99 and 0.94 years) and natalizumab (0.25 and 0.23 years), which were introduced on the market when ADA testing was already available, as compared to IFNβ-1a i.m. (1.41 and 2.27 years), IFNβ-1b-Betaferon s.c. (2.51 and 1.96 years) and IFNβ-1a s.c. (2.11 and 2.09 years) which were available years before routine testing began. A higher rate of anti-IFNβ ADA was observed in test samples taken from older patients. Testing for ADA varies between different European countries and is highly dependent on the policy within each country. For drugs where routine monitoring of ADA is not in place, there is a risk that some patients remain on treatment for several years despite ADA positivity. For drugs where a strategy of ADA testing is introduced with the release of the drug, there is a reduced risk of having ADA positive patients and thus of less efficient treatment. This indicates that potential savings in health cost might be achieved by routine analysis of ADA.
    MeSH term(s) Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Antibodies/immunology ; Child ; Child, Preschool ; Europe ; Female ; Humans ; Immunologic Factors/adverse effects ; Immunologic Factors/immunology ; Immunologic Factors/therapeutic use ; Infant ; Infant, Newborn ; Interferon-beta/adverse effects ; Interferon-beta/immunology ; Interferon-beta/therapeutic use ; Male ; Middle Aged ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/immunology ; Natalizumab/adverse effects ; Natalizumab/immunology ; Natalizumab/therapeutic use ; Retrospective Studies ; Sex Factors ; Time Factors ; Young Adult
    Chemical Substances Antibodies ; Immunologic Factors ; Natalizumab ; Interferon-beta (77238-31-4)
    Language English
    Publishing date 2017-02-07
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0170395
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in Europe

    Jenny Link / Ryan Ramanujam / Michael Auer / Malin Ryner / Signe Hässler / Delphine Bachelet / Cyprien Mbogning / Clemens Warnke / Dorothea Buck / Poul Erik Hyldgaard Jensen / Claudia Sievers / Kathleen Ingenhoven / Nicolas Fissolo / Raija Lindberg / Verena Grummel / Naoimh Donnellan / Manuel Comabella / Xavier Montalban / Bernd Kieseier /
    Per Soelberg Sørensen / Hans-Peter Hartung / Tobias Derfuss / Andy Lawton / Dan Sikkema / Marc Pallardy / Bernhard Hemmer / Florian Deisenhammer / Philippe Broët / Pierre Dönnes / Julie Davidson / Anna Fogdell-Hahn / ABIRISK Consortium

    PLoS ONE, Vol 12, Iss 2, p e

    A descriptive study of test results.

    2017  Volume 0170395

    Abstract: ... the more than 10 years of ADA monitoring in MS patients treated with interferon beta (IFNβ) and natalizumab ... Extavia s.c. (0.99 and 0.94 years) and natalizumab (0.25 and 0.23 years), which were introduced ... of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during ...

    Abstract Antibodies against biopharmaceuticals (anti-drug antibodies, ADA) have been a well-integrated part of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta (IFNβ) and natalizumab have been pooled and characterized through collaboration within a European consortium. The aim of this study was to report on the clinical practice of ADA testing in Europe, considering the number of ADA tests performed and type of ADA assays used, and to determine the frequency of ADA testing against the different drug preparations in different countries. A common database platform (tranSMART) for querying, analyzing and storing retrospective data of MS cohorts was set up to harmonize the data and compare results of ADA tests between different countries. Retrospective data from six countries (Sweden, Austria, Spain, Switzerland, Germany and Denmark) on 20,695 patients and on 42,555 samples were loaded into tranSMART including data points of age, gender, treatment, samples, and ADA results. The previously observed immunogenic difference among the four IFNβ preparations was confirmed in this large dataset. Decreased usage of the more immunogenic preparations IFNβ-1a subcutaneous (s.c.) and IFNβ-1b s.c. in favor of the least immunogenic preparation IFNβ-1a intramuscular (i.m.) was observed. The median time from treatment start to first ADA test correlated with time to first positive test. Shorter times were observed for IFNβ-1b-Extavia s.c. (0.99 and 0.94 years) and natalizumab (0.25 and 0.23 years), which were introduced on the market when ADA testing was already available, as compared to IFNβ-1a i.m. (1.41 and 2.27 years), IFNβ-1b-Betaferon s.c. (2.51 and 1.96 years) and IFNβ-1a s.c. (2.11 and 2.09 years) which were available years before routine testing began. A higher rate of anti-IFNβ ADA was observed in test samples taken from older patients. Testing for ADA varies between different European ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis

    Delphine Bachelet / Signe Hässler / Cyprien Mbogning / Jenny Link / Malin Ryner / Ryan Ramanujam / Michael Auer / Poul Erik Hyldgaard Jensen / Nils Koch-Henriksen / Clemens Warnke / Kathleen Ingenhoven / Dorothea Buck / Verena Grummel / Andy Lawton / Naoimh Donnellan / Agnès Hincelin-Mery / Dan Sikkema / Marc Pallardy / Bernd Kieseier /
    Bernard Hemmer / Hans Peter Hartung / Per Soelberg Sorensen / Florian Deisenhammer / Pierre Dönnes / Julie Davidson / Anna Fogdell-Hahn / Philippe Broët / ABIRISK Consortium

    PLoS ONE, Vol 11, Iss 11, p e

    A Collaborative Cohort Analysis.

    2016  Volume 0162752

    Abstract: ... A subset of 5638 interferon-beta (IFNβ)-treated and 3440 natalizumab-treated patients having data ... in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had ... Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect ...

    Abstract Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFNβ)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFNβ-1a subcutaneous and IFNβ-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFNβ-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9-8.4 and pooled HR = 8.7, 95% CI 6.6-11.4 respectively). Patients older than 50 years at start of IFNβ therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4-2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1-1.6). Interestingly we observed that in Sweden and Germany, patients who started IFNβ in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1-2.4 and HR = 2.4, 95% CI 1.5-3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0-1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0-2.0). We confirmed previously reported differences in immunogenicity of the different types of IFNβ. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616 ; 610
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Disease-modifying therapies and cost-of-illness progression among people newly diagnosed with multiple sclerosis: a national register-based cohort study covering treatment initiation with interferons, glatiramer acetate or natalizumab.

    Karampampa, Korinna / Gyllensten, Hanna / Friberg, Emilie / Murley, Chantelle / Kavaliunas, Andrius / Hillert, Jan / Olsson, Tomas / Alexanderson, Kristina

    BMJ open

    2023  Volume 13, Issue 5, Page(s) e067516

    Abstract: Objectives: Disease-modifying therapies (DMTs) can slow disease progression in multiple sclerosis ... diagnosed in 2006-2015, when aged 20-55, receiving first-line therapy with interferons (IFN), glatiramer ... diagnosed people with MS in relation to the first DMT received.: Design and setting: A cohort study using ...

    Abstract Objectives: Disease-modifying therapies (DMTs) can slow disease progression in multiple sclerosis (MS). The objective of this study was to explore the cost-of-illness (COI) progression among newly diagnosed people with MS in relation to the first DMT received.
    Design and setting: A cohort study using data from nationwide registers in Sweden.
    Participants: People with MS (PwMS) in Sweden first diagnosed in 2006-2015, when aged 20-55, receiving first-line therapy with interferons (IFN), glatiramer acetate (GA) or natalizumab (NAT). They were followed up through 2016.
    Outcome measures: Outcomes (in Euros, €) were: (1) secondary healthcare costs: specialised outpatient and inpatient care including out-of-pocket expenditure, DMTs including hospital-administered MS therapies, and prescribed drugs, and (2) productivity losses: sickness absence and disability pension. Descriptive statistics and Poisson regression were computed, adjusting for disability progression using the Expanded Disability Status Scale.
    Results: 3673 newly diagnosed PwMS who were treated with IFN (N=2696), GA (N=441) or NAT (N=536) were identified. Healthcare costs were similar for the INF and GA groups, while the NAT group had higher costs (p value<0.05), owing to DMT and outpatient costs. IFN had lower productivity losses than NAT and GA (p value>0.05), driven by fewer sickness absence days. NAT had a trend towards lower disability pension costs compared with GA (p value>0.05).
    Conclusions: Similar trends over time for healthcare costs and productivity losses were identified across the DMT subgroups. PwMS on NAT maintained their work capacity for a longer time compared with those on GA, potentially leading to lower disability pension costs over time. COI serves as an objective measure to explore the importance of DMTs in maintaining low levels of progression of MS over time.
    MeSH term(s) Humans ; Glatiramer Acetate/therapeutic use ; Multiple Sclerosis/drug therapy ; Natalizumab/therapeutic use ; Interferons/therapeutic use ; Interferon-beta/therapeutic use ; Cohort Studies ; Multiple Sclerosis, Relapsing-Remitting/drug therapy ; Cost of Illness ; Immunosuppressive Agents/therapeutic use
    Chemical Substances Glatiramer Acetate (5M691HL4BO) ; Natalizumab ; Interferons (9008-11-1) ; Interferon-beta (77238-31-4) ; Immunosuppressive Agents
    Language English
    Publishing date 2023-05-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2022-067516
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The Effect of Interferon Beta and Natalizumab on miR-20b Expression in Patients with Relapsing-Remitting Multiple Sclerosis is Potentially Mediated by Modulation of the Jak-STAT Signaling Pathway: A Case-control Study.

    Jafari Harandi, Aysan / Mirzaee Sedigh, Alireza / Ataei, Mitra / Bayrami, Sepideh / Esmaeilzadeh, Emran / Sanati, Mohammad Hossein

    Iranian journal of immunology : IJI

    2024  Volume 21, Issue 2

    Abstract: Background: The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ ... in multiple sclerosis (MS) patients have not yet been fully understood. Over the past decades, many studies have been ... RRMS) and 30 healthy controls (HCs) were enrolled. The patients were categorized as untreated (N=20 ...

    Abstract Background: The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ) in multiple sclerosis (MS) patients have not yet been fully understood. Over the past decades, many studies have been conducted to evaluate gene expression changes especially regulatory non-coding RNAs such as microRNAs (miRNAs) following therapy in MS patients.
    Objective: To assess the changes in the expression of miR-20b in MS patients treated with IFN-β or NTZ.
    Methods: Sixty patients with relapsing-remitting MS (RRMS) and 30 healthy controls (HCs) were enrolled. The patients were categorized as untreated (N=20), IFN-β-treated (N=20), and NTZtreated (N=20). For the expression analysis, real-time PCR was performed on the whole blood. The bioinformatic tools were applied for signaling pathways enrichment analysis of miR-20b targetome.
    Results: The relative expression of miR-20b was significantly downregulated in the untreated patients compared with the HCs (-1.726-fold, p<0.001), while IFN-β-treated and NTZ-treated patients showed no statistical difference compared with the HCs (0.733-fold, p=0.99 for IFN-β and 1.025-fold, p=0.18 for NTZ). This indicates the restoration of miR-20b expression to normal level in the treated patients. Additionally, in silico analysis demonstrated that the Jak-STAT signaling pathway is enriched with miR-20b targets (p<0.0001).
    Conclusion: Our findings suggest that the positive effects of IFN-β and NTZ in the RRMS patients could be potentially mediated by returning miR-20b expression to baseline.
    Language English
    Publishing date 2024-05-18
    Publishing country Iran
    Document type Journal Article
    ZDB-ID 2616647-1
    ISSN 1735-367X ; 1735-367X
    ISSN (online) 1735-367X
    ISSN 1735-367X
    DOI 10.22034/iji.2024.100500.2694
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Serum IgG levels to Epstein-Barr and measles viruses in patients with multiple sclerosis during natalizumab and interferon beta treatment.

    Persson Berg, Linn / Eriksson, Marcus / Longhi, Sonia / Kockum, Ingrid / Warnke, Clemens / Thomsson, Elisabeth / Bäckström, Malin / Olsson, Tomas / Fogdell-Hahn, Anna / Bergström, Tomas

    BMJ neurology open

    2022  Volume 4, Issue 2, Page(s) e000271

    Abstract: Background: Patients with multiple sclerosis (MS) demonstrate higher seroprevalence ... of Epstein-Barr virus (EBV) and increased anti-EBV IgG levels in serum compared with healthy controls. Intrathecal ... To measure serum IgG reactivity to EBV glycoprotein 350 (gp350) and MeV nucleocapsid protein (N: Methods ...

    Abstract Background: Patients with multiple sclerosis (MS) demonstrate higher seroprevalence of Epstein-Barr virus (EBV) and increased anti-EBV IgG levels in serum compared with healthy controls. Intrathecal antibody production to measles virus (MeV) is a common finding in patients with MS.
    Objective: To measure serum IgG reactivity to EBV glycoprotein 350 (gp350) and MeV nucleocapsid protein (N
    Methods: Patients with MS (n=728) were included from the Swedish pharmacovigilance study for NAT. Paired serum samples from 714 patients drawn before and during NAT treatment and paired samples from 170 patients during prior IFNβ treatment were analysed. In total, 156 patients were included in both groups. Samples from 144 matched blood donors served as controls. Indirect ELISA was applied using recombinant EBVgp350 and MeV N
    Results: Patients with MS showed higher serum levels of anti-EBVgp350 and anti-MeV N
    Conclusions: Treatment with NAT, which is considered a selective immunosuppressive agent with a compartmentalised effect on the central nervous system, appeared to be associated with a moderate decrease in circulating IgG levels to EBVgp350 and MeV N
    Language English
    Publishing date 2022-07-27
    Publishing country England
    Document type Journal Article
    ISSN 2632-6140
    ISSN (online) 2632-6140
    DOI 10.1136/bmjno-2022-000271
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Cladribine versus fingolimod, natalizumab and interferon β for multiple sclerosis.

    Kalincik, Tomas / Jokubaitis, Vilija / Spelman, Tim / Horakova, Dana / Havrdova, Eva / Trojano, Maria / Lechner-Scott, Jeannette / Lugaresi, Alessandra / Prat, Alexandre / Girard, Marc / Duquette, Pierre / Grammond, Pierre / Solaro, Claudio / Grand'Maison, Francois / Hupperts, Raymond / Prevost, Julie / Sola, Patrizia / Ferraro, Diana / Terzi, Murat /
    Butler, Ernest / Slee, Mark / Kermode, Allan / Fabis-Pedrini, Marzena / McCombe, Pamela / Barnett, Michael / Shaw, Cameron / Hodgkinson, Suzanne / Butzkueven, Helmut

    Multiple sclerosis (Houndmills, Basingstoke, England)

    2017  Volume 24, Issue 12, Page(s) 1617–1626

    Abstract: ... onset multiple sclerosis, exposure to the study therapies and ⩾1-year on-treatment follow-up from MSBase ... lower than on interferon ( p = 0.05), similar to fingolimod ( p = 0.31) and higher than on natalizumab ... fingolimod) and 1410 patients (natalizumab). The probability of experiencing a relapse on cladribine was ...

    Abstract Objective: This propensity score-matched analysis from MSBase compared the effectiveness of cladribine with interferon β, fingolimod or natalizumab.
    Methods: We identified all patients with relapse-onset multiple sclerosis, exposure to the study therapies and ⩾1-year on-treatment follow-up from MSBase. Three pairwise propensity score-matched analyses compared treatment outcomes over 1 year. The outcomes were hazards of first relapse, disability accumulation and disability improvement events. Sensitivity analyses were completed.
    Results: The cohorts consisted of 37 (cladribine), 1940 (interferon), 1892 (fingolimod) and 1410 patients (natalizumab). The probability of experiencing a relapse on cladribine was lower than on interferon ( p = 0.05), similar to fingolimod ( p = 0.31) and higher than on natalizumab ( p = 0.042). The probability of disability accumulation on cladribine was similar to interferon ( p = 0.37) and fingolimod ( p = 0.089) but greater than natalizumab ( p = 0.021). The probability of disability improvement was higher on cladribine than interferon ( p = 0.00017), fingolimod ( p = 0.0025) or natalizumab ( p = 0.00099). Sensitivity analyses largely confirmed the above results.
    Conclusion: Cladribine is an effective therapy for relapse-onset multiple sclerosis. Its effect on relapses is comparable to fingolimod and its effect on disability accrual is comparable to interferon β and fingolimod. Cladribine may potentially associate with superior recovery from disability relative to interferon, fingolimod and natalizumab.
    MeSH term(s) Adult ; Cladribine/therapeutic use ; Cohort Studies ; Female ; Fingolimod Hydrochloride/therapeutic use ; Humans ; Immunosuppressive Agents/therapeutic use ; Interferon-beta/therapeutic use ; Male ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/drug therapy ; Natalizumab/therapeutic use ; Propensity Score ; Recurrence ; Treatment Outcome
    Chemical Substances Immunosuppressive Agents ; Natalizumab ; Cladribine (47M74X9YT5) ; Interferon-beta (77238-31-4) ; Fingolimod Hydrochloride (G926EC510T)
    Language English
    Publishing date 2017-08-31
    Publishing country England
    Document type Comparative Study ; Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 1290669-4
    ISSN 1477-0970 ; 1352-4585
    ISSN (online) 1477-0970
    ISSN 1352-4585
    DOI 10.1177/1352458517728812
    Database MEDical Literature Analysis and Retrieval System OnLINE

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