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Xavier Montalban - One of the best experts on this subject based on the ideXlab platform.

  • The 11-year long-term follow-up study from the randomized BENEFIT CIS trial
    Neurology, 2016
    Co-Authors: Ludwig Kappos, Hanspeter Hartung, Frederik Barkhof, G Edan, Xavier Montalban, Bernhard Hemmer, Sven Schippling, Mark Freedman, Edward Fox, Andrea Schulze
    Abstract:

    Objective: To assess outcomes for patients treated with Interferon Beta-1b immediately after clinically isolated syndrome (CIS) or after a short delay. Methods: Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment) were randomly assigned to receive Interferon Beta-1b (early treatment) or placebo (delayed treatment). After conversion to clinically definite multiple sclerosis (CDMS) or 2 years, patients on placebo could switch to Interferon Beta-1b or another treatment. Eleven years after randomization, patients were reassessed. Results: Two hundred seventy-eight (59.4%) of the original 468 patients (71.3% of those eligible at participating sites) were enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm (p 5 0.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888 [540, not reached] vs 931 [253, 3,296]; p50.0005) and lower overall annualized relapse rate (0.21 vs 0.26; p50.0018). Only 25 patients (5.9%, overall; early, 4.5%; delayed, 8.3%) converted to secondary progressive multiple sclerosis. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms (median [Q1,Q3]: 2.0 [1.0, 3.0]). The early-treatment group had better Paced Auditory Serial Addition Task–3 total scores (p 5 0.0070). Employment rates remained high, and health resource utilization tended to be low in both groups.MRI metrics did not differ between groups. Conclusions: Although the delay in treatment was relatively short, several clinical outcomes favored earlier treatment. Along with low rates of disability and disease progression in both groups, this supports the value of treatment at CIS.

  • baseline predictors of disease activity in patients with cis treated with Interferon Beta 1b in the benefit 11 trial p2 121
    Neurology, 2016
    Co-Authors: M S Freedman, Ludwig Kappos, Frederik Barkhof, G Edan, Xavier Montalban, Hans Hartung, Bernhard Hemmer, Edward J Fox, Sven Schippling, R Koelbach
    Abstract:

    Objective: To analyze baseline patient characteristics for prediction of disease outcomes 11 years postrandomization. Background: A number of variables have been identified that are assessable early in the course of MS that may predict the disease course. Long-term follow up from the BENEFIT trial, which enrolled patients with clinically-isolated syndrome, is a unique opportunity to assess the predictive capacity of these variables. Methods: Patients were randomized to initial treatment with Interferon Beta-1b or placebo for 2 years or until diagnosis of clinically-definite multiple sclerosis (CDMS), after which they could take Interferon Beta-1b. Regression analyses including baseline age; sex; mono/multifocal onset; steroid treatment, EDSS score; gadolinium-enhancing (Gd+) and T2 lesion numbers; T2 and T1 hypointense lesion volume; presence of lesions in the spinal cord, optic nerve, or brainstem; PASAT score, and treatment assignment as covariates were conducted. P<.05 was used to identify significant associations. Results: 278 of 468 originally-randomized patients in BENEFIT were assessed at Year 11 (167, early treatment; 111, delayed treatment). In regression models, early treatment with Interferon Beta-1b, older age, lower number of Gd+ lesions, smaller T1 lesion volume, absence of steroid treatment, and absence of spinal cord lesions were significantly associated with longer time to CDMS. Older age, and male sex were associated with lower annualized relapse rate. Younger age, male sex, higher baseline EDSS, and lower Gd+ lesion count significantly predicted lower probability of a sustained 1-point EDSS progression. Higher likelihood of presence of clinical disease (≥1 relapse, CDMS, or EDSS progression) at Year 11 was significantly associated with higher number of Gd+ lesions. Conclusion: Analyses of patients after 11 years identified a number of baseline demographic, MRI, and clinical variables that predicted longer-term disease outcomes. Among other factors, assignment to earlier treatment with Interferon Beta-1b was associated with longer time to CDMS. Disclosure: MS Freedman has received compensation from Bayer HealthCare, Biogen Idec, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva Canada Innovation for consulting services. Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH. Dr. Edan has nothing to disclose. Dr. Montalban has received personal compensation for activities with Actelion, Almirall, Bayer Pharmaceuticals, Biogen Idec, Genzyme Corporation, Merck & Co., Inc., NeuroTex, Novartis, Octopharma, Receptos, and Roche Diagnostics Corporation as a speaker. Dr. Hartung has received personal compensation for activities with from Bayer, Biogen, GeNeuro, Genzyme as speaker, committee member, consultant. Dr. Hemmer has received personal compensation for activities with Roche, Novartis, Bayer Schering, Merck Serono, Biogen Idec, GSK, Chugai, Micromet and Genzyme Corporation as a scientific advisory board member. Dr. Fox has received research support from Biogen, Chugai, Eli Lily, EMD Serono, Genzyme, Novartis, Opexa, Roche. Dr. Barkhof has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, Genzyme, Janssen Research, Merck Serono, Novartis, Roche, Sanofi, Synthon BV, and Teva as a consultant. Dr. Schippling has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Teva, and Sanofi-Aventis as consultant and speaker. R. Koelbach has received personal compensation for activities with PAREXEL International as an employee. Dr. Pleimes has received personal compensation for activities with Myelo Therapeutics GmbH as an employee, and Bayer Pharmaceuticals Corporation as an employee and consultant. Dr. Suarez has received personal compensation for activities with Bayer Pharma AG/Bayer HealthCare Pharmaceuticals as an employee. Dr. Wicklein has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee.

  • long term impact of Interferon Beta 1b in patients with cis 8 year follow up of benefit
    Journal of Neurology Neurosurgery and Psychiatry, 2014
    Co-Authors: G Edan, Ludwig Kappos, H.-p. Hartung, M S Freedman, David H Miller, Xavier Montalban, C H Polman, F Barkhof, J Herrmann, Vivian Lanius
    Abstract:

    Objective To examine the long-term impact of early treatment initiation of Interferon Beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS). Methods In the original placebo-controlled phase of BENEFIT, patients were randomised to IFNB1b 250 μ go r placebo subcutaneously every other day. After 2 years or diagnosis of clinically definite MS (CDMS), all patients were offered open-label IFNB1b treatment for a maximum duration of 5 years. Thereafter, patients were enrolled in an observational extension study for up to 8.7 years. Results Of the initial 468 patients, 284 (60.7%; IFNB1b: 178 (61.0% of the original arm), placebo: 106 (60.2% of original arm)) were enrolled in the extension study. 94.2% of patients were receiving IFNB1b. Patients originally randomised to IFNB1b had a reduced risk of developing CDMS by 32.2% over the 8-year observation period (HR 0.678; 95% CI 0.525 to 0.875; p=0.0030), a longer median time to CDMS by 1345 days (95% CI 389 to 2301), and a lower annualised relapse rate (0.196 (95% CI 0.176 to 0.218) versus 0.255 (95% CI 0.226 to 0.287), p=0.0012), with differences mainly emerging in the first year of the study. Cognitive outcomes remained higher in the early treated patients. EDSS remained low over time with a median of 1.5 in both arms. Conclusions These 8-year results provide further evidence supporting early initiation of treatment with IFNB1b in patients with a first event suggestive of MS.

  • predicting response to Interferon Beta 1b therapy in patients with clinically isolated syndrome p1 228
    Neurology, 2014
    Co-Authors: M P Sormani, Ludwig Kappos, Frederik Barkhof, M S Freedman, G Edan, David H Miller, Xavier Montalban, Hans Hartung, Julia Hermann, Vivian Lanius
    Abstract:

    OBJECTIVE: To apply and validate the modRio score to discriminate response to Interferon Beta-1b (IFNB-1b) in patients with clinically isolated syndrome. BACKGROUND: Simple criteria for predicting treatment response in patients with first signs of multiple sclerosis (MS) are of great value. The modified Rio (modRio) score based on T2 lesions and clinical relapses over the first year of Interferon therapy has shown prognostic value for predicting disease activity in the subsequent years. DESIGN/METHODS: This post hoc analysis included 260 patients (IFNB-1b eod) from the BENEFIT study with MRI assessment at Month 12 and >=2 scheduled visits after Year 1 during a 5-year follow up. The score (0-3) was based on the number of new T2 lesions (>5) and clinical relapses (0, 1, or 2) during the first year of therapy. RESULTS: Of the 260 subjects meeting the inclusion criteria, 202 (77.7%) were in the low risk group (modRio score=0), whereas 43 (16.5%) and 15 (5.8%) were intermediate and high risk (modRio score 1 and 2, respectively) with no patients reaching a score 3. Annualized relapse rate [95% CI] from Year 1 to 5 for modRio 0, 1, and 2 were 0.14 [0.12-0.17], 0.30 [0.22-0.39], and 0.62 [0.43-0.86]. Sensitivity, specificity, and accuracy of modRio score >=1 (vs. 0) to predict >=1 relapses/year post Year 1 were 60.0%, 80.0%, and 78.8%. Confirmed EDSS progression from Year 1 up to Year 5 was observed in 40/202 patients (Kaplan Meier Estimate [KME]: 21%) for modRio score 0, in 11/ 43 (KME: 26%) for 1 and 5/15 (KME: 35.4%) for modRio score 2. CONCLUSIONS: The modRio score predicted response to IFNB-1b. Most patients in the BENEFIT cohort were low risk (score=0) according to the modRio criteria, and had a lower frequency of disease progression compared with those with modRio criteria 1 and 2. Study Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Dr. Sormani has received personal compensation for activities with Allozyne, Merck Serono, Teva Neuroscience, Synthon, Actelion and Biogen Idec. Dr. Barkhof has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Biogen Idec, Teva Neuroscience, Merck & Co. Inc., Novartis, Synthon BV, Janssen, Genzyme Inc., and Roche Diagnostics Corporation. Dr. Kappos has received personal compensation for activities with the University Hospital Basel. Dr. Kappos has received research support from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, Novartis, and Roche Diagnostics Corp. Dr. Edan has received personal compensation for activities with Bayer Pharmaceuticals Corp., Biogen Idec, Teva Neuroscience, Novartis, and LFB. Dr. Freedman has received personal compensation for activities with Actelion, Bayer, Biogen Idec, EMD Canada, Genzyme Corporation, Novartis, Opexa, Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Freedman has received research support from Bayer and Genzyme. Dr. Montalban has received personal compensation for activities with Bayer Pharmaceuticals Corp., BIogen Idec, EMD Serono, and Genente. Dr. Hartung has received personal compensation for activities with Bayer Pharmaceuticals Corp., CSL Behring, Biogen Idec, Genzyme Corp., Grifols, Merck Serono, Novartis, Roche Diagnostics Corp., Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals Inc. as a consultant and speaker. Dr. Miller has received personal compensation for activities with UCL Institute of Neurology, Biogen Idec, GlaxoSmithKline Inc., Novartis, Merck & Co. Inc., Chugai, and Mitsubishi Pharma. Dr. Miller has received personal compensation in an editorial capacity for the Journal of Neurology. Dr. Miller has received research support from Biogen Idec, Schering AG, Apitope, Richmond Pharma, GlaxoSmithKline Inc., and Novartis. Dr. Herrmann has received personal compensation for activities with PAREXEL International as an employee. Dr. Lanius has received personal compensation for activities with Bayer Pharmaceuticals Corp. as an employee. Dr. Beckmann has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee. Dr. Sandbrink has received personal compensation for activities with Bayer Pharmaceuticals Inc. Dr. Pohl has received personal compensation for activities with Bayer Pharmaceuticals Corp. Dr. Pleimes has received personal compensation for activities with Myelo Pharmaceuticals GmbH as an employee, and Bayer Pharmaceuticals Corp. as an employee and consultant.

  • vitamin d as predictor of multiple sclerosis activity and progression in patients with cis treated early with Interferon Beta 1b p5 016
    Neurology, 2014
    Co-Authors: Alberto Ascherio, M S Freedman, Xavier Montalban, Hans Hartung, Kassandra L Munger, Karl Kochert, Richard Allen White, Kelly Claire Simon, D W Miller, G Edan
    Abstract:

    OBJECTIVE: To examine the predictive effects of 25(OH)D on disease activity and prognosis in patients starting IFNB-1b at the CIS and the effect of 25(OH)D on the occurrence of flu-like symptoms (FLS) during treatment. BACKGROUND: The BENEFIT study examined the effects of Interferon Beta-1b (IFNB-1b) in clinically isolated syndrome (CIS). In prior analyses 25-hydroxyvitamin D (25[OH]D) contributed to the prediction of rate of conversion to clinically definite multiple sclerosis (CDMS), MS activity, and rate of progression up to 5-years after CIS. DESIGN/METHODS: Patients with a first clinical demyelinating event and >=2 clinically silent brain MRI lesions randomized to early IFNB-1b treatment with serum 25(OH)D concentration measurements at baseline, 6, 12, and 24 months were included. Clinical and MRI follow-up lasted for 5 years. Cox proportional hazard models or generalized mixed effects models related season-adjusted 25(OH)D concentrations to outcomes. Occurrence of FLS was compared by Chi-Square. RESULTS: Patients were dichotomized into high (>=50 nmol/L) and low ( 0.28). CONCLUSIONS: Among patients who started IFNB-1b treatment right after CIS, low 25(OH)D levels were a strong risk factor for long-term MS activity and severity but not for the occurrence of FLS, suggesting a role of vitamin D supplementation as an add-on to IFNB-1b in early treatment of patients with MS. Study Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Dr. Stolz has received personal compensation for activities with Precept Medical as an employee. Dr. Munger has nothing to disclose. Dr. White has received personal compensation for activities with Bayer Schering. Dr. Kochert has received personal compensation for activities with Bayer Pharmaceuticals Corp. as a consultant. Dr. Simon has nothing to disclose. Dr. Freedman has received personal compensation for activities with Actelion, Bayer, Biogen Idec, EMD Canada, Genzyme Corporation, Novartis, Opexa, Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Freedman has received research support from Bayer and Genzyme. Dr. Hartung has received personal compensation for activities with Bayer Pharmaceuticals Corp., CSL Behring, Biogen Idec, Genzyme Corp., Grifols, Merck Serono, Novartis, Roche Diagnostics Corp., Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals Inc. as a consultant and speaker. Dr. Miller has received personal compensation for activities with UCL Institute of Neurology, Biogen Idec, GlaxoSmithKline Inc., Novartis, Merck & Co. Inc., Chugai, and Mitsubishi Pharma. Dr. Miller has received personal compensation in an editorial capacity for the Journal of Neurology. Dr. Miller has received research support from Biogen Idec, Schering AG, Apitope, Richmond Pharma, GlaxoSmithKline Inc., and Novartis. Dr. Montalban has received personal compensation for activities with Bayer Pharmaceuticals Corp., BIogen Idec, EMD Serono, and Genente. Dr. Edan has received personal compensation for activities with Bayer Pharmaceuticals Corp., Biogen Idec, Teva Neuroscience, Novartis, and LFB. Dr. Barkhof has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Biogen Idec, Teva Neuroscience, Merck & Co. Inc., Novartis, Synthon BV, Janssen, Genzyme Inc., and Roche Diagnostics Corporation. Dr. Pleimes has received personal compensation for activities with Myelo Therapeutics GmbH as an employee, and with Bayer Pharmaceuticals Corp. as an employee and consultant. Dr. Sandbrink has received personal compensation for activities with Bayer Pharmaceuticals Inc. Dr. Kappos has received personal compensation for activities with the University Hospital Basel. Dr. Kappos has received research support from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, Novartis, and Roche Diagnostics Corp. Dr. Pohl has received personal compensation for activities with Bayer Pharmaceuticals Corp.

G Edan - One of the best experts on this subject based on the ideXlab platform.

  • The 11-year long-term follow-up study from the randomized BENEFIT CIS trial
    Neurology, 2016
    Co-Authors: Ludwig Kappos, Hanspeter Hartung, Frederik Barkhof, G Edan, Xavier Montalban, Bernhard Hemmer, Sven Schippling, Mark Freedman, Edward Fox, Andrea Schulze
    Abstract:

    Objective: To assess outcomes for patients treated with Interferon Beta-1b immediately after clinically isolated syndrome (CIS) or after a short delay. Methods: Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment) were randomly assigned to receive Interferon Beta-1b (early treatment) or placebo (delayed treatment). After conversion to clinically definite multiple sclerosis (CDMS) or 2 years, patients on placebo could switch to Interferon Beta-1b or another treatment. Eleven years after randomization, patients were reassessed. Results: Two hundred seventy-eight (59.4%) of the original 468 patients (71.3% of those eligible at participating sites) were enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm (p 5 0.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888 [540, not reached] vs 931 [253, 3,296]; p50.0005) and lower overall annualized relapse rate (0.21 vs 0.26; p50.0018). Only 25 patients (5.9%, overall; early, 4.5%; delayed, 8.3%) converted to secondary progressive multiple sclerosis. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms (median [Q1,Q3]: 2.0 [1.0, 3.0]). The early-treatment group had better Paced Auditory Serial Addition Task–3 total scores (p 5 0.0070). Employment rates remained high, and health resource utilization tended to be low in both groups.MRI metrics did not differ between groups. Conclusions: Although the delay in treatment was relatively short, several clinical outcomes favored earlier treatment. Along with low rates of disability and disease progression in both groups, this supports the value of treatment at CIS.

  • baseline predictors of disease activity in patients with cis treated with Interferon Beta 1b in the benefit 11 trial p2 121
    Neurology, 2016
    Co-Authors: M S Freedman, Ludwig Kappos, Frederik Barkhof, G Edan, Xavier Montalban, Hans Hartung, Bernhard Hemmer, Edward J Fox, Sven Schippling, R Koelbach
    Abstract:

    Objective: To analyze baseline patient characteristics for prediction of disease outcomes 11 years postrandomization. Background: A number of variables have been identified that are assessable early in the course of MS that may predict the disease course. Long-term follow up from the BENEFIT trial, which enrolled patients with clinically-isolated syndrome, is a unique opportunity to assess the predictive capacity of these variables. Methods: Patients were randomized to initial treatment with Interferon Beta-1b or placebo for 2 years or until diagnosis of clinically-definite multiple sclerosis (CDMS), after which they could take Interferon Beta-1b. Regression analyses including baseline age; sex; mono/multifocal onset; steroid treatment, EDSS score; gadolinium-enhancing (Gd+) and T2 lesion numbers; T2 and T1 hypointense lesion volume; presence of lesions in the spinal cord, optic nerve, or brainstem; PASAT score, and treatment assignment as covariates were conducted. P<.05 was used to identify significant associations. Results: 278 of 468 originally-randomized patients in BENEFIT were assessed at Year 11 (167, early treatment; 111, delayed treatment). In regression models, early treatment with Interferon Beta-1b, older age, lower number of Gd+ lesions, smaller T1 lesion volume, absence of steroid treatment, and absence of spinal cord lesions were significantly associated with longer time to CDMS. Older age, and male sex were associated with lower annualized relapse rate. Younger age, male sex, higher baseline EDSS, and lower Gd+ lesion count significantly predicted lower probability of a sustained 1-point EDSS progression. Higher likelihood of presence of clinical disease (≥1 relapse, CDMS, or EDSS progression) at Year 11 was significantly associated with higher number of Gd+ lesions. Conclusion: Analyses of patients after 11 years identified a number of baseline demographic, MRI, and clinical variables that predicted longer-term disease outcomes. Among other factors, assignment to earlier treatment with Interferon Beta-1b was associated with longer time to CDMS. Disclosure: MS Freedman has received compensation from Bayer HealthCare, Biogen Idec, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva Canada Innovation for consulting services. Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH. Dr. Edan has nothing to disclose. Dr. Montalban has received personal compensation for activities with Actelion, Almirall, Bayer Pharmaceuticals, Biogen Idec, Genzyme Corporation, Merck & Co., Inc., NeuroTex, Novartis, Octopharma, Receptos, and Roche Diagnostics Corporation as a speaker. Dr. Hartung has received personal compensation for activities with from Bayer, Biogen, GeNeuro, Genzyme as speaker, committee member, consultant. Dr. Hemmer has received personal compensation for activities with Roche, Novartis, Bayer Schering, Merck Serono, Biogen Idec, GSK, Chugai, Micromet and Genzyme Corporation as a scientific advisory board member. Dr. Fox has received research support from Biogen, Chugai, Eli Lily, EMD Serono, Genzyme, Novartis, Opexa, Roche. Dr. Barkhof has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, Genzyme, Janssen Research, Merck Serono, Novartis, Roche, Sanofi, Synthon BV, and Teva as a consultant. Dr. Schippling has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Teva, and Sanofi-Aventis as consultant and speaker. R. Koelbach has received personal compensation for activities with PAREXEL International as an employee. Dr. Pleimes has received personal compensation for activities with Myelo Therapeutics GmbH as an employee, and Bayer Pharmaceuticals Corporation as an employee and consultant. Dr. Suarez has received personal compensation for activities with Bayer Pharma AG/Bayer HealthCare Pharmaceuticals as an employee. Dr. Wicklein has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee.

  • magnetic resonance imaging effects of Interferon Beta 1b in the benefit study
    2015
    Co-Authors: Frederik Barkhof, Hanspeter Hartung, L. Kappos, Chris H Polman, Ernstwilhelm Radue, M S Freedman, G Edan, David H Miller, Peter Poppe, Marlieke De Vos
    Abstract:

    Results: Data were analyzed from 248 patients taking Interferon Beta-1b and 156 taking placebo. Across 2 years the cumulative number of newly active lesions was lower in patients receiving Interferon Beta-1b vs placebo (median, 2.0 vs 5.0 [reduction of 60%]; P.001). This corresponded to lower cumulative numbers of new T2 lesions (median, 1.0 vs 3.0 [reduction of 66%]; P.001) and new gadolinium-enhancing lesions (median, 0.0 vs 1.0; P .001) in patients receiving Interferon Beta-1b vs placebo. From screening to month 24, T2 lesion volume decreased and was more pronounced in patients receiving Interferon Beta-1b (P=.02). Conclusions: Interferon Beta-1b treatment had a robust effect on MRI measures, supporting its value as an early intervention in this patient group. This effect was maintained despite including patients who switched from placebo to Interferon Beta-1b in the active treatment group. Trial Registration: clinicaltrials.gov Identifier: NCT00185211

  • long term impact of Interferon Beta 1b in patients with cis 8 year follow up of benefit
    Journal of Neurology Neurosurgery and Psychiatry, 2014
    Co-Authors: G Edan, Ludwig Kappos, H.-p. Hartung, M S Freedman, David H Miller, Xavier Montalban, C H Polman, F Barkhof, J Herrmann, Vivian Lanius
    Abstract:

    Objective To examine the long-term impact of early treatment initiation of Interferon Beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS). Methods In the original placebo-controlled phase of BENEFIT, patients were randomised to IFNB1b 250 μ go r placebo subcutaneously every other day. After 2 years or diagnosis of clinically definite MS (CDMS), all patients were offered open-label IFNB1b treatment for a maximum duration of 5 years. Thereafter, patients were enrolled in an observational extension study for up to 8.7 years. Results Of the initial 468 patients, 284 (60.7%; IFNB1b: 178 (61.0% of the original arm), placebo: 106 (60.2% of original arm)) were enrolled in the extension study. 94.2% of patients were receiving IFNB1b. Patients originally randomised to IFNB1b had a reduced risk of developing CDMS by 32.2% over the 8-year observation period (HR 0.678; 95% CI 0.525 to 0.875; p=0.0030), a longer median time to CDMS by 1345 days (95% CI 389 to 2301), and a lower annualised relapse rate (0.196 (95% CI 0.176 to 0.218) versus 0.255 (95% CI 0.226 to 0.287), p=0.0012), with differences mainly emerging in the first year of the study. Cognitive outcomes remained higher in the early treated patients. EDSS remained low over time with a median of 1.5 in both arms. Conclusions These 8-year results provide further evidence supporting early initiation of treatment with IFNB1b in patients with a first event suggestive of MS.

  • predicting response to Interferon Beta 1b therapy in patients with clinically isolated syndrome p1 228
    Neurology, 2014
    Co-Authors: M P Sormani, Ludwig Kappos, Frederik Barkhof, M S Freedman, G Edan, David H Miller, Xavier Montalban, Hans Hartung, Julia Hermann, Vivian Lanius
    Abstract:

    OBJECTIVE: To apply and validate the modRio score to discriminate response to Interferon Beta-1b (IFNB-1b) in patients with clinically isolated syndrome. BACKGROUND: Simple criteria for predicting treatment response in patients with first signs of multiple sclerosis (MS) are of great value. The modified Rio (modRio) score based on T2 lesions and clinical relapses over the first year of Interferon therapy has shown prognostic value for predicting disease activity in the subsequent years. DESIGN/METHODS: This post hoc analysis included 260 patients (IFNB-1b eod) from the BENEFIT study with MRI assessment at Month 12 and >=2 scheduled visits after Year 1 during a 5-year follow up. The score (0-3) was based on the number of new T2 lesions (>5) and clinical relapses (0, 1, or 2) during the first year of therapy. RESULTS: Of the 260 subjects meeting the inclusion criteria, 202 (77.7%) were in the low risk group (modRio score=0), whereas 43 (16.5%) and 15 (5.8%) were intermediate and high risk (modRio score 1 and 2, respectively) with no patients reaching a score 3. Annualized relapse rate [95% CI] from Year 1 to 5 for modRio 0, 1, and 2 were 0.14 [0.12-0.17], 0.30 [0.22-0.39], and 0.62 [0.43-0.86]. Sensitivity, specificity, and accuracy of modRio score >=1 (vs. 0) to predict >=1 relapses/year post Year 1 were 60.0%, 80.0%, and 78.8%. Confirmed EDSS progression from Year 1 up to Year 5 was observed in 40/202 patients (Kaplan Meier Estimate [KME]: 21%) for modRio score 0, in 11/ 43 (KME: 26%) for 1 and 5/15 (KME: 35.4%) for modRio score 2. CONCLUSIONS: The modRio score predicted response to IFNB-1b. Most patients in the BENEFIT cohort were low risk (score=0) according to the modRio criteria, and had a lower frequency of disease progression compared with those with modRio criteria 1 and 2. Study Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Dr. Sormani has received personal compensation for activities with Allozyne, Merck Serono, Teva Neuroscience, Synthon, Actelion and Biogen Idec. Dr. Barkhof has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Biogen Idec, Teva Neuroscience, Merck & Co. Inc., Novartis, Synthon BV, Janssen, Genzyme Inc., and Roche Diagnostics Corporation. Dr. Kappos has received personal compensation for activities with the University Hospital Basel. Dr. Kappos has received research support from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, Novartis, and Roche Diagnostics Corp. Dr. Edan has received personal compensation for activities with Bayer Pharmaceuticals Corp., Biogen Idec, Teva Neuroscience, Novartis, and LFB. Dr. Freedman has received personal compensation for activities with Actelion, Bayer, Biogen Idec, EMD Canada, Genzyme Corporation, Novartis, Opexa, Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Freedman has received research support from Bayer and Genzyme. Dr. Montalban has received personal compensation for activities with Bayer Pharmaceuticals Corp., BIogen Idec, EMD Serono, and Genente. Dr. Hartung has received personal compensation for activities with Bayer Pharmaceuticals Corp., CSL Behring, Biogen Idec, Genzyme Corp., Grifols, Merck Serono, Novartis, Roche Diagnostics Corp., Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals Inc. as a consultant and speaker. Dr. Miller has received personal compensation for activities with UCL Institute of Neurology, Biogen Idec, GlaxoSmithKline Inc., Novartis, Merck & Co. Inc., Chugai, and Mitsubishi Pharma. Dr. Miller has received personal compensation in an editorial capacity for the Journal of Neurology. Dr. Miller has received research support from Biogen Idec, Schering AG, Apitope, Richmond Pharma, GlaxoSmithKline Inc., and Novartis. Dr. Herrmann has received personal compensation for activities with PAREXEL International as an employee. Dr. Lanius has received personal compensation for activities with Bayer Pharmaceuticals Corp. as an employee. Dr. Beckmann has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee. Dr. Sandbrink has received personal compensation for activities with Bayer Pharmaceuticals Inc. Dr. Pohl has received personal compensation for activities with Bayer Pharmaceuticals Corp. Dr. Pleimes has received personal compensation for activities with Myelo Pharmaceuticals GmbH as an employee, and Bayer Pharmaceuticals Corp. as an employee and consultant.

Ludwig Kappos - One of the best experts on this subject based on the ideXlab platform.

  • The 11-year long-term follow-up study from the randomized BENEFIT CIS trial
    Neurology, 2016
    Co-Authors: Ludwig Kappos, Hanspeter Hartung, Frederik Barkhof, G Edan, Xavier Montalban, Bernhard Hemmer, Sven Schippling, Mark Freedman, Edward Fox, Andrea Schulze
    Abstract:

    Objective: To assess outcomes for patients treated with Interferon Beta-1b immediately after clinically isolated syndrome (CIS) or after a short delay. Methods: Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment) were randomly assigned to receive Interferon Beta-1b (early treatment) or placebo (delayed treatment). After conversion to clinically definite multiple sclerosis (CDMS) or 2 years, patients on placebo could switch to Interferon Beta-1b or another treatment. Eleven years after randomization, patients were reassessed. Results: Two hundred seventy-eight (59.4%) of the original 468 patients (71.3% of those eligible at participating sites) were enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm (p 5 0.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888 [540, not reached] vs 931 [253, 3,296]; p50.0005) and lower overall annualized relapse rate (0.21 vs 0.26; p50.0018). Only 25 patients (5.9%, overall; early, 4.5%; delayed, 8.3%) converted to secondary progressive multiple sclerosis. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms (median [Q1,Q3]: 2.0 [1.0, 3.0]). The early-treatment group had better Paced Auditory Serial Addition Task–3 total scores (p 5 0.0070). Employment rates remained high, and health resource utilization tended to be low in both groups.MRI metrics did not differ between groups. Conclusions: Although the delay in treatment was relatively short, several clinical outcomes favored earlier treatment. Along with low rates of disability and disease progression in both groups, this supports the value of treatment at CIS.

  • baseline predictors of disease activity in patients with cis treated with Interferon Beta 1b in the benefit 11 trial p2 121
    Neurology, 2016
    Co-Authors: M S Freedman, Ludwig Kappos, Frederik Barkhof, G Edan, Xavier Montalban, Hans Hartung, Bernhard Hemmer, Edward J Fox, Sven Schippling, R Koelbach
    Abstract:

    Objective: To analyze baseline patient characteristics for prediction of disease outcomes 11 years postrandomization. Background: A number of variables have been identified that are assessable early in the course of MS that may predict the disease course. Long-term follow up from the BENEFIT trial, which enrolled patients with clinically-isolated syndrome, is a unique opportunity to assess the predictive capacity of these variables. Methods: Patients were randomized to initial treatment with Interferon Beta-1b or placebo for 2 years or until diagnosis of clinically-definite multiple sclerosis (CDMS), after which they could take Interferon Beta-1b. Regression analyses including baseline age; sex; mono/multifocal onset; steroid treatment, EDSS score; gadolinium-enhancing (Gd+) and T2 lesion numbers; T2 and T1 hypointense lesion volume; presence of lesions in the spinal cord, optic nerve, or brainstem; PASAT score, and treatment assignment as covariates were conducted. P<.05 was used to identify significant associations. Results: 278 of 468 originally-randomized patients in BENEFIT were assessed at Year 11 (167, early treatment; 111, delayed treatment). In regression models, early treatment with Interferon Beta-1b, older age, lower number of Gd+ lesions, smaller T1 lesion volume, absence of steroid treatment, and absence of spinal cord lesions were significantly associated with longer time to CDMS. Older age, and male sex were associated with lower annualized relapse rate. Younger age, male sex, higher baseline EDSS, and lower Gd+ lesion count significantly predicted lower probability of a sustained 1-point EDSS progression. Higher likelihood of presence of clinical disease (≥1 relapse, CDMS, or EDSS progression) at Year 11 was significantly associated with higher number of Gd+ lesions. Conclusion: Analyses of patients after 11 years identified a number of baseline demographic, MRI, and clinical variables that predicted longer-term disease outcomes. Among other factors, assignment to earlier treatment with Interferon Beta-1b was associated with longer time to CDMS. Disclosure: MS Freedman has received compensation from Bayer HealthCare, Biogen Idec, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva Canada Innovation for consulting services. Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH. Dr. Edan has nothing to disclose. Dr. Montalban has received personal compensation for activities with Actelion, Almirall, Bayer Pharmaceuticals, Biogen Idec, Genzyme Corporation, Merck & Co., Inc., NeuroTex, Novartis, Octopharma, Receptos, and Roche Diagnostics Corporation as a speaker. Dr. Hartung has received personal compensation for activities with from Bayer, Biogen, GeNeuro, Genzyme as speaker, committee member, consultant. Dr. Hemmer has received personal compensation for activities with Roche, Novartis, Bayer Schering, Merck Serono, Biogen Idec, GSK, Chugai, Micromet and Genzyme Corporation as a scientific advisory board member. Dr. Fox has received research support from Biogen, Chugai, Eli Lily, EMD Serono, Genzyme, Novartis, Opexa, Roche. Dr. Barkhof has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, Genzyme, Janssen Research, Merck Serono, Novartis, Roche, Sanofi, Synthon BV, and Teva as a consultant. Dr. Schippling has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Teva, and Sanofi-Aventis as consultant and speaker. R. Koelbach has received personal compensation for activities with PAREXEL International as an employee. Dr. Pleimes has received personal compensation for activities with Myelo Therapeutics GmbH as an employee, and Bayer Pharmaceuticals Corporation as an employee and consultant. Dr. Suarez has received personal compensation for activities with Bayer Pharma AG/Bayer HealthCare Pharmaceuticals as an employee. Dr. Wicklein has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee.

  • predictors of disease activity in 857 patients with ms treated with Interferon Beta 1b
    Journal of Neurology, 2015
    Co-Authors: Hanspeter Hartung, Giancarlo Comi, Massimo Filippi, Douglas Jeffery, Paul Oconnor, Barry G W Arnason, Stuart D Cook, Douglas S Goodin, Ludwig Kappos, John Petkau
    Abstract:

    Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disease of the CNS that requires long-term treatment. The identification of patient characteristics that can help predict disease outcomes could improve care for patients with MS. The objective of this study is to identify predictors of disease activity in patients from the BEYOND trial. This regression analysis of patients with relapsing–remitting MS from BEYOND examined the predictive value of patient characteristics at baseline and after 1 year of treatment with Interferon Beta-1b 250 μg every other day for clinical and MRI outcomes after year 1 of the study. 857 and 765 patients were included in the analyses of clinical and MRI outcomes, respectively. In multivariate analyses of age, a higher number of relapses in the past 2 years, ≥3 new MRI lesions in the first year, and, especially, a higher number of relapses in year 1 predicted the future occurrence of relapses. By contrast, age, MRI activity, and the presence of neutralizing antibodies in the first year were principally predictive of future MRI activity. In patients with continued clinical disease activity or substantial MRI activity on therapy, an alternative therapeutic approach should be strongly considered.

  • long term impact of Interferon Beta 1b in patients with cis 8 year follow up of benefit
    Journal of Neurology Neurosurgery and Psychiatry, 2014
    Co-Authors: G Edan, Ludwig Kappos, H.-p. Hartung, M S Freedman, David H Miller, Xavier Montalban, C H Polman, F Barkhof, J Herrmann, Vivian Lanius
    Abstract:

    Objective To examine the long-term impact of early treatment initiation of Interferon Beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS). Methods In the original placebo-controlled phase of BENEFIT, patients were randomised to IFNB1b 250 μ go r placebo subcutaneously every other day. After 2 years or diagnosis of clinically definite MS (CDMS), all patients were offered open-label IFNB1b treatment for a maximum duration of 5 years. Thereafter, patients were enrolled in an observational extension study for up to 8.7 years. Results Of the initial 468 patients, 284 (60.7%; IFNB1b: 178 (61.0% of the original arm), placebo: 106 (60.2% of original arm)) were enrolled in the extension study. 94.2% of patients were receiving IFNB1b. Patients originally randomised to IFNB1b had a reduced risk of developing CDMS by 32.2% over the 8-year observation period (HR 0.678; 95% CI 0.525 to 0.875; p=0.0030), a longer median time to CDMS by 1345 days (95% CI 389 to 2301), and a lower annualised relapse rate (0.196 (95% CI 0.176 to 0.218) versus 0.255 (95% CI 0.226 to 0.287), p=0.0012), with differences mainly emerging in the first year of the study. Cognitive outcomes remained higher in the early treated patients. EDSS remained low over time with a median of 1.5 in both arms. Conclusions These 8-year results provide further evidence supporting early initiation of treatment with IFNB1b in patients with a first event suggestive of MS.

  • predicting response to Interferon Beta 1b therapy in patients with clinically isolated syndrome p1 228
    Neurology, 2014
    Co-Authors: M P Sormani, Ludwig Kappos, Frederik Barkhof, M S Freedman, G Edan, David H Miller, Xavier Montalban, Hans Hartung, Julia Hermann, Vivian Lanius
    Abstract:

    OBJECTIVE: To apply and validate the modRio score to discriminate response to Interferon Beta-1b (IFNB-1b) in patients with clinically isolated syndrome. BACKGROUND: Simple criteria for predicting treatment response in patients with first signs of multiple sclerosis (MS) are of great value. The modified Rio (modRio) score based on T2 lesions and clinical relapses over the first year of Interferon therapy has shown prognostic value for predicting disease activity in the subsequent years. DESIGN/METHODS: This post hoc analysis included 260 patients (IFNB-1b eod) from the BENEFIT study with MRI assessment at Month 12 and >=2 scheduled visits after Year 1 during a 5-year follow up. The score (0-3) was based on the number of new T2 lesions (>5) and clinical relapses (0, 1, or 2) during the first year of therapy. RESULTS: Of the 260 subjects meeting the inclusion criteria, 202 (77.7%) were in the low risk group (modRio score=0), whereas 43 (16.5%) and 15 (5.8%) were intermediate and high risk (modRio score 1 and 2, respectively) with no patients reaching a score 3. Annualized relapse rate [95% CI] from Year 1 to 5 for modRio 0, 1, and 2 were 0.14 [0.12-0.17], 0.30 [0.22-0.39], and 0.62 [0.43-0.86]. Sensitivity, specificity, and accuracy of modRio score >=1 (vs. 0) to predict >=1 relapses/year post Year 1 were 60.0%, 80.0%, and 78.8%. Confirmed EDSS progression from Year 1 up to Year 5 was observed in 40/202 patients (Kaplan Meier Estimate [KME]: 21%) for modRio score 0, in 11/ 43 (KME: 26%) for 1 and 5/15 (KME: 35.4%) for modRio score 2. CONCLUSIONS: The modRio score predicted response to IFNB-1b. Most patients in the BENEFIT cohort were low risk (score=0) according to the modRio criteria, and had a lower frequency of disease progression compared with those with modRio criteria 1 and 2. Study Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Dr. Sormani has received personal compensation for activities with Allozyne, Merck Serono, Teva Neuroscience, Synthon, Actelion and Biogen Idec. Dr. Barkhof has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Biogen Idec, Teva Neuroscience, Merck & Co. Inc., Novartis, Synthon BV, Janssen, Genzyme Inc., and Roche Diagnostics Corporation. Dr. Kappos has received personal compensation for activities with the University Hospital Basel. Dr. Kappos has received research support from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, Novartis, and Roche Diagnostics Corp. Dr. Edan has received personal compensation for activities with Bayer Pharmaceuticals Corp., Biogen Idec, Teva Neuroscience, Novartis, and LFB. Dr. Freedman has received personal compensation for activities with Actelion, Bayer, Biogen Idec, EMD Canada, Genzyme Corporation, Novartis, Opexa, Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Freedman has received research support from Bayer and Genzyme. Dr. Montalban has received personal compensation for activities with Bayer Pharmaceuticals Corp., BIogen Idec, EMD Serono, and Genente. Dr. Hartung has received personal compensation for activities with Bayer Pharmaceuticals Corp., CSL Behring, Biogen Idec, Genzyme Corp., Grifols, Merck Serono, Novartis, Roche Diagnostics Corp., Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals Inc. as a consultant and speaker. Dr. Miller has received personal compensation for activities with UCL Institute of Neurology, Biogen Idec, GlaxoSmithKline Inc., Novartis, Merck & Co. Inc., Chugai, and Mitsubishi Pharma. Dr. Miller has received personal compensation in an editorial capacity for the Journal of Neurology. Dr. Miller has received research support from Biogen Idec, Schering AG, Apitope, Richmond Pharma, GlaxoSmithKline Inc., and Novartis. Dr. Herrmann has received personal compensation for activities with PAREXEL International as an employee. Dr. Lanius has received personal compensation for activities with Bayer Pharmaceuticals Corp. as an employee. Dr. Beckmann has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee. Dr. Sandbrink has received personal compensation for activities with Bayer Pharmaceuticals Inc. Dr. Pohl has received personal compensation for activities with Bayer Pharmaceuticals Corp. Dr. Pleimes has received personal compensation for activities with Myelo Pharmaceuticals GmbH as an employee, and Bayer Pharmaceuticals Corp. as an employee and consultant.

Frederik Barkhof - One of the best experts on this subject based on the ideXlab platform.

  • The 11-year long-term follow-up study from the randomized BENEFIT CIS trial
    Neurology, 2016
    Co-Authors: Ludwig Kappos, Hanspeter Hartung, Frederik Barkhof, G Edan, Xavier Montalban, Bernhard Hemmer, Sven Schippling, Mark Freedman, Edward Fox, Andrea Schulze
    Abstract:

    Objective: To assess outcomes for patients treated with Interferon Beta-1b immediately after clinically isolated syndrome (CIS) or after a short delay. Methods: Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment) were randomly assigned to receive Interferon Beta-1b (early treatment) or placebo (delayed treatment). After conversion to clinically definite multiple sclerosis (CDMS) or 2 years, patients on placebo could switch to Interferon Beta-1b or another treatment. Eleven years after randomization, patients were reassessed. Results: Two hundred seventy-eight (59.4%) of the original 468 patients (71.3% of those eligible at participating sites) were enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm (p 5 0.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888 [540, not reached] vs 931 [253, 3,296]; p50.0005) and lower overall annualized relapse rate (0.21 vs 0.26; p50.0018). Only 25 patients (5.9%, overall; early, 4.5%; delayed, 8.3%) converted to secondary progressive multiple sclerosis. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms (median [Q1,Q3]: 2.0 [1.0, 3.0]). The early-treatment group had better Paced Auditory Serial Addition Task–3 total scores (p 5 0.0070). Employment rates remained high, and health resource utilization tended to be low in both groups.MRI metrics did not differ between groups. Conclusions: Although the delay in treatment was relatively short, several clinical outcomes favored earlier treatment. Along with low rates of disability and disease progression in both groups, this supports the value of treatment at CIS.

  • baseline predictors of disease activity in patients with cis treated with Interferon Beta 1b in the benefit 11 trial p2 121
    Neurology, 2016
    Co-Authors: M S Freedman, Ludwig Kappos, Frederik Barkhof, G Edan, Xavier Montalban, Hans Hartung, Bernhard Hemmer, Edward J Fox, Sven Schippling, R Koelbach
    Abstract:

    Objective: To analyze baseline patient characteristics for prediction of disease outcomes 11 years postrandomization. Background: A number of variables have been identified that are assessable early in the course of MS that may predict the disease course. Long-term follow up from the BENEFIT trial, which enrolled patients with clinically-isolated syndrome, is a unique opportunity to assess the predictive capacity of these variables. Methods: Patients were randomized to initial treatment with Interferon Beta-1b or placebo for 2 years or until diagnosis of clinically-definite multiple sclerosis (CDMS), after which they could take Interferon Beta-1b. Regression analyses including baseline age; sex; mono/multifocal onset; steroid treatment, EDSS score; gadolinium-enhancing (Gd+) and T2 lesion numbers; T2 and T1 hypointense lesion volume; presence of lesions in the spinal cord, optic nerve, or brainstem; PASAT score, and treatment assignment as covariates were conducted. P<.05 was used to identify significant associations. Results: 278 of 468 originally-randomized patients in BENEFIT were assessed at Year 11 (167, early treatment; 111, delayed treatment). In regression models, early treatment with Interferon Beta-1b, older age, lower number of Gd+ lesions, smaller T1 lesion volume, absence of steroid treatment, and absence of spinal cord lesions were significantly associated with longer time to CDMS. Older age, and male sex were associated with lower annualized relapse rate. Younger age, male sex, higher baseline EDSS, and lower Gd+ lesion count significantly predicted lower probability of a sustained 1-point EDSS progression. Higher likelihood of presence of clinical disease (≥1 relapse, CDMS, or EDSS progression) at Year 11 was significantly associated with higher number of Gd+ lesions. Conclusion: Analyses of patients after 11 years identified a number of baseline demographic, MRI, and clinical variables that predicted longer-term disease outcomes. Among other factors, assignment to earlier treatment with Interferon Beta-1b was associated with longer time to CDMS. Disclosure: MS Freedman has received compensation from Bayer HealthCare, Biogen Idec, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva Canada Innovation for consulting services. Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH. Dr. Edan has nothing to disclose. Dr. Montalban has received personal compensation for activities with Actelion, Almirall, Bayer Pharmaceuticals, Biogen Idec, Genzyme Corporation, Merck & Co., Inc., NeuroTex, Novartis, Octopharma, Receptos, and Roche Diagnostics Corporation as a speaker. Dr. Hartung has received personal compensation for activities with from Bayer, Biogen, GeNeuro, Genzyme as speaker, committee member, consultant. Dr. Hemmer has received personal compensation for activities with Roche, Novartis, Bayer Schering, Merck Serono, Biogen Idec, GSK, Chugai, Micromet and Genzyme Corporation as a scientific advisory board member. Dr. Fox has received research support from Biogen, Chugai, Eli Lily, EMD Serono, Genzyme, Novartis, Opexa, Roche. Dr. Barkhof has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, Genzyme, Janssen Research, Merck Serono, Novartis, Roche, Sanofi, Synthon BV, and Teva as a consultant. Dr. Schippling has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Teva, and Sanofi-Aventis as consultant and speaker. R. Koelbach has received personal compensation for activities with PAREXEL International as an employee. Dr. Pleimes has received personal compensation for activities with Myelo Therapeutics GmbH as an employee, and Bayer Pharmaceuticals Corporation as an employee and consultant. Dr. Suarez has received personal compensation for activities with Bayer Pharma AG/Bayer HealthCare Pharmaceuticals as an employee. Dr. Wicklein has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee.

  • magnetic resonance imaging effects of Interferon Beta 1b in the benefit study
    2015
    Co-Authors: Frederik Barkhof, Hanspeter Hartung, L. Kappos, Chris H Polman, Ernstwilhelm Radue, M S Freedman, G Edan, David H Miller, Peter Poppe, Marlieke De Vos
    Abstract:

    Results: Data were analyzed from 248 patients taking Interferon Beta-1b and 156 taking placebo. Across 2 years the cumulative number of newly active lesions was lower in patients receiving Interferon Beta-1b vs placebo (median, 2.0 vs 5.0 [reduction of 60%]; P.001). This corresponded to lower cumulative numbers of new T2 lesions (median, 1.0 vs 3.0 [reduction of 66%]; P.001) and new gadolinium-enhancing lesions (median, 0.0 vs 1.0; P .001) in patients receiving Interferon Beta-1b vs placebo. From screening to month 24, T2 lesion volume decreased and was more pronounced in patients receiving Interferon Beta-1b (P=.02). Conclusions: Interferon Beta-1b treatment had a robust effect on MRI measures, supporting its value as an early intervention in this patient group. This effect was maintained despite including patients who switched from placebo to Interferon Beta-1b in the active treatment group. Trial Registration: clinicaltrials.gov Identifier: NCT00185211

  • predicting response to Interferon Beta 1b therapy in patients with clinically isolated syndrome p1 228
    Neurology, 2014
    Co-Authors: M P Sormani, Ludwig Kappos, Frederik Barkhof, M S Freedman, G Edan, David H Miller, Xavier Montalban, Hans Hartung, Julia Hermann, Vivian Lanius
    Abstract:

    OBJECTIVE: To apply and validate the modRio score to discriminate response to Interferon Beta-1b (IFNB-1b) in patients with clinically isolated syndrome. BACKGROUND: Simple criteria for predicting treatment response in patients with first signs of multiple sclerosis (MS) are of great value. The modified Rio (modRio) score based on T2 lesions and clinical relapses over the first year of Interferon therapy has shown prognostic value for predicting disease activity in the subsequent years. DESIGN/METHODS: This post hoc analysis included 260 patients (IFNB-1b eod) from the BENEFIT study with MRI assessment at Month 12 and >=2 scheduled visits after Year 1 during a 5-year follow up. The score (0-3) was based on the number of new T2 lesions (>5) and clinical relapses (0, 1, or 2) during the first year of therapy. RESULTS: Of the 260 subjects meeting the inclusion criteria, 202 (77.7%) were in the low risk group (modRio score=0), whereas 43 (16.5%) and 15 (5.8%) were intermediate and high risk (modRio score 1 and 2, respectively) with no patients reaching a score 3. Annualized relapse rate [95% CI] from Year 1 to 5 for modRio 0, 1, and 2 were 0.14 [0.12-0.17], 0.30 [0.22-0.39], and 0.62 [0.43-0.86]. Sensitivity, specificity, and accuracy of modRio score >=1 (vs. 0) to predict >=1 relapses/year post Year 1 were 60.0%, 80.0%, and 78.8%. Confirmed EDSS progression from Year 1 up to Year 5 was observed in 40/202 patients (Kaplan Meier Estimate [KME]: 21%) for modRio score 0, in 11/ 43 (KME: 26%) for 1 and 5/15 (KME: 35.4%) for modRio score 2. CONCLUSIONS: The modRio score predicted response to IFNB-1b. Most patients in the BENEFIT cohort were low risk (score=0) according to the modRio criteria, and had a lower frequency of disease progression compared with those with modRio criteria 1 and 2. Study Supported by: Bayer HealthCare Pharmaceuticals Disclosure: Dr. Sormani has received personal compensation for activities with Allozyne, Merck Serono, Teva Neuroscience, Synthon, Actelion and Biogen Idec. Dr. Barkhof has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Biogen Idec, Teva Neuroscience, Merck & Co. Inc., Novartis, Synthon BV, Janssen, Genzyme Inc., and Roche Diagnostics Corporation. Dr. Kappos has received personal compensation for activities with the University Hospital Basel. Dr. Kappos has received research support from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, Novartis, and Roche Diagnostics Corp. Dr. Edan has received personal compensation for activities with Bayer Pharmaceuticals Corp., Biogen Idec, Teva Neuroscience, Novartis, and LFB. Dr. Freedman has received personal compensation for activities with Actelion, Bayer, Biogen Idec, EMD Canada, Genzyme Corporation, Novartis, Opexa, Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Freedman has received research support from Bayer and Genzyme. Dr. Montalban has received personal compensation for activities with Bayer Pharmaceuticals Corp., BIogen Idec, EMD Serono, and Genente. Dr. Hartung has received personal compensation for activities with Bayer Pharmaceuticals Corp., CSL Behring, Biogen Idec, Genzyme Corp., Grifols, Merck Serono, Novartis, Roche Diagnostics Corp., Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals Inc. as a consultant and speaker. Dr. Miller has received personal compensation for activities with UCL Institute of Neurology, Biogen Idec, GlaxoSmithKline Inc., Novartis, Merck & Co. Inc., Chugai, and Mitsubishi Pharma. Dr. Miller has received personal compensation in an editorial capacity for the Journal of Neurology. Dr. Miller has received research support from Biogen Idec, Schering AG, Apitope, Richmond Pharma, GlaxoSmithKline Inc., and Novartis. Dr. Herrmann has received personal compensation for activities with PAREXEL International as an employee. Dr. Lanius has received personal compensation for activities with Bayer Pharmaceuticals Corp. as an employee. Dr. Beckmann has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee. Dr. Sandbrink has received personal compensation for activities with Bayer Pharmaceuticals Inc. Dr. Pohl has received personal compensation for activities with Bayer Pharmaceuticals Corp. Dr. Pleimes has received personal compensation for activities with Myelo Pharmaceuticals GmbH as an employee, and Bayer Pharmaceuticals Corp. as an employee and consultant.

  • long term effect of early treatment with Interferon Beta 1b after a first clinical event suggestive of multiple sclerosis 5 year active treatment extension of the phase 3 benefit trial
    Lancet Neurology, 2009
    Co-Authors: Ludwig Kappos, Hanspeter Hartung, Frederik Barkhof, Chris H Polman, M S Freedman, G Edan, David H Miller, Xavier Montalban, E W Radu, Carola Metzig
    Abstract:

    BACKGROUND: The Betaferon/Betaseron in newly emerging multiple sclerosis for initial treatment (BENEFIT) trial investigated the effect of treatment with Interferon Beta-1b after a clinically isolated syndrome. The 5-year active treatment extension compares the effects of early and delayed treatment with Interferon Beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression. METHODS: Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive Interferon Beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label Interferon Beta-1b up to a maximum of 5 years after randomisation. Patients and study personnel remained unaware of initial treatment allocation throughout the study. Primary endpoints were time to CDMS, time to confirmed disability progression measured with the expanded disability status scale, and the functional assessment of multiple sclerosis trial outcomes index (FAMS-TOI) at 5 years. Analysis of the primary endpoints was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00185211. FINDINGS: 235 (80%) patients from the early treatment and 123 (70%) from the delayed treatment group completed the 5-year study. Early treatment reduced the risk of CDMS by 37% (hazard ratio [HR] 0.63, 95% CI 0.48-0.83; p=0.003) compared with delayed treatment. The risk for confirmed disability progression was not significantly lower in the early treatment group (0.76, 0.52-1.11; p=0.177). At 5 years, median FAMS-TOI scores were 125 in both groups. No significant differences in other disability related outcomes were recorded. Frequency and severity of adverse events remained within the established safety and tolerability profile of Interferon Beta-1b. INTERPRETATION: Effects on the rate of conversion to CDMS and the favourable long-term safety and tolerability profile support early initiation of treatment with Interferon Beta-1b, although a delay in treatment by up to 2 years did not affect long-term disability outcomes. FUNDING: Bayer Schering Pharma.

Thomas Glaser - One of the best experts on this subject based on the ideXlab platform.

  • sleep quality daytime sleepiness fatigue and quality of life in patients with multiple sclerosis treated with Interferon Beta 1b results from a prospective observational cohort study
    BMC Neurology, 2018
    Co-Authors: Sylvia Kotterba, Thomas Glaser, Christiane Norenberg, Thomas Neusser, Patrick Bussfeld, Martin Dorner, Markus Schurks
    Abstract:

    Sleep disorders and fatigue are common in multiple sclerosis (MS). The underlying causes are not fully understood, and prospective studies are lacking. Therefore, we conducted a prospective, observational cohort study investigating sleep quality, fatigue, quality of life, and comorbidities in patients with MS. Patients with relapsing-remitting MS or clinically isolated syndrome treated with Interferon Beta-1b were followed over two years. The primary objective was to investigate correlations between sleep quality (PSQI), fatigue (MFIS), and functional health status (SF-36). Secondary objectives were to investigate correlations of sleep quality and daytime sleepiness (ESS), depression (HADS-D), anxiety (HADS-A), pain (HSAL), and restless legs syndrome (RLS). We applied descriptive statistics, correlation and regression analyses. 139 patients were enrolled, 128 were available for full analysis. The proportion of poor sleepers (PSQI≥5) was 55.47% at the beginning and 37.70% by the end of the study (106 and 41 evaluable questionnaires, respectively). Poor sleepers performed worse in MFIS, SF-36, ESS, HADS-D, and HADS-A scores. The prevalence of patients with RLS was low (4.5%) and all were poor sleepers. Poor sleep quality was positively correlated with fatigue and low functional health status. These relationships were corroborated by multivariable-adjusted regression analyses. ESS values and poor sleep quality at baseline seem to predict sleep quality at the one-year follow-up. No variable predicted sleep quality at the two-year follow-up. Our results confirm the high prevalence of poor sleep quality among patients with MS and its persistent correlation with fatigue and reduced quality of life over time. They highlight the importance of interventions to improve sleep quality. The study was registered at clinicaltrials.gov: NCT01766063 (registered December 7, 2012). Registered retrospectively (first patient enrolled December 6, 2012).

  • Sleep quality, daytime sleepiness, fatigue, and quality of life in patients with multiple sclerosis treated with Interferon Beta-1b: results from a prospective observational cohort study
    BMC, 2018
    Co-Authors: Sylvia Kotterba, Thomas Glaser, Christiane Norenberg, Thomas Neusser, Patrick Bussfeld, Martin Dorner, Markus Schurks
    Abstract:

    Abstract Background Sleep disorders and fatigue are common in multiple sclerosis (MS). The underlying causes are not fully understood, and prospective studies are lacking. Therefore, we conducted a prospective, observational cohort study investigating sleep quality, fatigue, quality of life, and comorbidities in patients with MS. Methods Patients with relapsing-remitting MS or clinically isolated syndrome treated with Interferon Beta-1b were followed over two years. The primary objective was to investigate correlations between sleep quality (PSQI), fatigue (MFIS), and functional health status (SF-36). Secondary objectives were to investigate correlations of sleep quality and daytime sleepiness (ESS), depression (HADS-D), anxiety (HADS-A), pain (HSAL), and restless legs syndrome (RLS). We applied descriptive statistics, correlation and regression analyses. Results 139 patients were enrolled, 128 were available for full analysis. The proportion of poor sleepers (PSQI≥5) was 55.47% at the beginning and 37.70% by the end of the study (106 and 41 evaluable questionnaires, respectively). Poor sleepers performed worse in MFIS, SF-36, ESS, HADS-D, and HADS-A scores. The prevalence of patients with RLS was low (4.5%) and all were poor sleepers. Poor sleep quality was positively correlated with fatigue and low functional health status. These relationships were corroborated by multivariable-adjusted regression analyses. ESS values and poor sleep quality at baseline seem to predict sleep quality at the one-year follow-up. No variable predicted sleep quality at the two-year follow-up. Conclusions Our results confirm the high prevalence of poor sleep quality among patients with MS and its persistent correlation with fatigue and reduced quality of life over time. They highlight the importance of interventions to improve sleep quality. Trial registration The study was registered at clinicaltrials.gov: NCT01766063 (registered December 7, 2012). Registered retrospectively (first patient enrolled December 6, 2012)

  • comparative evaluation of patients and physicians satisfaction with Interferon Beta 1b therapy
    BMC Neurology, 2016
    Co-Authors: Uwe K Zettl, Ulrike Bauersteinhusen, Thomas Glaser, Klaus Hechenbichler, Michael Hecker
    Abstract:

    Due to the preventive nature of disease-modifying therapies for multiple sclerosis, treatment success particularly depends on adherence to therapeutic regimens and patients’ perception of treatment efficacy. The latter is strongly influenced by the confidence in the involved health care professionals and the relationship to the treating physician. In this report, we considered physicians’ and patients’ evaluation of satisfaction with Interferon Beta-1b treatment efficacy for assessing the congruence in ratings. Data were queried in a study conducted between 2009 and 2013. After 6 months of therapy, > 80 % of the patients and physicians (N = 445) showed high degrees of satisfaction regarding Interferon Beta-1b treatment, with only few physicians and patients (≤2.0 %) rating “not satisfied”. The proportion of patients rating with the same category as their physicians was similar after 6 months (47 % congruence) and at the 24 months/study end visit (49 %). Discrepancies between ratings were observed with respect to study end: for patients with premature study end, more patients and physicians rated being not satisfied with the therapy, accompanied by a considerably lower congruence of 33 % compared to 54 % for patients receiving the therapy for at least 2 years and completing the study regularly. Regular communication between physicians and patients about their perception of therapy might improve alignment of treatment evaluation and could result in increased therapy persistence. In addition, patients’ willingness to perform a long-term therapy − even in the absence of disease symptoms − might be promoted by repeated exchange between health care providers and patients with regard to realistic treatment expectations. ClinicalTrials.gov NCT00902135 (registered May 13, 2009).

  • evaluation of an electronic diary for improvement of adherence to Interferon Beta 1b in patients with multiple sclerosis design and baseline results of an observational cohort study
    BMC Neurology, 2013
    Co-Authors: Uwe K Zettl, Ulrike Bauersteinhusen, Thomas Glaser, Klaus Hechenbichler, Volker Limmroth
    Abstract:

    Multiple sclerosis is a chronic, incurable, demyelinating disease that requires long-term treatment. Rates of non-adherence to prescribed therapy of up to 50% have been reported for chronic diseases. Strategies to improve treatment adherence are therefore of the utmost importance. This study will evaluate the effect of using electronic and paper diaries on treatment adherence to Interferon Beta-1b in patients with a first clinical isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS). Here we report on the study design and results of baseline assessments. Patients were recruited into a prospective national multicenter cohort study for an observational period of 2 years. At the start of the study, patients opted to use a digital (DiD) or paper diary (PD) to document self-administered injections of Interferon Beta-1b. Adherence to treatment will be assessed on the dropout rate at the end of the observation period and on the regularity of injections every other day at 6-month intervals. Patient-related health outcomes will also be evaluated. 700 patients with a mean age of 38.3 (SD 10.3) years and a mean duration of disease since diagnosis of 3.6 (SD 5.9) years were enrolled. 383 patients opted for the digital diary, 192 of which included an injection reminder. Significantly more male than female patients opted for the DiD. Only gender was identified as a factor influencing the decision for DiD or PD. Based on rating scales, a significantly higher proportion of women had depressive comorbidities at baseline. Demographic characteristics of the two cohorts were similar at baseline. More women chose a paper diary, and more had depression at baseline. These imbalances will be addressed in the analysis of the study as possible confounders influencing long-term treatment adherence in the digital and paper diary cohorts. ClinicalTrials.gov Identifier: NCT00902135 .