Contributions
Abstract: P643
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Introduction: Course, progression of disability and response to treatment are highly variable in multiple sclerosis (MS). Several cerebrospinal fluid (CSF) parameters have been suggested as possible prognostic markers to predict disease activity and progression. Intrathecal immunoglobulin (IG) synthesis is frequently seen in patients with MS and clinically isolated syndrome (CIS) and may reflect the extent of humoral immune response in the CNS. The aim of this study was to investigate the association between intrathecal IG synthesis and EDSS progression in the national German MS cohort, a large prospective cohort of patients with newly diagnosed relapsing remitting MS (RRMS) or CIS.
Methods: 375 CIS and RRMS patients from the national German MS cohort with available detailed CSF data and a clinical follow up over two years were included in the analysis. The association between intrathecal IG synthesis (synthesis of at least one of the IG subclasses IgG, IgA and IgM) and risk of expanded disability status scale (EDSS) progression within two years was tested by binomial regression with adjustments made for age and sex. Additionally, Kaplan-Meier analysis with a log-rank test was used to assess intrathecal IG synthesis as a prognostic factor for time to EDSS progression.
Results: The presence of intrathecal IG synthesis was significantly associated with higher risk of EDSS progression within two years (p=0.01). This effect was even more pronounced for patients who had not been treated with disease modifying drugs (p=8E-3). Additionally, intrathecal IG synthesis was associated with a shorter time to EDSS progression (p=0.035). Subanalyses showed that the effect was mainly driven by intrathecal IgG synthesis.
Conclusion: In this study newly diagnosed MS or CIS patients with intrathecal IG synthesis had a higher risk of and shorter times to EDSS progression within two years. This demonstrates a potential predictive value of a standard CSF parameter for disease progression in MS. Follow-up studies will address whether CSF parameters also predict long-term outcome in newly diagnosed CIS and MS patients.
Disclosure:
C. Gasperi: nothing to disclose.
A. Salmen has received speaker honoraria and/or travel compensation for activities with Almirall Hermal GmbH, Biogen, Merck, Novartis, Roche and Sanofi Genzyme, none related to this work.
G. Antony: nothing to disclose.
A. Bayas received personal compensation from Merck, Biogen, Bayer Vital, Novartis, TEVA, Roche and Sanofi/Genzyme and grants for congress trips and participation from Biogen, TEVA, Novartis, Sanofi/Genzyme and Merck.
T. Dankowski: nothing to disclose.
C. Heesen has received speaker honoraria and grants from Biogen, Genzyme, Roche and Merck.
T. Kümpfel has received travel expenses and personal compensations from Bayer Healthcare, Teva Pharma, Merck-Serono, Novartis, Sanofi-Aventis/Genzyme, Roche and Biogen as well as grant support from Bayer-Schering AG, Novartis and Chugai Pharma.
R.A. Linker received research support and/or personal compensation for activities with Bayer Health Care, Biogen, Genzyme/Sanofi, Merck, Novartis Pharma, Roche and TEVA Pharma.
F. Paul served on the steering committee for Novartis OCTIMS study and MedImmune; received speaker honoraria and travel funding from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, and MedImmune; is an academic editor for PLoS One; is an associate editor for Neurology®: Neuroimmunology & Neuroinflammation; has consulted for SanofiGenzyme, Biogen Idec, and MedImmune; and received research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research (BMBF Competence Network Multiple Sclerosis), and Arthur Arnstein Stiftung Berlin.
M. Stangel has received honoraria for scientific lectures or consultancy from Bayer Healthcare, Biogen, Baxter/Baxalta, CSL Behring, Euroimmune, Grifols, Merck-Serono, Novartis, Roche, Sanofi-Aventis, and Teva. His institution received research support from Bayer Healthcare, Biogen Idec, Genzyme, Merck-Serono, Novartis, and Teva.
B. Tackenberg received personal speaker honoraria and consultancy fees as a speaker and advisor from Bayer Healthcare, Biogen, CSL Behring, GRIFOLS, Merck Serono, Novartis, Octapharma, Roche, Sanofi Genzyme, TEVA und UCB Pharma. His University received unrestricted research grants from Biogen-idec, Novartis, TEVA, Bayer Healthcare, CSL-Behring, GRIFOLS, Octapharma, Sanofi Genzyme und UCB Pharma.
F. Then Bergh has no conflicts of interest with respect to the contents of this abstract. Within the past year before abstract submission, he received funding from the DFG; received, through his institution, research support for investigator-initiated studies from Actelion and Novartis; has served on scientific advisory boards for Novartis, Sanofi/Genzyme and Roche; has received support to attend a scientific meeting from Biogen; and has received personal honoraria for speaking from Bayer Schering, Biogen, Roche and Sanofi/Genzyme.
H. Tumani received speaker honoraria from Bayer, Biogen, Fresenius, Genzyme, Merck, Novartis, Roche, Siemens, Teva; serves as section editor for the Journal of Neurology, Psychiatry and Brain Research; and receives research support from Fresenius, Genzyme, Merck and Novartis, none related to this work.
C. Warnke received honoraria and/or research funding from Bayer, Biogen, Novartis and TEVA.
F. Weber received honoraria from Genzyme, Novartis TEVA and Biogen for speaking or for serving on a scientific advisory board, a travel grant for the attention of a scientific meeting from Merck-Serono and Novartis and grant support from Merck-Serono, Novartis and from the Federal Ministry of Education and Research (BMBF, Projects Biobanking and Omics in ControlMS as part of the Competence Network Multiple Sclerosis).
H. Wiendl receives honoraria for acting as a member of Scientific Advisory Boards and as consultant for Biogen, Evgen, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, as well as speaker honoraria and travel support from Alexion, Biogen, Cognomed, F. Hoffmann-La Roche Ltd., Gemeinnützige Hertie-Stiftung, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA, and WebMD Global. Prof. Wiendl is acting as a paid consultant for Abbvie, Actelion, Biogen, IGES, Novartis, Roche, Sanofi-Genzyme, and the Swiss Multiple Sclerosis Society. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Else Kröner Fresenius Foundation, Fresenius Foundation, Hertie Foundation, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies (IZKF) Muenster and RE Children's Foundation, Biogen GmbH, GlaxoSmithKline GmbH, Roche Pharma AG, Sanofi-Genzyme.
B. Wildemann received grants from the German Ministry of Education and Research, Dietmar Hopp Foundation and Klaus Tschira Foundation, grants and personal fees from Biogen, Merck Serono, Sanofi Genzyme, Novartis pharmaceuticals, Teva Pharma, and personal fees from Bayer Healthcare.
U.K. Zettl received no financial support for the research, authorship, and/or publication of this abstract.
U. Ziemann has received speaker honoraria and/or travel compensation from Biogen Idec GmbH, Bayer Vital GmbH, Bristol Myers Squibb GmbH, CorTec GmbH, Medtronic GmbH, and grants from Biogen Idec GmbH, Servier, and Janssen Pharmaceuticals NV, outside of the submitted work.
F. Zipp has received research grants from Teva, Merck Serono, Novartis and Bayer as well as consultation funds from Teva, Merck Serono, Novartis, Bayer Healthcare, Biogen Idec Germany, ONO, Genzyme, Sanofi-Aventis and Octapharma. Her travel compensation has been provided for by the aforementioned companies.
R. Gold received speaker's and board honoraria from Baxter, Bayer Schering, Biogen Idec, CLB Behring, Genzyme, Merck Serono, Novartis, Stendhal, Talecris, TEVA. His department received grant support from Bayer Schering, BiogenIdec, Genzyme, Merck Serono, Novartis, TEVA.
B. Hemmer has served on scientific advisory boards for F. Hoffmann-La Roche Ltd, Novartis, Bayer AG, and Genentech; he has served as DMSC member for AllergyCare; he or his institution have received speaker honoraria from Biogen Idec, Teva Neuroscience, Merck Serono, Medimmune, Novartis, Desitin, and F. Hoffmann-La Roche Ltd; his institution has received research support from Chugai Pharmaceuticals and Hoffmann-La-Roche; holds part of two patents; one for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon β.
Abstract: P643
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Introduction: Course, progression of disability and response to treatment are highly variable in multiple sclerosis (MS). Several cerebrospinal fluid (CSF) parameters have been suggested as possible prognostic markers to predict disease activity and progression. Intrathecal immunoglobulin (IG) synthesis is frequently seen in patients with MS and clinically isolated syndrome (CIS) and may reflect the extent of humoral immune response in the CNS. The aim of this study was to investigate the association between intrathecal IG synthesis and EDSS progression in the national German MS cohort, a large prospective cohort of patients with newly diagnosed relapsing remitting MS (RRMS) or CIS.
Methods: 375 CIS and RRMS patients from the national German MS cohort with available detailed CSF data and a clinical follow up over two years were included in the analysis. The association between intrathecal IG synthesis (synthesis of at least one of the IG subclasses IgG, IgA and IgM) and risk of expanded disability status scale (EDSS) progression within two years was tested by binomial regression with adjustments made for age and sex. Additionally, Kaplan-Meier analysis with a log-rank test was used to assess intrathecal IG synthesis as a prognostic factor for time to EDSS progression.
Results: The presence of intrathecal IG synthesis was significantly associated with higher risk of EDSS progression within two years (p=0.01). This effect was even more pronounced for patients who had not been treated with disease modifying drugs (p=8E-3). Additionally, intrathecal IG synthesis was associated with a shorter time to EDSS progression (p=0.035). Subanalyses showed that the effect was mainly driven by intrathecal IgG synthesis.
Conclusion: In this study newly diagnosed MS or CIS patients with intrathecal IG synthesis had a higher risk of and shorter times to EDSS progression within two years. This demonstrates a potential predictive value of a standard CSF parameter for disease progression in MS. Follow-up studies will address whether CSF parameters also predict long-term outcome in newly diagnosed CIS and MS patients.
Disclosure:
C. Gasperi: nothing to disclose.
A. Salmen has received speaker honoraria and/or travel compensation for activities with Almirall Hermal GmbH, Biogen, Merck, Novartis, Roche and Sanofi Genzyme, none related to this work.
G. Antony: nothing to disclose.
A. Bayas received personal compensation from Merck, Biogen, Bayer Vital, Novartis, TEVA, Roche and Sanofi/Genzyme and grants for congress trips and participation from Biogen, TEVA, Novartis, Sanofi/Genzyme and Merck.
T. Dankowski: nothing to disclose.
C. Heesen has received speaker honoraria and grants from Biogen, Genzyme, Roche and Merck.
T. Kümpfel has received travel expenses and personal compensations from Bayer Healthcare, Teva Pharma, Merck-Serono, Novartis, Sanofi-Aventis/Genzyme, Roche and Biogen as well as grant support from Bayer-Schering AG, Novartis and Chugai Pharma.
R.A. Linker received research support and/or personal compensation for activities with Bayer Health Care, Biogen, Genzyme/Sanofi, Merck, Novartis Pharma, Roche and TEVA Pharma.
F. Paul served on the steering committee for Novartis OCTIMS study and MedImmune; received speaker honoraria and travel funding from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, and MedImmune; is an academic editor for PLoS One; is an associate editor for Neurology®: Neuroimmunology & Neuroinflammation; has consulted for SanofiGenzyme, Biogen Idec, and MedImmune; and received research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research (BMBF Competence Network Multiple Sclerosis), and Arthur Arnstein Stiftung Berlin.
M. Stangel has received honoraria for scientific lectures or consultancy from Bayer Healthcare, Biogen, Baxter/Baxalta, CSL Behring, Euroimmune, Grifols, Merck-Serono, Novartis, Roche, Sanofi-Aventis, and Teva. His institution received research support from Bayer Healthcare, Biogen Idec, Genzyme, Merck-Serono, Novartis, and Teva.
B. Tackenberg received personal speaker honoraria and consultancy fees as a speaker and advisor from Bayer Healthcare, Biogen, CSL Behring, GRIFOLS, Merck Serono, Novartis, Octapharma, Roche, Sanofi Genzyme, TEVA und UCB Pharma. His University received unrestricted research grants from Biogen-idec, Novartis, TEVA, Bayer Healthcare, CSL-Behring, GRIFOLS, Octapharma, Sanofi Genzyme und UCB Pharma.
F. Then Bergh has no conflicts of interest with respect to the contents of this abstract. Within the past year before abstract submission, he received funding from the DFG; received, through his institution, research support for investigator-initiated studies from Actelion and Novartis; has served on scientific advisory boards for Novartis, Sanofi/Genzyme and Roche; has received support to attend a scientific meeting from Biogen; and has received personal honoraria for speaking from Bayer Schering, Biogen, Roche and Sanofi/Genzyme.
H. Tumani received speaker honoraria from Bayer, Biogen, Fresenius, Genzyme, Merck, Novartis, Roche, Siemens, Teva; serves as section editor for the Journal of Neurology, Psychiatry and Brain Research; and receives research support from Fresenius, Genzyme, Merck and Novartis, none related to this work.
C. Warnke received honoraria and/or research funding from Bayer, Biogen, Novartis and TEVA.
F. Weber received honoraria from Genzyme, Novartis TEVA and Biogen for speaking or for serving on a scientific advisory board, a travel grant for the attention of a scientific meeting from Merck-Serono and Novartis and grant support from Merck-Serono, Novartis and from the Federal Ministry of Education and Research (BMBF, Projects Biobanking and Omics in ControlMS as part of the Competence Network Multiple Sclerosis).
H. Wiendl receives honoraria for acting as a member of Scientific Advisory Boards and as consultant for Biogen, Evgen, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, as well as speaker honoraria and travel support from Alexion, Biogen, Cognomed, F. Hoffmann-La Roche Ltd., Gemeinnützige Hertie-Stiftung, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA, and WebMD Global. Prof. Wiendl is acting as a paid consultant for Abbvie, Actelion, Biogen, IGES, Novartis, Roche, Sanofi-Genzyme, and the Swiss Multiple Sclerosis Society. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Else Kröner Fresenius Foundation, Fresenius Foundation, Hertie Foundation, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies (IZKF) Muenster and RE Children's Foundation, Biogen GmbH, GlaxoSmithKline GmbH, Roche Pharma AG, Sanofi-Genzyme.
B. Wildemann received grants from the German Ministry of Education and Research, Dietmar Hopp Foundation and Klaus Tschira Foundation, grants and personal fees from Biogen, Merck Serono, Sanofi Genzyme, Novartis pharmaceuticals, Teva Pharma, and personal fees from Bayer Healthcare.
U.K. Zettl received no financial support for the research, authorship, and/or publication of this abstract.
U. Ziemann has received speaker honoraria and/or travel compensation from Biogen Idec GmbH, Bayer Vital GmbH, Bristol Myers Squibb GmbH, CorTec GmbH, Medtronic GmbH, and grants from Biogen Idec GmbH, Servier, and Janssen Pharmaceuticals NV, outside of the submitted work.
F. Zipp has received research grants from Teva, Merck Serono, Novartis and Bayer as well as consultation funds from Teva, Merck Serono, Novartis, Bayer Healthcare, Biogen Idec Germany, ONO, Genzyme, Sanofi-Aventis and Octapharma. Her travel compensation has been provided for by the aforementioned companies.
R. Gold received speaker's and board honoraria from Baxter, Bayer Schering, Biogen Idec, CLB Behring, Genzyme, Merck Serono, Novartis, Stendhal, Talecris, TEVA. His department received grant support from Bayer Schering, BiogenIdec, Genzyme, Merck Serono, Novartis, TEVA.
B. Hemmer has served on scientific advisory boards for F. Hoffmann-La Roche Ltd, Novartis, Bayer AG, and Genentech; he has served as DMSC member for AllergyCare; he or his institution have received speaker honoraria from Biogen Idec, Teva Neuroscience, Merck Serono, Medimmune, Novartis, Desitin, and F. Hoffmann-La Roche Ltd; his institution has received research support from Chugai Pharmaceuticals and Hoffmann-La-Roche; holds part of two patents; one for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon β.