Gasperi, Christiane, Salmen, Anke ORCID: 0000-0002-4751-299X, Antony, Gisela, Bayas, Antonios, Heesen, Christoph, Kuempfel, Tania, Linker, Ralf A., Paul, Friedemann, Stangel, Martin, Tackenberg, Bjoern, Bergh, Florian Then, Warnke, Clemens, Weber, Frank, Wiendl, Heinz, Wildemann, Brigitte, Zettl, Uwe K., Ziemann, Ulf, Zipp, Frauke, Tumani, Hayrettin, Gold, Ralf, Hemmer, Bernhard, Aktas, Orhan, Antony, Gisela, Ayzenberg, Ilya, Gold, Ralf, Hellwig, Kerstin, Salmen, Anke ORCID: 0000-0002-4751-299X, Lukas, Carsten, Bahn, Erik, Brueck, Wolfgang, Fluegel, Alexander, Friede, Tim, Lodygin, Dmitri, Meissner, Tina, Berger, Klaus, Buck, Dorothea, Hemmer, Bernhard, Muehlau, Mark, Korn, Thomas, Friese, Manuel, Heesen, Christoph, Stellmann, Jan-Patrick, Groppa, Sergiu, Luessi, Felix, Zipp, Frauke, Gross, Catharina, Klotz, Luisa, Meuth, Sven, Ruck, Tobias, Wiendl, Heinz, Haas, Juergen, Wildemann, Brigitte, Hohlfeld, Reinhard, Kerschensteiner, Martin, Kuempfel, Tania, Meinl, Edgar, Hohlfeld, Reinhard, Kerschensteiner, Martin, Korn, Thomas, Hemmer, Bernhard, Koenig, Inke, Kowarik, Markus, Ziemann, Ulf, Krishnamoorthy, Gurumoorthy ORCID: 0000-0002-7798-6707, Mueller-Myhsok, Bertram, Nischwitz, Sandra, Mueller-Myhsok, Bertram, Prinz, Marco, Salmen, Anke ORCID: 0000-0002-4751-299X, Stangel, Martin, Trebst, Corinna, Tumani, Hayrettin, Bayas, Antonios, Hartung, Hans-Peter, Linker, Ralf, Nischwitz, Sandra, Paul, Friedemann, Tackenberg, Bjoern, Bergh, Florian Then and Zettl, Uwe (2019). Association of Intrathecal Immunoglobulin G Synthesis With Disability Worsening in Multiple Sclerosis. JAMA Neurol., 76 (7). S. 841 - 850. CHICAGO: AMER MEDICAL ASSOC. ISSN 2168-6157

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Abstract

IMPORTANCE Reliable biomarkers associated with disability worsening in multiple sclerosis (MS) are still needed. OBJECTIVE To determine a possible association of intrathecal IgG synthesis and early disability worsening as measured by Expanded Disability Status Scale (EDSS) scoring in patients with relapsing-remitting MS or clinically isolated syndrome. DESIGN, SETTING, AND PARTICIPANTS Cerebrospinal fluid measurements and clinical data from the observational longitudinal German national multiple sclerosis cohort were analyzed. Patients were recruited between August 2010 and November 2015 from 18 centers. Data analysis was completed from August 2018 to December 2018. EXPOSURE Patients were offered standard immunotherapies per national treatment guidelines. MAIN OUTCOMES AND MEASURES A possible association between intrathecal IgG synthesis and risk of EDSS worsening 4 years after study inclusion was tested as the primary end point by multivariable binomial regression analysis. Kaplan-Meier analysis with a log-rank test was used to assess the association of intrathecal IgG synthesis with the time to EDSS worsening. Associations between intrathecal IgM or IgA synthesis and other cerebrospinal fluid parameters and EDSS worsening were analyzed as exploratory end points. Data collection began before the hypotheses were formulated. RESULTS Of all 1376 patients in the German Competence Network of Multiple Sclerosis cohort, 703 patients were excluded owing to missing cerebrospinal fluid or EDSS data. Of the 673 included patients, 459 (68.2%) were women. The mean (SD) age at baseline was 34 (10) years. Intrathecal IgG synthesis was associated with a higher risk of EDSS worsening after 4 years (odds ratio, 2.02 [95% CI, 1.15-3.58]; P=.01), independent of the occurrence of relapses and disease-modifying therapy. Additionally, intrathecal IgG synthesis was associated with earlier EDSS worsening; 4 years after study entry, worsening occurred in 28.4% (95% CI, 22.7%-34.1%) and 18.1% (95% CI, 12.4%-23.9%) of patients with and without intrathecal IgG synthesis, respectively. No association of other routine cerebrospinal fluid parameters with EDSS worsening was found. CONCLUSIONS AND RELEVANCE Patients with new diagnoses of relapsing-remitting multiple sclerosis or clinically isolated syndrome with intrathecal IgG synthesis had a higher risk of and shorter time to EDSS worsening across a 4-year period of follow-up. Intrathecal IgG synthesis is a potentially useful marker for disability worsening in patients with multiple sclerosis and may be useful for early treatment decisions.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gasperi, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salmen, AnkeUNSPECIFIEDorcid.org/0000-0002-4751-299XUNSPECIFIED
Antony, GiselaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bayas, AntoniosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heesen, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuempfel, TaniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linker, Ralf A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paul, FriedemannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stangel, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tackenberg, BjoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergh, Florian ThenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Warnke, ClemensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiendl, HeinzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wildemann, BrigitteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zettl, Uwe K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziemann, UlfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zipp, FraukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tumani, HayrettinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gold, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hemmer, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aktas, OrhanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antony, GiselaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ayzenberg, IlyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gold, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hellwig, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salmen, AnkeUNSPECIFIEDorcid.org/0000-0002-4751-299XUNSPECIFIED
Lukas, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bahn, ErikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brueck, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fluegel, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friede, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lodygin, DmitriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meissner, TinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berger, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buck, DorotheaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hemmer, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muehlau, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korn, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friese, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heesen, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stellmann, Jan-PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Groppa, SergiuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luessi, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zipp, FraukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gross, CatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klotz, LuisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meuth, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruck, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiendl, HeinzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haas, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wildemann, BrigitteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hohlfeld, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kerschensteiner, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuempfel, TaniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meinl, EdgarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hohlfeld, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kerschensteiner, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korn, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hemmer, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenig, InkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kowarik, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziemann, UlfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krishnamoorthy, GurumoorthyUNSPECIFIEDorcid.org/0000-0002-7798-6707UNSPECIFIED
Mueller-Myhsok, BertramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nischwitz, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller-Myhsok, BertramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prinz, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salmen, AnkeUNSPECIFIEDorcid.org/0000-0002-4751-299XUNSPECIFIED
Stangel, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trebst, CorinnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tumani, HayrettinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bayas, AntoniosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartung, Hans-PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linker, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nischwitz, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paul, FriedemannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tackenberg, BjoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergh, Florian ThenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zettl, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-135821
DOI: 10.1001/jamaneurol.2019.0905
Journal or Publication Title: JAMA Neurol.
Volume: 76
Number: 7
Page Range: S. 841 - 850
Date: 2019
Publisher: AMER MEDICAL ASSOC
Place of Publication: CHICAGO
ISSN: 2168-6157
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CEREBROSPINAL-FLUID ANALYSIS; PROGNOSTIC VALUE; NATURAL-HISTORY; OLIGOCLONAL IGM; DISEASE COURSE; PROGRESSION; DIAGNOSIS; CONVERSION; PREDICTS; BANDSMultiple languages
Clinical NeurologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13582

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