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31 results on '"Tackenberg, Bjoern"'

1. Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity

Author

German Competence Network Multiple Sclerosis (KKNMS) and the BIONAT Network, Ostkamp, Patrick, Salmen, Anke, Pignolet, Béatrice, Görlich, Dennis, Andlauer, Till F. M., Schulte-Mecklenbeck, Andreas, Gonzalez-Escamilla, Gabriel, Bucciarelli, Florence, Gennero, Isabelle, Breuer, Johanna, Antony, Gisela, Schneider-Hohendorf, Tilman, Mykicki, Nadine, Bayas, Antonios, Bergh, Florian Then, Bittner, Stefan, Hartung, Hans-Peter, Friese, Manuel A., Linker, Ralf A., Luessi, Felix, Lehmann-Horn, Klaus, Mühlau, Mark, Paul, Friedemann, Stangel, Martin, Tackenberg, Björn, Tumani, Hayrettin, Warnke, Clemens, Weber, Frank, Wildemann, Brigitte, Zettl, Uwe K., Ziemann, Ulf, Müller-Myhsok, Bertram, Kümpfel, Tania, Klotz, Luisa, Meuth, Sven G., Zipp, Frauke, Hemmer, Bernhard, Hohlfeld, Reinhard, Brassat, David, Gold, Ralf, Gross, Catharina C., Lukas, Carsten, Groppa, Sergiu, Loser, Karin, Wiendl, Heinz, and Schwab, Nicholas

Published
2021

3. Clinical implications of serum neurofilament in newly diagnosed MS patients: A longitudinal multicentre cohort study

Author

Bittner, Stefan, Steffen, Falk, Uphaus, Timo, Muthuraman, Muthuraman, Fleischer, Vinzenz, Salmen, Anke, Luessi, Felix, Berthele, Achim, Klotz, Luisa, Meuth, Sven G., Bayas, Antonios, Paul, Friedemann, Hartung, Hans-Peter, Linker, Ralf, Heesen, Christoph, Stangel, Martin, Wildemann, Brigitte, Then Bergh, Florian, Tackenberg, Björn, Kuempfel, Tania, Weber, Frank, Zettl, Uwe K., Ziemann, Ulf, Tumani, Hayrettin, Groppa, Sergiu, Mühlau, Mark, Lukas, Carsten, Hemmer, Bernhard, Wiendl, Heinz, Gold, Ralf, and Zipp, Frauke

Published
2020
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5. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Author

Mitrovič, Mitja, Patsopoulos, Nikolaos A., Beecham, Ashley H., Dankowski, Theresa, Goris, An, Dubois, Bénédicte, D’hooghe, Marie B., Lemmens, Robin, Van Damme, Philip, Søndergaard, Helle Bach, Sellebjerg, Finn, Sorensen, Per Soelberg, Ullum, Henrik, Thørner, Lise W., Werge, Thomas, Saarela, Janna, Cournu-Rebeix, Isabelle, Damotte, Vincent, Fontaine, Bertrand, Guillot-Noel, Lena, Lathrop, Mark, Vukusik, Sandra, Gourraud, Pierre-Antoine, Andlauer, Till F.M., Pongratz, Viola, Buck, Dorothea, Gasperi, Christiane, Bayas, Antonios, Heesen, Christoph, Kümpfel, Tania, Linker, Ralf, Paul, Friedemann, Stangel, Martin, Tackenberg, Björn, Bergh, Florian Then, Warnke, Clemens, Wiendl, Heinz, Wildemann, Brigitte, Zettl, Uwe, Ziemann, Ulf, Tumani, Hayrettin, Gold, Ralf, Grummel, Verena, Hemmer, Bernhard, Knier, Benjamin, Lill, Christina M., Luessi, Felix, Dardiotis, Efthimios, Agliardi, Cristina, Barizzone, Nadia, Mascia, Elisabetta, Bernardinelli, Luisa, Comi, Giancarlo, Cusi, Daniele, Esposito, Federica, Ferrè, Laura, Comi, Cristoforo, Galimberti, Daniela, Leone, Maurizio A., Sorosina, Melissa, Mescheriakova, Julia, Hintzen, Rogier, van Duijn, Cornelia, Teunissen, Charlotte E., Bos, Steffan D., Myhr, Kjell-Morten, Celius, Elisabeth G., Lie, Benedicte A., Spurkland, Anne, Comabella, Manuel, Montalban, Xavier, Alfredsson, Lars, Stridh, Pernilla, Hillert, Jan, Jagodic, Maja, Piehl, Fredrik, Jelčić, Ilijas, Martin, Roland, Sospedra, Mireia, Ban, Maria, Hawkins, Clive, Hysi, Pirro, Kalra, Seema, Karpe, Fredrik, Khadake, Jyoti, Lachance, Genevieve, Neville, Matthew, Santaniello, Adam, Caillier, Stacy J., Calabresi, Peter A., Cree, Bruce A.C., Cross, Anne, Davis, Mary F., Haines, Jonathan L., de Bakker, Paul I.W., Delgado, Silvia, Dembele, Marieme, Edwards, Keith, Fitzgerald, Kathryn C., Hakonarson, Hakon, Konidari, Ioanna, Lathi, Ellen, Manrique, Clara P., Pericak-Vance, Margaret A., Piccio, Laura, Schaefer, Cathy, McCabe, Cristin, Weiner, Howard, Goldstein, Jacqueline, Olsson, Tomas, Hadjigeorgiou, Georgios, Taylor, Bruce, Tajouri, Lotti, Charlesworth, Jac, Booth, David R., Harbo, Hanne F., Ivinson, Adrian J., Hauser, Stephen L., Compston, Alastair, Stewart, Graeme, Zipp, Frauke, Barcellos, Lisa F., Baranzini, Sergio E., Martinelli-Boneschi, Filippo, D’Alfonso, Sandra, Ziegler, Andreas, Oturai, Annette, McCauley, Jacob L., Sawcer, Stephen J., Oksenberg, Jorge R., De Jager, Philip L., Kockum, Ingrid, Hafler, David A., and Cotsapas, Chris

Published
2018
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11. Cytokines and epilepsy

Author

Li, Gang, Bauer, Sebastian, Nowak, Mareike, Norwood, Braxton, Tackenberg, Björn, Rosenow, Felix, Knake, Susanne, Oertel, Wolfgang H., and Hamer, Hajo M.

Published
2011
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14. Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis

Author

Abrahamyan, Sargis, Eberspaecher, Bettina, Hoshi, Muna-Miriam, Aly, Lilian, Luessi, Felix, Groppa, Sergiu, Klotz, Luisa, Meuth, Sven G., Schroeder, Christoph, Grueter, Thomas, Tackenberg, Bjoern, Paul, Friedemann, Then-Bergh, Florian, Kuempfel, Tania, Weber, Frank, Stangel, Martin, Bayas, Antonios, Wildemann, Brigitte, Heesen, Christoph, Zettl, Uwe, Warnke, Clemens, Antony, Gisela, Hessler, Nicole, Wiendl, Heinz, Bittner, Stefan, Hemmer, Bernhard, Gold, Ralf, Salmen, Anke, Ruprecht, Klemens, Abrahamyan, Sargis, Eberspaecher, Bettina, Hoshi, Muna-Miriam, Aly, Lilian, Luessi, Felix, Groppa, Sergiu, Klotz, Luisa, Meuth, Sven G., Schroeder, Christoph, Grueter, Thomas, Tackenberg, Bjoern, Paul, Friedemann, Then-Bergh, Florian, Kuempfel, Tania, Weber, Frank, Stangel, Martin, Bayas, Antonios, Wildemann, Brigitte, Heesen, Christoph, Zettl, Uwe, Warnke, Clemens, Antony, Gisela, Hessler, Nicole, Wiendl, Heinz, Bittner, Stefan, Hemmer, Bernhard, Gold, Ralf, Salmen, Anke, and Ruprecht, Klemens

Abstract

Objective To determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS). Methods Serum samples were collected from 901 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting multiple sclerosis (RRMS) participating in the German National MS cohort, a prospective cohort of patients with early MS with stringent inclusion criteria. Epstein-Barr nuclear antigen (EBNA)-1 and viral capsid antigen (VCA) antibodies were measured in diluted sera by chemiluminescence immunoassays (CLIAs). Sera of EBNA-1 and VCA antibody-negative patients were retested undiluted by an EBV IgG immunoblot. For comparison, we retrospectively analysed the EBV seroprevalence across different age cohorts, ranging from 0 to >80 years, in a large hospital population (N=16 163) from Berlin/Northern Germany. Results EBNA-1 antibodies were detected by CLIA in 839 of 901 patients with CIS/RRMS. Of the 62 patients without EBNA-1 antibodies, 45 had antibodies to VCA as detected by CLIA. In all of the remaining 17 patients, antibodies to EBV were detected by immunoblot. Altogether, 901 of 901 (100%) patients with CIS/RRMS were EBV-seropositive. EBV seropositivity increased with age in the hospital population but did not reach 100% in any of the investigated age cohorts. Conclusion The complete EBV seropositivity in this large cohort of patients with early MS strengthens the evidence for a role of EBV in MS. It also suggests that a negative EBV serology in patients with suspected inflammatory central nervous system disease should alert clinicians to consider diagnoses other than MS.

Published
2020

15. Genetic determinants of the humoral immune response in MS

Author

Gasperi, Christiane, Andlauer, Till F. M., Keating, Ana, Knier, Benjamin, Klein, Ana, Pernpeintner, Verena, Lichtner, Peter, Gold, Ralf, Zipp, Frauke, Bergh, Florian Then, Stangel, Martin, Tumani, Hayrettin, Wildemann, Brigitte, Wiendl, Heinz, Bayas, Antonios, Kuempfel, Tania, Zettl, Uwe K., Linker, Ralf A., Ziemann, Ulf, Knop, Matthias, Warnke, Clemens, Friese, Manuel A., Paul, Friedemann, Tackenberg, Bjoern, Berthele, Achim, Hemmer, Bernhard, Gasperi, Christiane, Andlauer, Till F. M., Keating, Ana, Knier, Benjamin, Klein, Ana, Pernpeintner, Verena, Lichtner, Peter, Gold, Ralf, Zipp, Frauke, Bergh, Florian Then, Stangel, Martin, Tumani, Hayrettin, Wildemann, Brigitte, Wiendl, Heinz, Bayas, Antonios, Kuempfel, Tania, Zettl, Uwe K., Linker, Ralf A., Ziemann, Ulf, Knop, Matthias, Warnke, Clemens, Friese, Manuel A., Paul, Friedemann, Tackenberg, Bjoern, Berthele, Achim, and Hemmer, Bernhard

Abstract

Objective In this observational study, we investigated the impact of genetic factors at the immunoglobulin heavy chain constant locus on chromosome 14 and the major histocompatibility complex region on intrathecal immunoglobulin G, A, and M levels as well as on B cells and plasmablasts in the CSF and blood of patients with multiple sclerosis (MS). Methods Using regression analyses, we tested genetic variants on chromosome 14 and imputed human leukocyte antigen (HLA) alleles for associations with intrathecal immunoglobulins in 1,279 patients with MS or clinically isolated syndrome and with blood and CSF B cells and plasmablasts in 301 and 348 patients, respectively. Results The minor alleles of variants on chromosome 14 were associated with higher intrathecal immunoglobulin G levels (beta = 0.58 [0.47 to 0.68], lowest adjusted p = 2.32 x 10(-23)), and lower intrathecal immunoglobulin M (beta = -0.56 [-0.67 to -0.46], p = 2.06 x 10(-24)) and A (beta = -0.42 [-0.54 to -0.31], p = 7.48 x 10(-11)) levels. Alleles from the HLA-B*07:02-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype were associated with higher (lowest p = 2.14 x 10(-7)) and HLA-B*44:02 with lower (beta = -0.35 [-0.54 to -0.17], p = 1.38 x 10(-2)) immunoglobulin G levels. Of interest, different HLA alleles were associated with lower intrathecal immunoglobulin M (HLA-C*02:02, beta = -0.45 [-0.61 to -0.28], p = 1.01 x 10(-5)) and higher immunoglobulin A levels (HLA-DQA1*01:03-DQB1*06:03-DRB1*13:01 haplotype, beta = 0.40 [0.21 to 0.60], p = 4.46 x 10(-3)). The impact of HLA alleles on intrathecal immunoglobulin G and M levels could mostly be explained by associations with CSF B cells and plasmablasts. Conclusion Although some HLA alleles seem to primarily drive the extent of humoral immune responses in the CNS by increasing CSF B cells and plasmablasts, genetic variants at the immunoglobulin heavy chain constant locus might regulate intrathecal immunoglobulins levels via different mechanisms.

Published
2020

16. Can we predict cognitive decline after initial diagnosis of multiple sclerosis? Results from the German National early MS cohort (KKNMS)

Author

Johnen, Andreas, Buerkner, Paul-Christian, Landmeyer, Nils C., Ambrosius, Bjoern, Calabrese, Pasquale, Motte, Jeremias, Hessler, Nicole, Antony, Gisela, Koenig, Inke R., Klotz, Luisa, Hoshi, Muna-Miriam, Aly, Lilian, Groppa, Sergiu, Luessi, Felix, Paul, Friedemann, Tackenberg, Bjoern, Bergh, Florian Then, Kuempfel, Tania, Tumani, Hayrettin, Stangel, Martin, Weber, Frank, Bayas, Antonios, Wildemann, Brigitte, Heesen, Christoph, Zettl, Uwe K., Zipp, Frauke, Hemmer, Bernhard, Meuth, Sven G., Gold, Ralf, Wiendl, Heinz, Salmen, Anke, Demir, Seray, Schroeder, Christoph, Voithenleitner, Lisa A., Berthele, Achim, Haars, Sarah, Nischwitz, Sandra, Knop, Matthias J., Rothacher, Susanne, Poettgen, Jana, Warnke, Clemens, Linker, Ralf A., Ziemann, Ulf, Johnen, Andreas, Buerkner, Paul-Christian, Landmeyer, Nils C., Ambrosius, Bjoern, Calabrese, Pasquale, Motte, Jeremias, Hessler, Nicole, Antony, Gisela, Koenig, Inke R., Klotz, Luisa, Hoshi, Muna-Miriam, Aly, Lilian, Groppa, Sergiu, Luessi, Felix, Paul, Friedemann, Tackenberg, Bjoern, Bergh, Florian Then, Kuempfel, Tania, Tumani, Hayrettin, Stangel, Martin, Weber, Frank, Bayas, Antonios, Wildemann, Brigitte, Heesen, Christoph, Zettl, Uwe K., Zipp, Frauke, Hemmer, Bernhard, Meuth, Sven G., Gold, Ralf, Wiendl, Heinz, Salmen, Anke, Demir, Seray, Schroeder, Christoph, Voithenleitner, Lisa A., Berthele, Achim, Haars, Sarah, Nischwitz, Sandra, Knop, Matthias J., Rothacher, Susanne, Poettgen, Jana, Warnke, Clemens, Linker, Ralf A., and Ziemann, Ulf

Abstract

BackgroundCognitive impairment (CI) affects approximately one-third of the patients with early multiple sclerosis (MS) and clinically isolated syndrome (CIS). Little is known about factors predicting CI and progression after initial diagnosis.MethodsNeuropsychological screening data from baseline and 1-year follow-up of a prospective multicenter cohort study (NationMS) involving 1123 patients with newly diagnosed MS or CIS were analyzed. Employing linear multilevel models, we investigated whether demographic, clinical and conventional MRI markers at baseline were predictive for CI and longitudinal cognitive changes.ResultsAt baseline, 22% of patients had CI (impairment in 2 cognitive domains) with highest frequencies and severity in processing speed and executive functions. Demographics (fewer years of academic education, higher age, male sex), clinical (EDSS, depressive symptoms) but no conventional MRI characteristics were linked to baseline CI. At follow-up, only 14% of patients showed CI suggesting effects of retesting. Neither baseline characteristics nor initiation of treatment between baseline and follow-up was able to predict cognitive changes within the follow-up period of 1 year.ConclusionsIdentification of risk factors for short-term cognitive change in newly diagnosed MS or CIS is insufficient using only demographic, clinical and conventional MRI data. Change-sensitive, re-test reliable cognitive tests and more sophisticated predictors need to be employed in future clinical trials and cohort studies of early-stage MS to improve prediction.

Published
2019

17. Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies

Author

Merkies, Ingemar S. J., van Schaik, Ivo N., Leger, Jean-Marc, Bril, Vera, van Geloven, Nan, Hartung, Hans-Peter, Lewis, Richard A., Sobue, Gen, Lawo, John-Philip, Durn, Billie L., Cornblath, David R., De Bleecker, Jan L., Sommer, Claudia, Robberecht, Wim, Saarela, Mika, Kamienowski, Jerzy, Stelmasiak, Zbigniew, Tackenberg, Bjoern, Mielke, Orell, Sabet, A., George, K., Roberts, L., Carne, R., Blum, S., Henderson, R., Van Damme, P., Demeestere, J., Larue, S., D'Amour, C., Kunc, P., Valis, M., Sussova, J., Kalous, T., Talab, R., Bednar, M., Toomsoo, T., Rubanovits, I., Gross-Paju, K., Sorro, U., Saarela, M., Auranen, M., Pouget, J., Attarian, S., Le Masson, G., Wielanek-Bachelet, A., Desnuelle, C., Delmont, E., Clavelou, P., Aufauvre, D., Schmidt, J., Zschuentzsch, J., Sommer, C., Kramer, D., Hoffmann, O., Goerlitz, C., Haas, J., Chatzopoulos, M., Yoon, R., Gold, R., Berlit, P., Jaspert-Grehl, A., Liebetanz, D., Kutschenko, A., Stangel, M., Trebst, C., Baum, P., Bergh, F., Klehmet, J., Meisel, A., Klostermann, F., Oechtering, J., Lehmann, H., Schroeter, M., Hagenacker, T., Mueller, D., Sperfeld, A., Bethke, F., Drory, V., Algom, A., Yarnitsky, D., Murinson, B., Di Muzio, A., Ciccocioppo, F., Sorbi, S., Mata, S., Schenone, A., Grandis, M., Lauria, G., Cazzato, D., Antonini, G., Morino, S., Cocito, D., Zibetti, M., Yokota, T., Ohkubo, T., Kanda, T., Kawai, M., Kaida, K., Onoue, H., Kuwabara, S., Mori, M., Iijima, M., Ohyama, K., Baba, M., Tomiyama, M., Nishiyama, K., Akutsu, T., Yokoyama, K., Kanai, K., van Schaik, I. N., Eftimov, F., Notermans, N. C., Visser, N., Faber, C., Hoeijmakers, J., Rejdak, K., Chyrchel-Paszkiewicz, U., Casanovas Pons, C., Antonia, M., Gamez, J., Salvado, M., Marquez Infante, C., Benitez, S., Lunn, M., Morrow, J., Gosal, D., Lavin, T., Melamed, I., Testori, A., Ajroud-Driss, S., Menichella, D., Lai, E. Chi-Ho, Dimachkie, M., Barohn, R. J., Beydoun, S., Johl, H., Lange, D., Shtilbans, A., Muley, S., Ladha, S., Freimer, M., Kissel, J., Latov, N., Chin, R., Ubogu, E., Mumfrey, S., Rao, T., MacDonald, P., Sharma, K., Gonzalez, G., Allen, J., Walk, D., Hobson-Webb, L., Gable, K., De Bleecker, J. L., Franques, J., Leger, J. -M., Morales, R. Juntas, Nguento, A., Schrey, Ch., Kamienowski, J., Stelmasiak, Z., Zwolinska, G., Merkies, Ingemar S. J., van Schaik, Ivo N., Leger, Jean-Marc, Bril, Vera, van Geloven, Nan, Hartung, Hans-Peter, Lewis, Richard A., Sobue, Gen, Lawo, John-Philip, Durn, Billie L., Cornblath, David R., De Bleecker, Jan L., Sommer, Claudia, Robberecht, Wim, Saarela, Mika, Kamienowski, Jerzy, Stelmasiak, Zbigniew, Tackenberg, Bjoern, Mielke, Orell, Sabet, A., George, K., Roberts, L., Carne, R., Blum, S., Henderson, R., Van Damme, P., Demeestere, J., Larue, S., D'Amour, C., Kunc, P., Valis, M., Sussova, J., Kalous, T., Talab, R., Bednar, M., Toomsoo, T., Rubanovits, I., Gross-Paju, K., Sorro, U., Saarela, M., Auranen, M., Pouget, J., Attarian, S., Le Masson, G., Wielanek-Bachelet, A., Desnuelle, C., Delmont, E., Clavelou, P., Aufauvre, D., Schmidt, J., Zschuentzsch, J., Sommer, C., Kramer, D., Hoffmann, O., Goerlitz, C., Haas, J., Chatzopoulos, M., Yoon, R., Gold, R., Berlit, P., Jaspert-Grehl, A., Liebetanz, D., Kutschenko, A., Stangel, M., Trebst, C., Baum, P., Bergh, F., Klehmet, J., Meisel, A., Klostermann, F., Oechtering, J., Lehmann, H., Schroeter, M., Hagenacker, T., Mueller, D., Sperfeld, A., Bethke, F., Drory, V., Algom, A., Yarnitsky, D., Murinson, B., Di Muzio, A., Ciccocioppo, F., Sorbi, S., Mata, S., Schenone, A., Grandis, M., Lauria, G., Cazzato, D., Antonini, G., Morino, S., Cocito, D., Zibetti, M., Yokota, T., Ohkubo, T., Kanda, T., Kawai, M., Kaida, K., Onoue, H., Kuwabara, S., Mori, M., Iijima, M., Ohyama, K., Baba, M., Tomiyama, M., Nishiyama, K., Akutsu, T., Yokoyama, K., Kanai, K., van Schaik, I. N., Eftimov, F., Notermans, N. C., Visser, N., Faber, C., Hoeijmakers, J., Rejdak, K., Chyrchel-Paszkiewicz, U., Casanovas Pons, C., Antonia, M., Gamez, J., Salvado, M., Marquez Infante, C., Benitez, S., Lunn, M., Morrow, J., Gosal, D., Lavin, T., Melamed, I., Testori, A., Ajroud-Driss, S., Menichella, D., Lai, E. Chi-Ho, Dimachkie, M., Barohn, R. J., Beydoun, S., Johl, H., Lange, D., Shtilbans, A., Muley, S., Ladha, S., Freimer, M., Kissel, J., Latov, N., Chin, R., Ubogu, E., Mumfrey, S., Rao, T., MacDonald, P., Sharma, K., Gonzalez, G., Allen, J., Walk, D., Hobson-Webb, L., Gable, K., De Bleecker, J. L., Franques, J., Leger, J. -M., Morales, R. Juntas, Nguento, A., Schrey, Ch., Kamienowski, J., Stelmasiak, Z., and Zwolinska, G.

Abstract

Intravenous immunoglobulin (IVIG) is a potential therapy for chronic inflammatory demyelinating polyneuropathy (CIDP). To investigate the efficacy and safety of the IVIG IgPro10 (Privigen) for treatment of CIDP, results from Privigen Impact on Mobility and Autonomy (PRIMA), a prospective, open-label, single-arm study of IVIG in immunoglobulin (Ig)-naive or IVIG pre-treated subjects (NCT01184846, n = 28) and Polyneuropathy And Treatment with Hizentra (PATH), a double-blind, randomized study including an open-label, single-arm IVIG phase in IVIG pre-treated subjects (NCT01545076, IVIG restabilization phase n = 207) were analyzed separately and together (n = 235). Efficacy assessments included change in adjusted inflammatory neuropathy cause and treatment (INCAT) score, grip strength and Medical Research Council (MRC) sum score. Adverse drug reactions (ADRs) and ADRs/infusion were recorded. Adjusted INCAT response rate was 60.7% in all PRIMA subjects at Week 25 (76.9% in IVIG pre-treated subjects) and 72.9% in PATH. In the pooled cohort (n = 235), INCAT response rate was 71.5%; median time to INCAT improvement was 4.3 weeks. No clear demographic differences were noticed between early (responding before Week 7, n = 148) and late responders (n = 21). In the pooled cohort, median change from baseline to last observation was -1.0 (interquartile range -2.0; 0.0) point for INCAT score; +8.0 (0.0; 20.0) kPa for maximum grip strength; +3.0 (1.0; 7.0) points for MRC sum score. In the pooled cohort, 271 ADRs were reported in 105 subjects (44.7%), a rate of 0.144 ADRs per infusion. This analysis confirms the efficacy and safety of IgPro10, a recently FDA-approved IVIG for CIDP, in a population of mainly pre-treated subjects with CIDP [Correction added on 14 March 2019 after first online publication: the INCAT response rate has been corrected.].

Published
2019

18. Efficacy and safety of alemtuzumab versus fingolimod in RRMS after natalizumab cessation

Author

Pfeuffer, Steffen, Schmidt, Rene, Straeten, Frederike Anne, Pul, Refik, Kleinschnitz, Christoph, Wieshuber, Marinus, Lee, De-Hyung, Linker, Ralf A., Doerck, Sebastian, Straeten, Vera, Windhagen, Susanne, Pawlitzki, Marc, Aufenberg, Christoph, Lang, Michael, Eienbroeker, Christian, Tackenberg, Bjoern, Limmroth, Volker, Wildemann, Brigitte, Haas, Juergen, Klotz, Luisa, Wiendl, Heinz, Ruck, Tobias, Meuth, Sven G., Pfeuffer, Steffen, Schmidt, Rene, Straeten, Frederike Anne, Pul, Refik, Kleinschnitz, Christoph, Wieshuber, Marinus, Lee, De-Hyung, Linker, Ralf A., Doerck, Sebastian, Straeten, Vera, Windhagen, Susanne, Pawlitzki, Marc, Aufenberg, Christoph, Lang, Michael, Eienbroeker, Christian, Tackenberg, Bjoern, Limmroth, Volker, Wildemann, Brigitte, Haas, Juergen, Klotz, Luisa, Wiendl, Heinz, Ruck, Tobias, and Meuth, Sven G.

Abstract

BackgroundNatalizumab (NTZ) was the first approved monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite proven and sustained efficacy, its use is limited by the risk of progressive multifocal leukoencephalopathy (PML). Moreover, some patients show ongoing disease activity under NTZ, requiring a switch to another disease-modifying treatment (DMT). However, evidence regarding the optimal DMT for treatment of active RRMS after NTZ-cessation is still scarce.ObjectiveTo evaluate efficacy and safety outcomes of ALEM vs FTY treatment after cessation of NTZ.MethodsWe retrospectively identified patients at 12 German neurology centers and analyzed risks for disease activity, adverse events, disability progression, and treatment discontinuation.Results195 patients were identified and 144 underwent final analysis (FTY: 101; ALEM: 42). The hazard ratio for clinical relapses was 2.24 favoring ALEM (95% CI 1.12-4.50; p=0.015). The hazard ratio for adverse events was 7.78 (95% CI 1.04-57.95; p=0.006) and 2.41 for MRI progression (95% CI 1.26-4.60; p=0.004). The odds ratio for disability progression after 12months was 4.84 (95% CI 1.74-13.47, p=0.003). Differences remained after adjusting for possible confounders (e.g., age, sex, baseline disability, NTZ treatment duration, washout time).ConclusionOur findings indicated particular advantages of ALEM compared to FTY in patients stopping NTZ.

Published
2019

19. Association of Intrathecal Immunoglobulin G Synthesis With Disability Worsening in Multiple Sclerosis

Author

Gasperi, Christiane, Salmen, Anke, 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, Ayzenberg, Ilya, Hellwig, Kerstin, Lukas, Carsten, Bahn, Erik, Brueck, Wolfgang, Fluegel, Alexander, Friede, Tim, Lodygin, Dmitri, Meissner, Tina, Berger, Klaus, Buck, Dorothea, Muehlau, Mark, Korn, Thomas, Friese, Manuel, Stellmann, Jan-Patrick, Groppa, Sergiu, Luessi, Felix, Gross, Catharina, Klotz, Luisa, Meuth, Sven, Ruck, Tobias, Haas, Juergen, Hohlfeld, Reinhard, Kerschensteiner, Martin, Meinl, Edgar, Koenig, Inke, Kowarik, Markus, Krishnamoorthy, Gurumoorthy, Mueller-Myhsok, Bertram, Nischwitz, Sandra, Prinz, Marco, Trebst, Corinna, Hartung, Hans-Peter, Linker, Ralf, Zettl, Uwe, Gasperi, Christiane, Salmen, Anke, 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, Ayzenberg, Ilya, Hellwig, Kerstin, Lukas, Carsten, Bahn, Erik, Brueck, Wolfgang, Fluegel, Alexander, Friede, Tim, Lodygin, Dmitri, Meissner, Tina, Berger, Klaus, Buck, Dorothea, Muehlau, Mark, Korn, Thomas, Friese, Manuel, Stellmann, Jan-Patrick, Groppa, Sergiu, Luessi, Felix, Gross, Catharina, Klotz, Luisa, Meuth, Sven, Ruck, Tobias, Haas, Juergen, Hohlfeld, Reinhard, Kerschensteiner, Martin, Meinl, Edgar, Koenig, Inke, Kowarik, Markus, Krishnamoorthy, Gurumoorthy, Mueller-Myhsok, Bertram, Nischwitz, Sandra, Prinz, Marco, Trebst, Corinna, Hartung, Hans-Peter, Linker, Ralf, and Zettl, Uwe

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

Published
2019

20. Diagnostics and treatment of tuberculosis under immunotherapy for multiple sclerosis. Current status and recommendations in Germany

Author

Bittner, Stefan, Engel, Sinah, Lange, Christoph, Weber, Martin S., Haghikia, Aiden, Luessi, Felix, Korn, Thomas, Klotz, Luisa, Bayas, Antonios, Paul, Friedemann, Heesen, Christoph, Stangel, Martin, Wildemann, Brigitte, Bergh, Florian Then, Tackenberg, Bjoern, Trebst, Corinna, Warnke, Clemens, Linker, Ralf, Kerschensteiner, Martin, Zettl, Uwe, Tumani, Hayrettin, Brueck, Wolfgang, Meuth, Sven G., Kuempfel, Tanja, Hemmer, Bernhard, Wiendl, Heinz, Gold, Ralf, Zipp, Frauke, Bittner, Stefan, Engel, Sinah, Lange, Christoph, Weber, Martin S., Haghikia, Aiden, Luessi, Felix, Korn, Thomas, Klotz, Luisa, Bayas, Antonios, Paul, Friedemann, Heesen, Christoph, Stangel, Martin, Wildemann, Brigitte, Bergh, Florian Then, Tackenberg, Bjoern, Trebst, Corinna, Warnke, Clemens, Linker, Ralf, Kerschensteiner, Martin, Zettl, Uwe, Tumani, Hayrettin, Brueck, Wolfgang, Meuth, Sven G., Kuempfel, Tanja, Hemmer, Bernhard, Wiendl, Heinz, Gold, Ralf, and Zipp, Frauke

Abstract

After years of low incidence, a large increase of new tuberculosis (TB) cases has been reported in Germany since 2015. New immunotherapies for the treatment of multiple sclerosis (MS) are associated with a reduced immune competence and a potential increased risk for infections. Most neurologists lack specific experiences with TB infections. This article summarizes specific recommendations for the diagnostics and treatment of TB under MS immunotherapies with a focus on the situation in Germany. Due to low case numbers and little experience with the risk of TB under the new immunotherapies, the clinical competence network for MS (KKNMS) consensus recommendations have a low grade of evidence.

Published
2019

21. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Author

Mitrovič, Mitja, Patsopoulos, Nikolaos A., Beecham, Ashley H., Dankowski, Theresa, Goris, An, Dubois, Bénédicte, D’hooghe, Marie B., Lemmens, Robin, Van Damme, Philip, Søndergaard, Helle Bach, Sellebjerg, Finn, Sorensen, Per Soelberg, Ullum, Henrik, Thørner, Lise W., Werge, Thomas, Saarela, Janna, Cournu-Rebeix, Isabelle, Damotte, Vincent, Fontaine, Bertrand, Guillot-Noel, Lena, Lathrop, Mark, Vukusik, Sandra, Gourraud, Pierre-Antoine, Andlauer, Till F.M., Pongratz, Viola, Buck, Dorothea, Gasperi, Christiane, Bayas, Antonios, Heesen, Christoph, Kümpfel, Tania, Linker, Ralf, Paul, Friedemann, Stangel, Martin, Tackenberg, Björn, Bergh, Florian Then, Warnke, Clemens, Wiendl, Heinz, Wildemann, Brigitte, Zettl, Uwe, Ziemann, Ulf, Tumani, Hayrettin, Gold, Ralf, Grummel, Verena, Hemmer, Bernhard, Knier, Benjamin, Lill, Christina M., Luessi, Felix, Dardiotis, Efthimios, Agliardi, Cristina, Barizzone, Nadia, Mascia, Elisabetta, Bernardinelli, Luisa, Comi, Giancarlo, Cusi, Daniele, Esposito, Federica, Ferrè, Laura, Comi, Cristoforo, Galimberti, Daniela, Leone, Maurizio A., Sorosina, Melissa, Mescheriakova, Julia, Hintzen, Rogier, van Duijn, Cornelia, Teunissen, Charlotte E., Bos, Steffan D., Myhr, Kjell-Morten, Celius, Elisabeth G., Lie, Benedicte A., Spurkland, Anne, Comabella, Manuel, Montalban, Xavier, Alfredsson, Lars, Stridh, Pernilla, Hillert, Jan, Jagodic, Maja, Piehl, Fredrik, Jelčić, Ilijas, Martin, Roland, Sospedra, Mireia, Ban, Maria, Hawkins, Clive, Hysi, Pirro, Kalra, Seema, Karpe, Fredrik, Khadake, Jyoti, Lachance, Genevieve, Neville, Matthew, Santaniello, Adam, Caillier, Stacy J., Calabresi, Peter A., Cree, Bruce A.C., Cross, Anne, Davis, Mary F., Haines, Jonathan L., de Bakker, Paul I.W., Delgado, Silvia, Dembele, Marieme, Edwards, Keith, Fitzgerald, Kathryn C., Hakonarson, Hakon, Konidari, Ioanna, Lathi, Ellen, Manrique, Clara P., Pericak-Vance, Margaret A., Piccio, Laura, Schaefer, Cathy, McCabe, Cristin, Weiner, Howard, Goldstein, Jacqueline, Olsson, Tomas, Hadjigeorgiou, Georgios, Taylor, Bruce, Tajouri, Lotti, Charlesworth, Jac, Booth, David R., Harbo, Hanne F., Ivinson, Adrian J., Hauser, Stephen L., Compston, Alastair, Stewart, Graeme, Zipp, Frauke, Barcellos, Lisa F., Baranzini, Sergio E., Martinelli-Boneschi, Filippo, D’Alfonso, Sandra, Ziegler, Andreas, Oturai, Annette, McCauley, Jacob L., Sawcer, Stephen J., Oksenberg, Jorge R., De Jager, Philip L., Kockum, Ingrid, Hafler, David A., and Cotsapas, Chris

Published
2020
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23. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Author

Mitrovič, Mitja, Patsopoulos, Nikolaos A., Beecham, Ashley H., Dankowski, Theresa, Goris, An, Dubois, Bénédicte, D’hooghe, Marie B., Lemmens, Robin, Van Damme, Philip, Søndergaard, Helle Bach, Sellebjerg, Finn, Sorensen, Per Soelberg, Ullum, Henrik, Thørner, Lise W., Werge, Thomas, Saarela, Janna, Cournu-Rebeix, Isabelle, Damotte, Vincent, Fontaine, Bertrand, Guillot-Noel, Lena, Lathrop, Mark, Vukusik, Sandra, Gourraud, Pierre-Antoine, Andlauer, Till F.M., Pongratz, Viola, Buck, Dorothea, Gasperi, Christiane, Bayas, Antonios, Heesen, Christoph, Kümpfel, Tania, Linker, Ralf, Paul, Friedemann, Stangel, Martin, Tackenberg, Björn, Bergh, Florian Then, Warnke, Clemens, Wiendl, Heinz, Wildemann, Brigitte, Zettl, Uwe, Ziemann, Ulf, Tumani, Hayrettin, Gold, Ralf, Grummel, Verena, Hemmer, Bernhard, Knier, Benjamin, Lill, Christina M., Luessi, Felix, Dardiotis, Efthimios, Agliardi, Cristina, Barizzone, Nadia, Mascia, Elisabetta, Bernardinelli, Luisa, Comi, Giancarlo, Cusi, Daniele, Esposito, Federica, Ferrè, Laura, Comi, Cristoforo, Galimberti, Daniela, Leone, Maurizio A., Sorosina, Melissa, Mescheriakova, Julia, Hintzen, Rogier, van Duijn, Cornelia, Teunissen, Charlotte E., Bos, Steffan D., Myhr, Kjell-Morten, Celius, Elisabeth G., Lie, Benedicte A., Spurkland, Anne, Comabella, Manuel, Montalban, Xavier, Alfredsson, Lars, Stridh, Pernilla, Hillert, Jan, Jagodic, Maja, Piehl, Fredrik, Jelčić, Ilijas, Martin, Roland, Sospedra, Mireia, Ban, Maria, Hawkins, Clive, Hysi, Pirro, Kalra, Seema, Karpe, Fredrik, Khadake, Jyoti, Lachance, Genevieve, Neville, Matthew, Santaniello, Adam, Caillier, Stacy J., Calabresi, Peter A., Cree, Bruce A.C., Cross, Anne, Davis, Mary F., Haines, Jonathan L., de Bakker, Paul I.W., Delgado, Silvia, Dembele, Marieme, Edwards, Keith, Fitzgerald, Kathryn C., Hakonarson, Hakon, Konidari, Ioanna, Lathi, Ellen, Manrique, Clara P., Pericak-Vance, Margaret A., Piccio, Laura, Schaefer, Cathy, McCabe, Cristin, Weiner, Howard, Goldstein, Jacqueline, Olsson, Tomas, Hadjigeorgiou, Georgios, Taylor, Bruce, Tajouri, Lotti, Charlesworth, Jac, Booth, David R., Harbo, Hanne F., Ivinson, Adrian J., Hauser, Stephen L., Compston, Alastair, Stewart, Graeme, Zipp, Frauke, Barcellos, Lisa F., Baranzini, Sergio E., Martinelli-Boneschi, Filippo, D’Alfonso, Sandra, Ziegler, Andreas, Oturai, Annette, McCauley, Jacob L., Sawcer, Stephen J., Oksenberg, Jorge R., De Jager, Philip L., Kockum, Ingrid, Hafler, David A., and Cotsapas, Chris

Published
2019
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24. Design of TRUST, a non-interventional, multicenter, 3-year prospective study investigating an integrated patient management approach in patients with relapsing-remitting multiple sclerosis treated with natalizumab

Author

Ziemssen, Tjalf, Gass, Achim, Wuerfel, Jens, Bayas, Antonios, Tackenberg, Bjoern, Limmroth, Volker, Linker, Ralf, Maeurer, Mathias, Haas, Judith, Stangel, Martin, Meergans, Matthias, Harlin, Olof, Hartung, Hans-Peter, Ziemssen, Tjalf, Gass, Achim, Wuerfel, Jens, Bayas, Antonios, Tackenberg, Bjoern, Limmroth, Volker, Linker, Ralf, Maeurer, Mathias, Haas, Judith, Stangel, Martin, Meergans, Matthias, Harlin, Olof, and Hartung, Hans-Peter

Abstract

Background: Natalizumab provides rapid and high-efficacy control of multiple sclerosis disease activity with long-term stabilization. However, the benefits of the drug are countered by a risk of developing progressive multifocal leukoencephalopathy in patients infected with the John Cunningham Virus. Close monitoring is required in patients with increased progressive multifocal leukoencephalopathy risk receiving natalizumab in the long-term for an optimal benefit-risk evaluation. Standardized high-quality monitoring procedures may provide a superior basis for individual benefit and risk evaluation and thus improve treatment decisions. The non-interventional study TRUST was designed to capture natalizumab effectiveness under real-life conditions and to examine alternate approaches for clinical assessments, magnetic resonance imaging monitoring and use of biomarkers for progressive multifocal leukoencephalopathy risk stratification. Methods/Design: TRUST is a non-interventional, multicenter, prospective cohort study conducted at approximately 200 German neurological centers. The study is intended to enroll 1260 relapsing-remitting multiple sclerosis patients with ongoing natalizumab therapy for at least 12 months. Patients will be followed for a period of 3 years, irrespective of treatment changes after study start. Data on clinical, subclinical and patient-centric outcomes will be documented in order to compare the effectiveness of continuous versus discontinued natalizumab treatment. Furthermore, the type and frequency of clinical, magnetic resonance imaging and biomarker assessments, reasons for continuation or discontinuation of therapy and the safety profile of natalizumab will be collected to explore the impact of a systematic patient management approach and its potential impact on patient outcome. Specifically, the role of biomarkers, the use of expert opinions, the impact of high-frequency magnetic resonance imaging assessment for early progressive multifocal

Published
2016

26. Compounds in exhaled air for the detection of Alzheimer's disease

Author

Bach, Jan-Philipp, Gold, Maike, Hattesohl, Akira, Lübbe, Dirk, Mengel, David, Schmid, Severin, Tackenberg, Björn, Rieke, Jürgen, Madulla, Sasidhar, Baumbach, Jörg Ingo, Michelis, Joan, Alferink, Judith, Oertel, Wolfgang, Jessen, Frank, Vogelmeier, Claus, Dodel, Richard, and Koczulla, Rembert

Published
2013
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27. A genome-wide association study in autoimmune neurological syndromes with anti-GAD65 autoantibodies

Author

Strippel, Christine, Herrera-Rivero, Marisol, Wendorff, Mareike, Tietz, Anja K., Degenhardt, Frauke, Witten, Anika, Schroeter, Christina, Nelke, Christopher, Golombeck, Kristin S., Madlener, Marie, Rueber, Theodor, Ernst, Leon, Racz, Attila, Baumgartner, Tobias, Widman, Guido, Doppler, Kathrin, Thaler, Franziska, Siebenbrodt, Kai, Dik, Andre, Kerin, Constanze, Rauber, Saskia, Gallus, Marco, Kovac, Stjepana, Grauer, Oliver M., Grimm, Alexander, Pruess, Harald, Wickel, Jonathan, Geis, Christian, Lewerenz, Jan, Goebels, Norbert, Ringelstein, Marius, Menge, Til, Tackenberg, Bjoern, Kellinghaus, Christoph, Bien, Christian G., Kraft, Andrea, Zettl, Uwe, Ismail, Fatme Seval, Ayzenberg, Ilya, Urbanek, Christian, Suhs, Kurt-Wolfram, Tauber, Simone C., Mues, Sigrid, Kortvelyessy, Peter, Markewitz, Robert, Paliantonis, Asterios, Elger, Christian E., Surges, Rainer, Sommer, Claudia, Kumpfel, Tania, Gross, Catharina C., Lerche, Holger, Wellmer, Jorg, Quesada, Carlos M., Bergh, Florian Then, Wandinger, Klaus-Peter, Becker, Albert J., Kunz, Wolfram S., zu Hoerste, Gerd Meyer, Malter, Michael P., Rosenow, Felix, Wiendl, Heinz, Kuhlenbaumer, Gregor, Leypoldt, Frank, Lieb, Wolfgang, Franke, Andre, Meuth, Sven G., Stoll, Monika, Melzer, Nico, Strippel, Christine, Herrera-Rivero, Marisol, Wendorff, Mareike, Tietz, Anja K., Degenhardt, Frauke, Witten, Anika, Schroeter, Christina, Nelke, Christopher, Golombeck, Kristin S., Madlener, Marie, Rueber, Theodor, Ernst, Leon, Racz, Attila, Baumgartner, Tobias, Widman, Guido, Doppler, Kathrin, Thaler, Franziska, Siebenbrodt, Kai, Dik, Andre, Kerin, Constanze, Rauber, Saskia, Gallus, Marco, Kovac, Stjepana, Grauer, Oliver M., Grimm, Alexander, Pruess, Harald, Wickel, Jonathan, Geis, Christian, Lewerenz, Jan, Goebels, Norbert, Ringelstein, Marius, Menge, Til, Tackenberg, Bjoern, Kellinghaus, Christoph, Bien, Christian G., Kraft, Andrea, Zettl, Uwe, Ismail, Fatme Seval, Ayzenberg, Ilya, Urbanek, Christian, Suhs, Kurt-Wolfram, Tauber, Simone C., Mues, Sigrid, Kortvelyessy, Peter, Markewitz, Robert, Paliantonis, Asterios, Elger, Christian E., Surges, Rainer, Sommer, Claudia, Kumpfel, Tania, Gross, Catharina C., Lerche, Holger, Wellmer, Jorg, Quesada, Carlos M., Bergh, Florian Then, Wandinger, Klaus-Peter, Becker, Albert J., Kunz, Wolfram S., zu Hoerste, Gerd Meyer, Malter, Michael P., Rosenow, Felix, Wiendl, Heinz, Kuhlenbaumer, Gregor, Leypoldt, Frank, Lieb, Wolfgang, Franke, Andre, Meuth, Sven G., Stoll, Monika, and Melzer, Nico

Abstract

Autoimmune neurological syndromes (AINS) with autoantibodies against the 65kDa isoform of the glutamic acid decarboxylase (GAD65) present with limbic encephalitis, including temporal lobe seizures or epilepsy, cerebellitis with ataxia, and stiff-person-syndrome or overlap forms. Anti-GAD65 autoantibodies are also detected in autoimmune diabetes mellitus, which has a strong genetic susceptibility conferred by human leukocyte antigen (HLA) and non-HLA genomic regions. We investigated the genetic predisposition in patients with anti-GAD65 AINS. We performed a genome-wide association study (GWAS) and an association analysis of the HLA region in a large German cohort of 1214 individuals. These included 167 patients with anti-GAD65 AINS, recruited by the German Network for Research on Autoimmune Encephalitis (GENERATE), and 1047 individuals without neurological or endocrine disease as population-based controls. Predictions of protein expression changes based on GWAS findings were further explored and validated in the CSF proteome of a virtually independent cohort of 10 patients with GAD65-AINS and 10 controls. Our GWAS identified 16 genome-wide significant (P < 5 x 10(-8)) loci for the susceptibility to anti-GAD65 AINS. The top variant, rs2535288 [P = 4.42 x 10(-16), odds ratio (OR) = 0.26, 95% confidence interval (CI) = 0.187-0.358], localized to an intergenic segment in the middle of the HLA class I region. The great majority of variants in these loci (>90%) mapped to non-coding regions of the genome. Over 40% of the variants have known regulatory functions on the expression of 48 genes in disease relevant cells and tissues, mainly CD4(+) T cells and the cerebral cortex. The annotation of epigenomic marks suggested specificity for neural and immune cells. A network analysis of the implicated protein-coding genes highlighted the role of protein kinase C beta (PRKCB) and identified an enrichment of numerous biological pathways participating in immunity and neural function

30. Ofatumumab versus Teriflunomide in Multiple Sclerosis

Author

Hauser S. L., Bar-Or A., Cohen J. A., Comi G., Correale J., Coyle P. K., Cross A. H., de Seze J., Leppert D., Montalban X., Selmaj K., Wiendl H., Kerloeguen C., Willi R., Li B., Kakarieka A., Tomic D., Goodyear A., Pingili R., Haring D. A., Ramanathan K., Merschhemke M., Kappos L., Stephen L Hauser, Ludwig Kappos, Amit Bar-Or, Jeffrey A Cohen, Giancarlo Comi, Jorge Correale, Patricia K Coyle, Anne Cross, Jerome de Seze, Xavier Montalban, Krzysztof Selmaj, Heinz Wiendl, Stephen C Reingold, Garry R Cutter, Thomas Doerner, Hans-Peter Hartung, Per Soelberg Sørensen, Israel Steiner, Jerry S Wolinsky, Carlos Ballario, Christian Calvo Vildoso, Jorge Gustavo Jose, Norma Haydee Deri, Susana Liwacki, Jeannette Lechner-Scott, John Parratt, Suzanne Hodgkinson, Eva-Maria Maida, Fritz Leutmezer, Barbara Willekens, Bart Van Wijmeersch, Guy Laureys, Jo Caekebeke, Karine Geens, Ludo Vanopdenbosch, Olivier Deryck, Valerie Delvaux, Vincent Van Pesch, Ivan Milanov, Ivaylo Tarnev, Lyubomir Haralanov, Maria Manova Slavova, Penko Shotekov, Francois Emond, Francois Grandmaison, Francois Jacques, Liesly Lee, Marie Sarah Gagne Brosseau, Mark Freedman, Martin Cloutier, Robert Carruthers, Sarah Morrow, Yves Lapierre, Anton Vladic, Hana Bokun, Igor Antoncic, Marija Bosnjak Pasic, Mario Habek, Silva Butkovic Soldo, Vladimira Vuletic, Alena Martinkova, Eva Meluzinova, Ivana Stetkarova, Jan Mares, Jolana Markova, Marta Vachova, Martin Valis, Michaela Tyblova, Michal Dufek, Ondrej Skoda, Pavel Hradilek, Ana Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina Svendsen, Mads Ravnborg, Peter Vestergaard Rasmussen, Katrin Gross-Paju, Sulev Haldre, Juha Pekka Eralinna, Marja-Liisa Sumelahti, Bruno Brochet, Celine Louapre, Christine Lebrun-Frenay, David Axel Laplaud, Gilles Edan, Giovanni Castelnovo, Marc Debouverie, Patrick Vermersch, Pierre Clavelou, Pierre Labauge, Achim Berthele, Aiden Haghikia, Anselm Kornhuber, Arnfin Bergmann, Benedikt Frank, Birte Elias-Hamp, Bjoern Tackenberg, Brigitte Wildemann, Erik Strauss, Eugen Schlegel, Florian Then Bergh, Gereon Nelles, Hayrettin Tumani, Karl-Otto Sigel, Martin Stangel, Matthias Boehringer, Olaf Martin Hoffmann, Patrick Oschmann, Reinhard Hohlfeld, Silke Walter, Sylvia Menck, Till Sprenger, Tjalf Ziemssen, Veit Ulrich Becker, Vera Straeten, Konstantinos Kilidireas, Konstantinos Voumvourakis, Nikolaos Fakas, Nikolaos Grigoriadis, Agnes Koves, Csilla Rozsa, Krisztina Kovacs, Laszlo Vecsei, Satori Maria, Zita Biro, Anshu Rohatgi, Dheeraj Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha Pandit, Meena Angamuthu Kanikannan, Pahari Ghosh, Rahul Chakor, Rahul Kulkarni, Roopkumar Gursahani, Sangeeta Ravat, Srinivasa Rangasetty, Suresh Kumar, Alla Shifrin, Arnon Karni, Radi Shahien, Ron Milo, Antonio Uccelli, Carlo Pozzilli, Francesco Sacca, Giacomo Lus, Girolama Alessandra Marfia, Laura Brambilla, Marco Salvetti, Massimo Filippi, Mauro Zaffaroni, Paolo Gallo, Silvia Rossi, Simona Bonavita, Valeria Studer, Andrejs Millers, Guntis Karelis, Jolanta Kalnina, Dalia Mickeviciene, Rasa Kizlaitiene, Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Beatrijs Wokke, Bob W Van Oosten, Peter Van Domburg, Raymond Hupperts, Rogier Q Hintzen, Astrid Edland, Cesar Castaneda, Julio Perez, Martin Gavidia, Andrzej Wiak, Bartosz Karaszewski, Elzbieta Jasinska, Halina Bartosik Psujek, Iwona Jastrzebska, Jaroslaw Slawek, Maciej Maciejowski, Miroslaw Dziki, Monika Adamczyk Sowa, Robert Bonek, Waldemar Fryze, Ana Martins Da Silva, Angela Timoteo, Antonio Vasco Salgado, Carlos Capela, Carlos Veira, Filipe Correia, Joao Cerqueira, Joao De Sa, Livia De Sousa, Raquel Gouveia, Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, Dmitry Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Egon Kurca, Georgi Krastev, Miroslav Brozman, Peter Koleda, Peter Turcani, Peter Valkovic, Viera Hancinova, Vladimir Donath, Chris Retief, Michael Isaacs, Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virgina Meca Lallana, Xaviere Montalban Gairin, Fredrik Piehl, Jan Lycke, Chiara Zecca, Tobias Derfuss, Thy-Sheng Lin, Somsak Tiamkao, Ayse Nur Yuceyar, Aysun Soysal, Belgin Petek Balci, Cavit Boz, Husnu Efendi, Murat Terzi, Serhan Sevim, Serkan Ozakbas, Andrew Gale, Ben Turner, David Barnes, David Paling, Eli Silber, James Overell, Matthew Craner, Aaron Carlson, Adam Wolff, Adaeze Onuoha, Adnan Subei, Ahmad Ata, Aimee Borazanci, Akram Dastagir, Alberto Vasquez, Alison Brooke Allen, Andrew P Keegan, Angel Carrasco, Angel R Chinea Martinez, Ann Bass, Annette Okai, April Erwin, Ariel Antezana-Antezana, Barbara Green, Bharathy E Sundaram, Bhupendra Khatri, Bhupesh Dihenia, Bogdan Gheorghiu, Brian Costell, Brian Steingo, Bruce L Hughes, Carrie M Hersh, Christopher Laganke, Christopher Luzzio, Corey Ford, Craig Edward Herrman, Craig Senzon, Cynthia Huffman, Daniel R Wynn, David D O Bear, David Lesch, David H Mattson, David Weisman, Deborah A Burke, Dennis W Dietrich, Deren Huang, Derrick Robertson, Djamchid Lotfi, Don Joseph Alfonso, Dusan Stefoski, Edward J Fox, Emily Pharr, Enrique Alvarez, Evanthia Bernitsas, Faria Amjad, Gabriel Pardo, Geoffrey Eubank, Gerald Mcintosh, Giles F Crowell, Hemanth Rao, J Michael Hemphill, Jack H Florin, Jacqueline Nicholas, James Napier, James Scott, Jason M Silversteen, Javier Vasallo, Jean-Raphael Schneider, Jeanette Wendt, Jeffrey Cohen, Jeffrey Gross, Jeffrey Groves, Jeffrey Kaplan, Jessica Stulc, Joanna A Cooper, John Foley, John Scagnelli, Jonathan C Calkwood, Jose Pizarro Otero, Jose Rafecas, Joshua Katz, Juliette S Saad, Katherine Standley, Keith Edwards, Kenneth Sharlin, Khurram Bashir, Kimberly Wagner, Kore Liow, Larry Lee Blankenship Jr, Laszlo Mate, Liliana Montoya, Lon D Lynn, Mark Agius, Mark Cascione, Mark Allan Goldstein, Mark Janicki, Martin R Bialow, Mary Denise Hughes, Matthew J Baker, Michelle Apperson, Michelle B Kuczma, M Mateo Paz Soldan, Mirela Cerghet, Nathaniel Robb Whaley, Paul K Winner, Pavle Repovic, Praful Kelkar, Romero Rekha Pillai, Ricardo Ayala, Richard Sater, Randall Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert Naismith, Ronald S Murray, Samuel Hunter, Sara Qureshi, Sharon Lynch, Sibyl Wray, Silvia R Delgado, Stacy Donlon, Stanley Cohan, Stanya Smith, Stuart James Shafer, Susan Azalone, Susan Hibbs, Tamara A Miller, Thomas Giancarlo, Troy Desai, Varun K Saxena, Virginia Simnad, William David Honeycutt, William Logan, William E McElveen, William Wagner, University of California [San Francisco] (UCSF), University of California, Perelman School of Medicine, University of Pennsylvania [Philadelphia], Cleveland Clinic, IRCCS Ospedale San Raffaele [Milan, Italy], Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia [Buenos Aires] (FLENI), FLENI, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, University Hospital Basel [Basel], Vall d'Hebron University Hospital [Barcelona], University of Warmia and Mazury [Olsztyn], University of Münster, Novartis Pharma S.A.S., Novartis Pharmaceuticals, University of Basel (Unibas), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Willekens, Barbara, ASCLEPIOS I and ASCLEPIOS II Trial Groups, Hauser, S. L., Bar-Or, A., Cohen, J. A., Comi, G., Correale, J., Coyle, P. K., Cross, A. H., de Seze, J., Leppert, D., Montalban, X., Selmaj, K., Wiendl, H., Kerloeguen, C., Willi, R., Li, B., Kakarieka, A., Tomic, D., Goodyear, A., Pingili, R., Haring, D. A., Ramanathan, K., Merschhemke, M., Kappos, L., Asclepios, I and ASCLEPIOS II Trial Group, Filippi, M, L Hauser, Stephen, Kappos, Ludwig, Bar-Or, Amit, A Cohen, Jeffrey, Comi, Giancarlo, Correale, Jorge, K Coyle, Patricia, Cross, Anne, de Seze, Jerome, Montalban, Xavier, Selmaj, Krzysztof, Wiendl, Heinz, C Reingold, Stephen, R Cutter, Garry, Doerner, Thoma, Hartung, Hans-Peter, Soelberg Sørensen, Per, Steiner, Israel, S Wolinsky, Jerry, Ballario, Carlo, Calvo Vildoso, Christian, Gustavo Jose, Jorge, Haydee Deri, Norma, Liwacki, Susana, Lechner-Scott, Jeannette, Parratt, John, Hodgkinson, Suzanne, Maida, Eva-Maria, Leutmezer, Fritz, Van Wijmeersch, Bart, Laureys, Guy, Caekebeke, Jo, Geens, Karine, Vanopdenbosch, Ludo, Deryck, Olivier, Delvaux, Valerie, Van Pesch, Vincent, Milanov, Ivan, Tarnev, Ivaylo, Haralanov, Lyubomir, Manova Slavova, Maria, Shotekov, Penko, Emond, Francoi, Grandmaison, Francoi, Jacques, Francoi, Lee, Liesly, Sarah Gagne Brosseau, Marie, Freedman, Mark, Cloutier, Martin, Carruthers, Robert, Morrow, Sarah, Lapierre, Yve, Vladic, Anton, Bokun, Hana, Antoncic, Igor, Bosnjak Pasic, Marija, Habek, Mario, Butkovic Soldo, Silva, Vuletic, Vladimira, Martinkova, Alena, Meluzinova, Eva, Stetkarova, Ivana, Mares, Jan, Markova, Jolana, Vachova, Marta, Valis, Martin, Tyblova, Michaela, Dufek, Michal, Skoda, Ondrej, Hradilek, Pavel, Voldsgaard Jensen, Ana, Hvilsted Nielsen, Helle, Svendsen, Kristina, Ravnborg, Mad, Vestergaard Rasmussen, Peter, Gross-Paju, Katrin, Haldre, Sulev, Pekka Eralinna, Juha, Sumelahti, Marja-Liisa, Brochet, Bruno, Louapre, Celine, Lebrun-Frenay, Christine, Axel Laplaud, David, Edan, Gille, Castelnovo, Giovanni, Debouverie, Marc, Vermersch, Patrick, Clavelou, Pierre, Labauge, Pierre, Berthele, Achim, Haghikia, Aiden, Kornhuber, Anselm, Bergmann, Arnfin, Frank, Benedikt, Elias-Hamp, Birte, Tackenberg, Bjoern, Wildemann, Brigitte, Strauss, Erik, Schlegel, Eugen, Then Bergh, Florian, Nelles, Gereon, Tumani, Hayrettin, Sigel, Karl-Otto, Stangel, Martin, Boehringer, Matthia, Martin Hoffmann, Olaf, Oschmann, Patrick, Hohlfeld, Reinhard, Walter, Silke, Menck, Sylvia, Sprenger, Till, Ziemssen, Tjalf, Ulrich Becker, Veit, Straeten, Vera, Kilidireas, Konstantino, Voumvourakis, Konstantino, Fakas, Nikolao, Grigoriadis, Nikolao, Koves, Agne, Rozsa, Csilla, Kovacs, Krisztina, Vecsei, Laszlo, Maria, Satori, Biro, Zita, Rohatgi, Anshu, Khurana, Dheeraj, Durai Pandian, Jeyaraj, Dev Mukherji, Joy, Pandit, Lekha, Angamuthu Kanikannan, Meena, Ghosh, Pahari, Chakor, Rahul, Kulkarni, Rahul, Gursahani, Roopkumar, Ravat, Sangeeta, Rangasetty, Srinivasa, Kumar, Suresh, Shifrin, Alla, Karni, Arnon, Shahien, Radi, Milo, Ron, Uccelli, Antonio, Pozzilli, Carlo, Sacca, Francesco, Lus, Giacomo, Alessandra Marfia, Girolama, Brambilla, Laura, Salvetti, Marco, Filippi, Massimo, Zaffaroni, Mauro, Gallo, Paolo, Rossi, Silvia, Bonavita, Simona, Studer, Valeria, Millers, Andrej, Karelis, Gunti, Kalnina, Jolanta, Mickeviciene, Dalia, Kizlaitiene, Rasa, Carbajal Ramirez, Angelica, Jose Lopez Prieto, Juan, Wokke, Beatrij, W Van Oosten, Bob, Van Domburg, Peter, Hupperts, Raymond, Q Hintzen, Rogier, Edland, Astrid, Castaneda, Cesar, Perez, Julio, Gavidia, Martin, Wiak, Andrzej, Karaszewski, Bartosz, Jasinska, Elzbieta, Bartosik Psujek, Halina, Jastrzebska, Iwona, Slawek, Jaroslaw, Maciejowski, Maciej, Dziki, Miroslaw, Adamczyk Sowa, Monika, Bonek, Robert, Fryze, Waldemar, Martins Da Silva, Ana, Timoteo, Angela, Vasco Salgado, Antonio, Capela, Carlo, Veira, Carlo, Correia, Filipe, Cerqueira, Joao, De Sa, Joao, De Sousa, Livia, Gouveia, Raquel, Sergeevna Agafina, Alina, Naumovna Belova, Anna, Viktorovich Sazonov, Deni, Pokhabov, Dmitry, Igorevna Kairbekova, Ekaterina, Gennadievna Arefieva, Elena, Axatovich Khabirov, Farit, Vyacheslavovich Litvinenko, Igor, Stolyarov, Igor, Aleksandrovna Sokolova, Irina, Ivanovna Volkova, Larisa, Vafaevna Davydovskaya, Maria, Nikolaevna Zaharova, Maria, Alekseevna Malkova, Nadezhda, Agafonovna Totolyan, Natalia, Vasilievich Dorogov, Nikolay, Anatolievna Sivertseva, Stella, Kurca, Egon, Krastev, Georgi, Brozman, Miroslav, Koleda, Peter, Turcani, Peter, Valkovic, Peter, Hancinova, Viera, Donath, Vladimir, Retief, Chri, Isaacs, Michael, Saiz Hinarejos, Albert, Rodriguez Antigüedad, Alfredo, Casanova Estruch, Bonaventura, Oreja-Guevara, Celia, Reig Rosello, Gemma, Carlos Alvarez Cermeño, Jose, Martinez Rodriguez, Jose, Meca Lallana, Jose, Antonio Garcia Merino, Juan, Forero Diaz, Lucia, Costa Frossard Franca, Lucienne, Querol Gutierrez, Lui, Ramio Torrenta, Llui, Serrano Castro, Pedro, Arroyo Gonzalez, Rafael, Eichau Madueño, Sara, Martinez Yelamos, Sergio, Castillo Trivino, Tamara, Meca Lallana, Virgina, Montalban Gairin, Xaviere, Piehl, Fredrik, Lycke, Jan, Zecca, Chiara, Derfuss, Tobia, Lin, Thy-Sheng, Tiamkao, Somsak, Nur Yuceyar, Ayse, Soysal, Aysun, Petek Balci, Belgin, Boz, Cavit, Efendi, Husnu, Terzi, Murat, Sevim, Serhan, Ozakbas, Serkan, Gale, Andrew, Turner, Ben, Barnes, David, Paling, David, Silber, Eli, Overell, Jame, Craner, Matthew, Carlson, Aaron, Wolff, Adam, Onuoha, Adaeze, Subei, Adnan, Ata, Ahmad, Borazanci, Aimee, Dastagir, Akram, Vasquez, Alberto, Brooke Allen, Alison, P Keegan, Andrew, Carrasco, Angel, R Chinea Martinez, Angel, Bass, Ann, Okai, Annette, Erwin, April, Antezana-Antezana, Ariel, Green, Barbara, E Sundaram, Bharathy, Khatri, Bhupendra, Dihenia, Bhupesh, Gheorghiu, Bogdan, Costell, Brian, Steingo, Brian, L Hughes, Bruce, M Hersh, Carrie, Laganke, Christopher, Luzzio, Christopher, Ford, Corey, Edward Herrman, Craig, Senzon, Craig, Huffman, Cynthia, R Wynn, Daniel, O Bear, David D, Lesch, David, H Mattson, David, Weisman, David, A Burke, Deborah, W Dietrich, Denni, Huang, Deren, Robertson, Derrick, Lotfi, Djamchid, Joseph Alfonso, Don, Stefoski, Dusan, J Fox, Edward, Pharr, Emily, Alvarez, Enrique, Bernitsas, Evanthia, Amjad, Faria, Pardo, Gabriel, Eubank, Geoffrey, Mcintosh, Gerald, F Crowell, Gile, Rao, Hemanth, Michael Hemphill, J, H Florin, Jack, Nicholas, Jacqueline, Napier, Jame, Scott, Jame, M Silversteen, Jason, Vasallo, Javier, Schneider, Jean-Raphael, Wendt, Jeanette, Cohen, Jeffrey, Gross, Jeffrey, Groves, Jeffrey, Kaplan, Jeffrey, Stulc, Jessica, A Cooper, Joanna, Foley, John, Scagnelli, John, C Calkwood, Jonathan, Pizarro Otero, Jose, Rafecas, Jose, Katz, Joshua, S Saad, Juliette, Standley, Katherine, Edwards, Keith, Sharlin, Kenneth, Bashir, Khurram, Wagner, Kimberly, Liow, Kore, Lee Blankenship Jr, Larry, Mate, Laszlo, Montoya, Liliana, D Lynn, Lon, Agius, Mark, Cascione, Mark, Allan Goldstein, Mark, Janicki, Mark, R Bialow, Martin, Denise Hughes, Mary, J Baker, Matthew, Apperson, Michelle, B Kuczma, Michelle, Mateo Paz Soldan, M, Cerghet, Mirela, Robb Whaley, Nathaniel, K Winner, Paul, Repovic, Pavle, Kelkar, Praful, Rekha Pillai, Romero, Ayala, Ricardo, Sater, Richard, Trudell, Randall, Fairborn Armstrong, Robert, Thomas Nahouraii, Robert, Naismith, Robert, S Murray, Ronald, Hunter, Samuel, Qureshi, Sara, Lynch, Sharon, Wray, Sibyl, R Delgado, Silvia, Donlon, Stacy, Cohan, Stanley, Smith, Stanya, James Shafer, Stuart, Azalone, Susan, Hibbs, Susan, A Miller, Tamara, Giancarlo, Thoma, Desai, Troy, K Saxena, Varun, Simnad, Virginia, David Honeycutt, William, Logan, William, E McElveen, William, Wagner, William, Stephen, L Hauser, Ludwig, Kappo, Amit, Bar-Or, Jeffrey, A Cohen, Giancarlo, Comi, Jorge, Correale, Patricia, K Coyle, Anne, Cro, Jerome de Seze, Xavier, Montalban, Krzysztof, Selmaj, Heinz, Wiendl, Stephen, C Reingold, Garry, R Cutter, Thomas, Doerner, Hans-Peter, Hartung, Per Soelberg Sørensen, Israel, Steiner, Jerry, S Wolinsky, Carlos, Ballario, Christian Calvo Vildoso, Jorge Gustavo Jose, Norma Haydee Deri, Susana, Liwacki, Jeannette, Lechner-Scott, John, Parratt, Suzanne, Hodgkinson, Eva-Maria, Maida, Fritz, Leutmezer, Barbara, Willeken, Bart Van Wijmeersch, Guy, Laurey, Karine, Geen, Ludo, Vanopdenbosch, Olivier, Deryck, Valerie, Delvaux, Vincent Van Pesch, Ivan, Milanov, Ivaylo, Tarnev, Lyubomir, Haralanov, Maria Manova Slavova, Penko, Shotekov, Francois, Emond, Francois, Grandmaison, Francois, Jacque, Liesly, Lee, Marie Sarah Gagne Brosseau, Mark, Freedman, Martin, Cloutier, Robert, Carruther, Sarah, Morrow, Yves, Lapierre, Anton, Vladic, Hana, Bokun, Igor, Antoncic, Marija Bosnjak Pasic, Mario, Habek, Silva Butkovic Soldo, Vladimira, Vuletic, Alena, Martinkova, Eva, Meluzinova, Ivana, Stetkarova, Jan, Mare, Jolana, Markova, Marta, Vachova, Martin, Vali, Michaela, Tyblova, Michal, Dufek, Ondrej, Skoda, Pavel, Hradilek, Ana Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina, Svendsen, Mads, Ravnborg, Peter Vestergaard Rasmussen, Katrin, Gross-Paju, Sulev, Haldre, Juha Pekka Eralinna, Marja-Liisa, Sumelahti, Bruno, Brochet, Celine, Louapre, Christine, Lebrun-Frenay, David Axel Laplaud, Gilles, Edan, Giovanni, Castelnovo, Marc, Debouverie, Patrick, Vermersch, Pierre, Clavelou, Pierre, Labauge, Achim, Berthele, Aiden, Haghikia, Anselm, Kornhuber, Arnfin, Bergmann, Benedikt, Frank, Birte, Elias-Hamp, Bjoern, Tackenberg, Brigitte, Wildemann, Erik, Strau, Eugen, Schlegel, Florian Then Bergh, Gereon, Nelle, Hayrettin, Tumani, Karl-Otto, Sigel, Martin, Stangel, Matthias, Boehringer, Olaf Martin Hoffmann, Patrick, Oschmann, Reinhard, Hohlfeld, Silke, Walter, Sylvia, Menck, Till, Sprenger, Tjalf, Ziemssen, Veit Ulrich Becker, Vera, Straeten, Konstantinos, Kilidirea, Konstantinos, Voumvouraki, Nikolaos, Faka, Nikolaos, Grigoriadi, Agnes, Kove, Csilla, Rozsa, Krisztina, Kovac, Laszlo, Vecsei, Satori, Maria, Zita, Biro, Anshu, Rohatgi, Dheeraj, Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha, Pandit, Meena Angamuthu Kanikannan, Pahari, Ghosh, Rahul, Chakor, Rahul, Kulkarni, Roopkumar, Gursahani, Sangeeta, Ravat, Srinivasa, Rangasetty, Suresh, Kumar, Alla, Shifrin, Arnon, Karni, Radi, Shahien, Ron, Milo, Antonio, Uccelli, Carlo, Pozzilli, Sacca', Francesco, Giacomo, Lu, Girolama Alessandra Marfia, Laura, Brambilla, Marco, Salvetti, Massimo, Filippi, Mauro, Zaffaroni, Paolo, Gallo, Silvia, Rossi, Simona, Bonavita, Valeria, Studer, Andrejs, Miller, Guntis, Kareli, Jolanta, Kalnina, Dalia, Mickeviciene, Rasa, Kizlaitiene, Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Beatrijs, Wokke, Bob, W Van Oosten, Peter Van Domburg, Raymond, Huppert, Rogier, Q Hintzen, Astrid, Edland, Cesar, Castaneda, Julio, Perez, Martin, Gavidia, Andrzej, Wiak, Bartosz, Karaszewski, Elzbieta, Jasinska, Halina Bartosik Psujek, Iwona, Jastrzebska, Jaroslaw, Slawek, Maciej, Maciejowski, Miroslaw, Dziki, Monika Adamczyk Sowa, Robert, Bonek, Waldemar, Fryze, Ana Martins Da Silva, Angela, Timoteo, Antonio Vasco Salgado, Carlos, Capela, Carlos, Veira, Filipe, Correia, Joao, Cerqueira, Joao De Sa, Livia De Sousa, Raquel, Gouveia, Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, Dmitry, Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor, Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Egon, Kurca, Georgi, Krastev, Miroslav, Brozman, Peter, Koleda, Peter, Turcani, Peter, Valkovic, Viera, Hancinova, Vladimir, Donath, Chris, Retief, Michael, Isaac, Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia, Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virgina Meca Lallana, Xaviere Montalban Gairin, Fredrik, Piehl, Jan, Lycke, Chiara, Zecca, Tobias, Derfu, Thy-Sheng, Lin, Somsak, Tiamkao, Ayse Nur Yuceyar, Aysun, Soysal, Belgin Petek Balci, Cavit, Boz, Husnu, Efendi, Murat, Terzi, Serhan, Sevim, Serkan, Ozakba, Andrew, Gale, Ben, Turner, David, Barne, David, Paling, Eli, Silber, James, Overell, Matthew, Craner, Aaron, Carlson, Adam, Wolff, Adaeze, Onuoha, Adnan, Subei, Ahmad, Ata, Aimee, Borazanci, Akram, Dastagir, Alberto, Vasquez, Alison Brooke Allen, Andrew, P Keegan, Angel, Carrasco, Angel, R Chinea Martinez, Ann, Ba, Annette, Okai, April, Erwin, Ariel, Antezana-Antezana, Barbara, Green, Bharathy, E Sundaram, Bhupendra, Khatri, Bhupesh, Dihenia, Bogdan, Gheorghiu, Brian, Costell, Brian, Steingo, Bruce, L Hughe, Carrie, M Hersh, Christopher, Laganke, Christopher, Luzzio, Corey, Ford, Craig Edward Herrman, Craig, Senzon, Cynthia, Huffman, Daniel, R Wynn, David D, O Bear, David, Lesch, David, H Mattson, David, Weisman, Deborah, A Burke, Dennis, W Dietrich, Deren, Huang, Derrick, Robertson, Djamchid, Lotfi, Don Joseph Alfonso, Dusan, Stefoski, Edward, J Fox, Emily, Pharr, Enrique, Alvarez, Evanthia, Bernitsa, Faria, Amjad, Gabriel, Pardo, Geoffrey, Eubank, Gerald, Mcintosh, Giles, F Crowell, Hemanth, Rao, J Michael Hemphill, Jack, H Florin, Jacqueline, Nichola, James, Napier, James, Scott, Jason, M Silversteen, Javier, Vasallo, Jean-Raphael, Schneider, Jeanette, Wendt, Jeffrey, Cohen, Jeffrey, Gro, Jeffrey, Grove, Jeffrey, Kaplan, Jessica, Stulc, Joanna, A Cooper, John, Foley, John, Scagnelli, Jonathan, C Calkwood, Jose Pizarro Otero, Jose, Rafeca, Joshua, Katz, Juliette, S Saad, Katherine, Standley, Keith, Edward, Kenneth, Sharlin, Khurram, Bashir, Kimberly, Wagner, Kore, Liow, Larry Lee Blankenship Jr, Laszlo, Mate, Liliana, Montoya, Lon, D Lynn, Mark, Agiu, Mark, Cascione, Mark Allan Goldstein, Mark, Janicki, Martin, R Bialow, Mary Denise Hughes, Matthew, J Baker, Michelle, Apperson, Michelle, B Kuczma, M Mateo Paz Soldan, Mirela, Cerghet, Nathaniel Robb Whaley, Paul, K Winner, Pavle, Repovic, Praful, Kelkar, Romero Rekha Pillai, Ricardo, Ayala, Richard, Sater, Randall, Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert, Naismith, Ronald, S Murray, Samuel, Hunter, Sara, Qureshi, Sharon, Lynch, Sibyl, Wray, Silvia, R Delgado, Stacy, Donlon, Stanley, Cohan, Stanya, Smith, Stuart James Shafer, Susan, Azalone, Susan, Hibb, Tamara, A Miller, Thomas, Giancarlo, Troy, Desai, Varun, K Saxena, Virginia, Simnad, William David Honeycutt, William, Logan, William, E McElveen, William, Wagner, University of California [San Francisco] (UC San Francisco), University of California (UC), University of Pennsylvania, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Herrada, Anthony, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Male, MESH: Multiple Sclerosis, Relapsing-Remitting, T-Lymphocytes, Hydroxybutyrates, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Pharmacology, Relapsing-Remitting, MESH: Magnetic Resonance Imaging, chemistry.chemical_compound, 0302 clinical medicine, Teriflunomide, Monoclonal, MESH: Double-Blind Method, 030212 general & internal medicine, Humanized, MESH: Toluidines, B-Lymphocytes, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Subcutaneous, B-Lymphocyte, Brain, General Medicine, Magnetic Resonance Imaging, MESH: Crotonates, Crotonates, Pyrimidine metabolism, Disease Progression, Female, MESH: Disease Progression, Antibody, Human, Adult, Multiple Sclerosis, Toluidines, medicine.drug_class, Injections, Subcutaneous, Injections, Subcutaneou, Monoclonal antibody, Ofatumumab, Settore MED/26, Antibodies, Monoclonal, Humanized, Crotonate, Antibodies, Injections, 03 medical and health sciences, MESH: Brain, Multiple Sclerosis, Relapsing-Remitting, Double-Blind Method, MESH: B-Lymphocytes, Nitriles, medicine, Humans, MESH: Kaplan-Meier Estimate, MESH: Humans, business.industry, Multiple sclerosis, MESH: Injections, Subcutaneous, MESH: Adult, medicine.disease, MESH: Male, MESH: T-Lymphocytes, T-Lymphocyte, Multicenter study, chemistry, MESH: Antibodies, Monoclonal, Humanized, biology.protein, Human medicine, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P

Published
2020
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31. Autorinnen und Autoren

Author

Ackermann, Hermann, Angstwurm, Heinz, Aschoff, Alfred, Banaschewski, Tobias, Baron, Ralf, Bartels, Claudius, Bartsch, Thorsten, Bayas, Antonios, Bender, Andreas, Benecke, Reiner, Berger, Mathias, Beuche, Wolfgang, Brand, Thomas, Ciarenbach, Peter, von Cramon, D. Yves, Curt, Armin, Deuschl, Günther, Diete, Sabine, Dieterich, Marianne, Dietz, Volker, Dietzmann, Knut, Ebersbach, Georg, Eiffert, Helmut, Engelhardt, Andreas, Erbguth, Frank, Ferbert, Andreas, Firsching, Raimund, Förderreuther, Stefanie, Förstl, Hans, Gaidzik, Peter W., Gärtner, Jutta, Gasser, Thomas, Goebel, Hans H., Görtier, Michael, Gold, Ralf, Goldenberg, Georg, Grehl, Holger, Grzyska, Ulrich, Hamann, Gerhard F., Klinik, Horst Schmidt, Hansen, Hans-Christian, Harms, Lutz, Haupt, Walter F., Hausotter, Wolfgang, Heide, Wolfgang, Heinen, Florian, von Haunersches, Kinderspital, Henningsen, Henning, Herholz, Karl, Hilz, Max J., Hug, Andreas, Hummelsheim, Horst, Janzen, Rudolf W.C., Jaspert-Grehl, Andrea, Johannsen-Horbach, Helga, Jüngling, Freimut D., Jurkat-Rott, Karin, Kapfhammer, Hans-Peter, Karnath, Hans-Otto, Klein, Karl M., Klockgether, Thomas, Kölmel, Hans W., Kolominsky-Rabas, Peter, Kömpf, Detlef, Kopp, Bruno, Krägeloh-Mann, Ingeborg, Krämer, Günter, Lang, Christoph J.G., Lehmann-Horn, Frank, Lins, Hartmut, Maurer, Mathias, Mauch, Erich, Masuhr, Florian, Marx, Peter, Meier, Uwe, Mirisch, Stephan, Möller, Jens C., Moschner, Carsten, Müller-Vahl, Hermann, Nau, Roland, Neveling, Michael, Oertel, Wolfgang H., Pellkofer, Hannah, Poser, Sigrid, Reichmann, Heinz, Reiners, Karlheinz, Reinhardt, Frank M., Rieckmann, Peter, Rosier, Norbert, Röβner, Veit, Rolfs, Arndt, Rosenow, Felix, Rothenberger, Aribert, Schäfer, Jochen, Schipper, Hayo I., Schlegel, Uwe, Schlote, Andrea, Schmidt, Roger, Schmidtke, Klaus, Schnider, Armin, Schönle, Paul W., Schreiber, Herbert, Schubotz, Ricarda I., Schumacher, Martin, Schurch, Brigitte, Schuster, Gabriele, Schwab, Stefan, Sommer, Claudia, Specht, Ulrich, Sprenger, Till, Stefan, Hermann, Steinhoff, Bernhard J., Stoll, Guido, Strauss, Walter C., Sturm, Walter, Tackenberg, Björn, Tauer, Ulrike, Tettenborn, Barbara, Thoden, Uwe, Thorbecke, Rupprecht, Tolle, Thomas R., Toyka, Klaus V., Traufeller, Kathrin, Vogel, Hans-Peter, Voltz, Raymond, Wallesch, Claus-Werner, Wessel, Karl, Wiedemann, Falk, Witt, Andreas, Wunderlich, Michael T., Zerr, Inga, Zeumer, Herman, Zierz, Stephan, Zihl, Josef, Ziemssen, Tjalf, and Zysset, Stefan

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