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1. Coupling Optical and Electrical Measurements in Artificial Membranes: Lateral Diffusion of Lipids and Channel Forming Peptides in Planar Bilayers

Author

Duclohier H, Helluin O, Lea E, Mackie AR, and Ladha S

Subjects
electric conductivity, lipid bilayers, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Planar lipid bilayers (PLB) were prepared by the Montal-Mueller technique in a FRAP system designed to simultaneously measure conductivity across, and lateral diffusion of, the bilayer. In the first stage of the project the FRAP system was used to characterise the lateral dynamics of bilayer lipids with regards to phospholipid composition (headgroup, chain unsaturation etc.), presence of cholesterol and the effect of divalent cations on negatively-charged bilayers. In the second stage of the project, lateral diffusion of two fluorescently-labelled voltage-dependent pore-forming peptides (alamethicin and S4s from Shaker K+ channel) was determined at rest and in the conducting state. This study demonstrates the feasibility of such experiments with PLBs, amenable to physical constraints, and thus offers new opportunities for systematic studies of structure-function relationships in membrane-associating molecules.

Published
1998
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3. Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Sabet, A., George, K., Roberts, L., Carne, R., Blum, S., Henderson, R., Van Damme, P., Demeestere, J., Larue, S., D'Amour, C., Bril, V., Breiner, A., 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., Zschuentssch, 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., Alberti Aguiló, M., Gamez, J., Figueras, M., Marquez Infante, C., Benitez Rivero, S., Lunn, M., Morrow, J., Gosal, D., Lavin, T., Melamed, I., Testori, A., Ajroud-Driss, S., Menichella, D., Simpson, E., Chi-Ho Lai, E., 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., van Schaik, Ivo N, Bril, Vera, van Geloven, Nan, Hartung, Hans-Peter, Lewis, Richard A, Sobue, Gen, Lawo, John-Philip, Praus, Michaela, Mielke, Orell, Durn, Billie L, Cornblath, David R, and Merkies, Ingemar S J

Published
2018
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4. Comparing Four Medicines to Treat Pain from Cryptogenic Sensory Polyneuropathy—The PAIN-CONTRoLS Study

Author

Barohn, Richard, primary, Gajewski, B, additional, Pasnoor, M, additional, Brown, L, additional, Herbelin1, L, additional, Kimminau, K, additional, Jawdat, O, additional, Liu, T, additional, Parks, C, additional, Shlemon, P, additional, Dimachkie, M, additional, Pascuzzi, R, additional, Ahmed, A, additional, Wicklund, M, additional, Smith, G, additional, Heitzman, D, additional, Ladha, S, additional, Pulley, M, additional, Li, Y, additional, Lewis, R, additional, Sharma, K, additional, Tobon, A, additional, Walk, D, additional, Brannagan, T, additional, Quan, D, additional, Trivedi, J, additional, Iyadurai, S, additional, Kissel, J, additional, Stino, A, additional, Wolfe, G, additional, Hayat, G, additional, Thaisetthawatkul, P, additional, Biliciler, S, additional, Salajegheh, K, additional, Hehir, M, additional, Kolb, N, additional, Burns, T, additional, Bril, V, additional, Austin, S, additional, Jacoby, M, additional, Vu, T, additional, Bazant, M, additional, Karam, C, additional, Hussainn, Y, additional, Kutz, C, additional, Twydell, P, additional, Scelsa, S, additional, Kushlaf, H, additional, Wymer, J, additional, Mallonee, W, additional, Ralph, J, additional, Barboi, A, additional, Verma, N, additional, Ahmed, M, additional, Memon, A, additional, Ramchandren, S, additional, Saperstein, D, additional, Lou, J, additional, Swenson, A, additional, and Cash, T, additional

Published
2020
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5. Theme 09 - Clinical Trials and Trial Design.

Author

Badri, S., Mason, J., Paganoni, S., Timmons, J., Yeramian, P., Cudkowicz, M., Appel, S., Ladha, S., Maragakis, N., Rivner, M., Katz, J., Genge, A., Olney, N., Lange, D., Heitzman, D., Bodkin, C., Jawdat, O., Goyal, N., Bornstein, J., and Mak, C.

Subjects
EXPERIMENTAL design, AMYOTROPHIC lateral sclerosis, PROTECTION motivation theory
Abstract

ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair. A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of Reldesemtiv In Patients With ALS. CAPTURE ALS: the comprehensive analysis platform to understand, remedy and eliminate ALS. [Extracted from the article]

Published
2022
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6. Current treatment practice of Guillain-Barré syndrome

Author

Verboon, C, Doets, A, Galassi, G, Davidson, A, Waheed, W, Pereon, Y, Shahrizaila, N, Kusunoki, S, Lehmann, H, Harbo, T, Monges, S, Van Den Bergh, P, Willison, H, Cornblath, D, Jacobs, B, Hughes, R, Gorson, K, Hartung, H, Van Doorn, P, Van den Berg, B, Roodbol, J, Van Woerkom, M, Reisin, R, Reddel, S, Islam, Z, Islam, B, Mohammad, Q, Feasby, T, Dardiotis, E, Nobile-Orazio, E, Bateman, K, Illa, I, Querol, L, Hsieh, S, Chavada, G, Addington, J, Ajroud-Driss, S, Andersen, H, Antonini, G, Ariatti, A, Attarian, S, Badrising, U, Barroso, F, Benedetti, L, Beronio, A, Bianco, M, Binda, D, Briani, C, Bunschoten, C, Burmann, J, Bella, I, Bertorini, T, Bhavaraju-Sanka, R, Brannagan, T, Busby, M, Butterworth, S, Casasnovas, C, Cavaletti, G, Chao, C, Chen, S, Chetty, S, Claeys, K, Conti, M, Cosgrove, J, Dalakas, M, Demichelis, C, Derejko, M, Dillmann, U, Dimachkie, M, Doppler, K, Dornonville de la Cour, C, Echaniz-Laguna, A, Eftimov, F, Faber, C, Fazio, R, Fokke, C, Fujioka, T, Fulgenzi, E, Garcia-Sobrino, T, Garssen, M, Georgios, H, Gijsbers, C, Gilchrist, J, Gilhuis, J, Giorli, E, Goldstein, J, Goyal, N, Granit, V, Grapperon, A, Gutierrez, G, Hadden, R, Holbech, J, Holt, J, Pedret, C, Htut, M, Jellema, K, Pascual, I, Jimeno-Montero, M, Kaida, K, Karafiath, S, Katzberg, H, Kiers, L, Kieseier, B, Kimpinski, K, Kleyweg, R, Kokubun, N, Kolb, N, Kuitwaard, K, Kuwabara, S, Kwan, J, Ladha, S, Lassen, L, Lawson, V, Ledingham, D, Lucy, S, Lunn, M, Magot, A, Manji, H, Marchesoni, C, Marfia, G, Infante, C, Hernandez, E, Mataluni, G, Mattiazi, M, Mcdermott, C, Meekins, G, Miller, J, Moris de la Tassa, G, Physiotherapist, J, Nascimbene, C, Nowak, R, Balaguer, P, Osei-Bonsu, M, Pan, E, Pardal, A, Pardo, J, Pasnoor, M, Pulley, M, Rajabally, Y, Rinaldi, S, Ritter, C, Roberts, R, Rojas-Marcos, I, Rudnicki, S, Ruiz, M, Sachs, G, Samijn, J, Santoro, L, Savransky, A, Schenone, A, Schwindling, L, Tous, M, Sekiguchi, Y, Sheikh, K, Silvestri, N, Sindrup, S, Sommer, C, Stein, B, Stino, A, Spyropoulos, A, Srinivasan, J, Styliani, R, Suzuki, H, Tankisi, H, Tigner, D, Twydell, P, Van Damme, P, Van der Kooi, A, Van Dijk, G, Van der Ree, T, Van Koningsveld, R, Valzania, F, Varrato, J, Vermeij, F, Verschuuren, J, Visser, L, Vytopil, M, Wilken, M, Wilkerson, C, Wirtz, P, Yamagishi, Y, Zhou, L, Zivkovic, S, Verboon C., Doets A. Y., Galassi G., Davidson A., Waheed W., Pereon Y., Shahrizaila N., Kusunoki S., Lehmann H. C., Harbo T., Monges S., Van Den Bergh P., Willison H. J., Cornblath D. R., Jacobs B. C., Hughes R. A. C., Gorson K. C., Hartung H. P., Van Doorn P. A., Van den Berg B., Roodbol J., Van Woerkom M., Reisin R. C., Reddel S. W., Islam Z., Islam B., Mohammad Q. D., Feasby T. E., Dardiotis E., Nobile-Orazio E., Bateman K., Illa I., Querol L., Hsieh S. T., Chavada G., Addington J. M., Ajroud-Driss S., Andersen H., Antonini G., Ariatti A., Attarian S., Badrising U. A., Barroso F. A., Benedetti L., Beronio A., Bianco M., Binda D., Briani C., Bunschoten C., Burmann J., Bella I. R., Bertorini T. E., Bhavaraju-Sanka R., Brannagan T. H., Busby M., Butterworth S., Casasnovas C., Cavaletti G., Chao C. C., Chen S., Chetty S., Claeys K. G., Conti M. E., Cosgrove J. S., Dalakas MC., Demichelis C., Derejko M. A., Dillmann U., Dimachkie M. M., Doppler K., Dornonville de la Cour C., Echaniz-Laguna A., Eftimov F., Faber C. G., Fazio R., Fokke C., Fujioka T., Fulgenzi E. A., Garcia-Sobrino T., Garssen M. P. J., Georgios H. M., Gijsbers C. J., Gilchrist J. M., Gilhuis J., Giorli E., Goldstein J. M., Goyal N. A., Granit V., Grapperon A., Gutierrez G., Hadden R. D. M., Holbech J. V., Holt J. K. L., Pedret C. H., Htut M., Jellema K., Pascual I. J., Jimeno-Montero M. C., Kaida K., Karafiath S., Katzberg H. D., Kiers L., Kieseier B. C., Kimpinski K., Kleyweg R. P., Kokubun N., Kolb N. A., Kuitwaard K., Kuwabara S., Kwan J. Y., Ladha S. S., Lassen L. L., Lawson V., Ledingham D., Lucy S. T., Lunn M. P. T., Magot A., Manji H., Marchesoni C., Marfia G. A., Infante C. M., Hernandez E. M., Mataluni G., Mattiazi M., McDermott C. J., Meekins G. D., Miller J. A. L., Moris de la Tassa G., Physiotherapist J. M., Nascimbene C., Nowak R. J., Balaguer P. O., Osei-Bonsu M., Pan E. B. L., Pardal A. M., Pardo J., Pasnoor M., Pulley M., Rajabally Y. A., Rinaldi S., Ritter C., Roberts R. C., Rojas-Marcos I., Rudnicki S. A., Ruiz M., Sachs G. M., Samijn J. P. A., Santoro L., Savransky A., Schenone A., Schwindling L., Tous M. J. S., Sekiguchi Y., Sheikh K. A., Silvestri N. J., Sindrup S. H., Sommer C. L., Stein B., Stino A. M., Spyropoulos A., Srinivasan J., Styliani R., Suzuki H., Tankisi H., Tigner D., Twydell P., Van Damme P., Van der Kooi A. J., Van Dijk G. W., Van der Ree T., Van Koningsveld R., Valzania F., Varrato J. D., Vermeij F. H., Verschuuren J., Visser L. H., Vytopil M. V., Wilken M., Wilkerson C., Wirtz P. W., Yamagishi Y., Zhou L., Zivkovic S. A., Verboon, C, Doets, A, Galassi, G, Davidson, A, Waheed, W, Pereon, Y, Shahrizaila, N, Kusunoki, S, Lehmann, H, Harbo, T, Monges, S, Van Den Bergh, P, Willison, H, Cornblath, D, Jacobs, B, Hughes, R, Gorson, K, Hartung, H, Van Doorn, P, Van den Berg, B, Roodbol, J, Van Woerkom, M, Reisin, R, Reddel, S, Islam, Z, Islam, B, Mohammad, Q, Feasby, T, Dardiotis, E, Nobile-Orazio, E, Bateman, K, Illa, I, Querol, L, Hsieh, S, Chavada, G, Addington, J, Ajroud-Driss, S, Andersen, H, Antonini, G, Ariatti, A, Attarian, S, Badrising, U, Barroso, F, Benedetti, L, Beronio, A, Bianco, M, Binda, D, Briani, C, Bunschoten, C, Burmann, J, Bella, I, Bertorini, T, Bhavaraju-Sanka, R, Brannagan, T, Busby, M, Butterworth, S, Casasnovas, C, Cavaletti, G, Chao, C, Chen, S, Chetty, S, Claeys, K, Conti, M, Cosgrove, J, Dalakas, M, Demichelis, C, Derejko, M, Dillmann, U, Dimachkie, M, Doppler, K, Dornonville de la Cour, C, Echaniz-Laguna, A, Eftimov, F, Faber, C, Fazio, R, Fokke, C, Fujioka, T, Fulgenzi, E, Garcia-Sobrino, T, Garssen, M, Georgios, H, Gijsbers, C, Gilchrist, J, Gilhuis, J, Giorli, E, Goldstein, J, Goyal, N, Granit, V, Grapperon, A, Gutierrez, G, Hadden, R, Holbech, J, Holt, J, Pedret, C, Htut, M, Jellema, K, Pascual, I, Jimeno-Montero, M, Kaida, K, Karafiath, S, Katzberg, H, Kiers, L, Kieseier, B, Kimpinski, K, Kleyweg, R, Kokubun, N, Kolb, N, Kuitwaard, K, Kuwabara, S, Kwan, J, Ladha, S, Lassen, L, Lawson, V, Ledingham, D, Lucy, S, Lunn, M, Magot, A, Manji, H, Marchesoni, C, Marfia, G, Infante, C, Hernandez, E, Mataluni, G, Mattiazi, M, Mcdermott, C, Meekins, G, Miller, J, Moris de la Tassa, G, Physiotherapist, J, Nascimbene, C, Nowak, R, Balaguer, P, Osei-Bonsu, M, Pan, E, Pardal, A, Pardo, J, Pasnoor, M, Pulley, M, Rajabally, Y, Rinaldi, S, Ritter, C, Roberts, R, Rojas-Marcos, I, Rudnicki, S, Ruiz, M, Sachs, G, Samijn, J, Santoro, L, Savransky, A, Schenone, A, Schwindling, L, Tous, M, Sekiguchi, Y, Sheikh, K, Silvestri, N, Sindrup, S, Sommer, C, Stein, B, Stino, A, Spyropoulos, A, Srinivasan, J, Styliani, R, Suzuki, H, Tankisi, H, Tigner, D, Twydell, P, Van Damme, P, Van der Kooi, A, Van Dijk, G, Van der Ree, T, Van Koningsveld, R, Valzania, F, Varrato, J, Vermeij, F, Verschuuren, J, Visser, L, Vytopil, M, Wilken, M, Wilkerson, C, Wirtz, P, Yamagishi, Y, Zhou, L, Zivkovic, S, Verboon C., Doets A. Y., Galassi G., Davidson A., Waheed W., Pereon Y., Shahrizaila N., Kusunoki S., Lehmann H. C., Harbo T., Monges S., Van Den Bergh P., Willison H. J., Cornblath D. R., Jacobs B. C., Hughes R. A. C., Gorson K. C., Hartung H. P., Van Doorn P. A., Van den Berg B., Roodbol J., Van Woerkom M., Reisin R. C., Reddel S. W., Islam Z., Islam B., Mohammad Q. D., Feasby T. E., Dardiotis E., Nobile-Orazio E., Bateman K., Illa I., Querol L., Hsieh S. T., Chavada G., Addington J. M., Ajroud-Driss S., Andersen H., Antonini G., Ariatti A., Attarian S., Badrising U. A., Barroso F. A., Benedetti L., Beronio A., Bianco M., Binda D., Briani C., Bunschoten C., Burmann J., Bella I. R., Bertorini T. E., Bhavaraju-Sanka R., Brannagan T. H., Busby M., Butterworth S., Casasnovas C., Cavaletti G., Chao C. C., Chen S., Chetty S., Claeys K. G., Conti M. E., Cosgrove J. S., Dalakas MC., Demichelis C., Derejko M. A., Dillmann U., Dimachkie M. M., Doppler K., Dornonville de la Cour C., Echaniz-Laguna A., Eftimov F., Faber C. G., Fazio R., Fokke C., Fujioka T., Fulgenzi E. A., Garcia-Sobrino T., Garssen M. P. J., Georgios H. M., Gijsbers C. J., Gilchrist J. M., Gilhuis J., Giorli E., Goldstein J. M., Goyal N. A., Granit V., Grapperon A., Gutierrez G., Hadden R. D. M., Holbech J. V., Holt J. K. L., Pedret C. H., Htut M., Jellema K., Pascual I. J., Jimeno-Montero M. C., Kaida K., Karafiath S., Katzberg H. D., Kiers L., Kieseier B. C., Kimpinski K., Kleyweg R. P., Kokubun N., Kolb N. A., Kuitwaard K., Kuwabara S., Kwan J. Y., Ladha S. S., Lassen L. L., Lawson V., Ledingham D., Lucy S. T., Lunn M. P. T., Magot A., Manji H., Marchesoni C., Marfia G. A., Infante C. M., Hernandez E. M., Mataluni G., Mattiazi M., McDermott C. J., Meekins G. D., Miller J. A. L., Moris de la Tassa G., Physiotherapist J. M., Nascimbene C., Nowak R. J., Balaguer P. O., Osei-Bonsu M., Pan E. B. L., Pardal A. M., Pardo J., Pasnoor M., Pulley M., Rajabally Y. A., Rinaldi S., Ritter C., Roberts R. C., Rojas-Marcos I., Rudnicki S. A., Ruiz M., Sachs G. M., Samijn J. P. A., Santoro L., Savransky A., Schenone A., Schwindling L., Tous M. J. S., Sekiguchi Y., Sheikh K. A., Silvestri N. J., Sindrup S. H., Sommer C. L., Stein B., Stino A. M., Spyropoulos A., Srinivasan J., Styliani R., Suzuki H., Tankisi H., Tigner D., Twydell P., Van Damme P., Van der Kooi A. J., Van Dijk G. W., Van der Ree T., Van Koningsveld R., Valzania F., Varrato J. D., Vermeij F. H., Verschuuren J., Visser L. H., Vytopil M. V., Wilken M., Wilkerson C., Wirtz P. W., Yamagishi Y., Zhou L., and Zivkovic S. A.

Abstract

ObjectiveTo define the current treatment practice of Guillain-Barré syndrome (GBS).MethodsThe study was based on prospective observational data from the first 1,300 patients included in the International GBS Outcome Study. We described the treatment practice of GBS in general, and for (1) severe forms (unable to walk independently), (2) no recovery after initial treatment, (3) treatment-related fluctuations, (4) mild forms (able to walk independently), and (5) variant forms including Miller Fisher syndrome, taking patient characteristics and hospital type into account.ResultsWe excluded 88 (7%) patients because of missing data, protocol violation, or alternative diagnosis. Patients from Bangladesh (n = 189, 15%) were described separately because 83% were not treated. IV immunoglobulin (IVIg), plasma exchange (PE), or other immunotherapy was provided in 941 (92%) of the remaining 1,023 patients, including patients with severe GBS (724/743, 97%), mild GBS (126/168, 75%), Miller Fisher syndrome (53/70, 76%), and other variants (33/40, 83%). Of 235 (32%) patients who did not improve after their initial treatment, 82 (35%) received a second immune modulatory treatment. A treatment-related fluctuation was observed in 53 (5%) of 1,023 patients, of whom 36 (68%) were re-treated with IVIg or PE.ConclusionsIn current practice, patients with mild and variant forms of GBS, or with treatment-related fluctuations and treatment failures, are frequently treated, even in absence of trial data to support this choice. The variability in treatment practice can be explained in part by the lack of evidence and guidelines for effective treatment in these situations.

Published
2019

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

Author

Merkies, Ingemar S. J., van Schaik, Ivo N., Léger, 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, Björn, 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., Masson, G. Le, 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., Infante, C. Marquez, Benitez, S., Lunn, M., Morrow, J., Gosal, D., Lavin, T., Melamed, I., Testori, A., Ajroud-Driss, S., Menichella, D., Simpson, E., 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., Robberecht, W., Franques, J., Léger, J. -M., Morales, R. Juntas, Nguento, A., Schrey, Ch., Kamienowski, J., Stelmasiak, Z., Zwolińska, G., Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, CSL Behring, Neurologian yksikkö, Clinicum, Department of Food and Nutrition, and HUS Neurocenter

Subjects
Research Report, Male, Outcome Assessment, efficacy, Medizin, Chronic inflammatory demyelinating polyneuropathy, CIDP, IVIG, PATH, PRIMA, Neuroscience (all), Neurology (clinical), INFLAMMATORY DEMYELINATING POLYNEUROPATHY, 3124 Neurology and psychiatry, law.invention, Grip strength, 0302 clinical medicine, Randomized controlled trial, law, Interquartile range, hemic and lymphatic diseases, Outcome Assessment, Health Care, 80 and over, Medicine and Health Sciences, Prospective Studies, Chronic Inflammatory Demyelinating, Prospective cohort study, Aged, 80 and over, education.field_of_study, General Neuroscience, Immunoglobulins, Intravenous, Middle Aged, OPEN-LABEL, humanities, 3. Good health, PREVALENCE, Europe, 030220 oncology & carcinogenesis, Cohort, POLYRADICULONEUROPATHY, Female, Intravenous, Polyneuropathy, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Efficacy, Neuroscience(all), Population, Clinical Neurology, Immunoglobulins, MAINTENANCE TREATMENT, 03 medical and health sciences, Young Adult, Double-Blind Method, Internal medicine, medicine, Journal Article, Humans, Immunologic Factors, INTRAVENOUS IMMUNOGLOBULIN, Aged, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, education, Science & Technology, business.industry, Neurosciences, 3112 Neurosciences, Research Reports, medicine.disease, PHASE-III, Health Care, cidp, ivig, path, prima, Neurosciences & Neurology, business, 030217 neurology & neurosurgery
Abstract

PRIMA Trial Investigators and the PATH Study Group., 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)‐naïve 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

8. Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial

Author

Diaz-Manera, J, Kishnani, PS, Kushlaf, H, Ladha, S, Mozaffar, T, Straub, V, Toscano, A, Van der Ploeg, AT, Berger, KI, Clemens, PR, Chien, YH, Day, JW, Illarioshkin, S, Roberts, M, Attarian, S, Borges, JL, Bouhour, F, Choi, YC, Erdem-Ozdamar, S, Goker-Alpan, O, Kostera-Pruszczyk, A, Haack, KA, Hug, C, Huynh-Ba, O, Johnson, J, Thibault, N, Zhou, TY, Dimachkie, MM, and Schoser, B

Abstract

Background Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid ti-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphatereceptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late -onset Pompe disease. Methods We did a randomised, double-blind, phase 3 trial at 55 sites in 20 countries. We enrolled individuals (aged years) with enzymatically confirmed late-onset Pompe disease who had never received treatment. We used a centralised treatment allocation system to randomly allocate participants to either avalglucosidase alfa or alglucosidase alfa. Participants and investigators were unaware of their treatment allocation. The primary outcome measure was change from baseline to week 49 in upright forced vital capacity percent (FVC%) predicted. We used a hierarchical fixed sequential testing strategy, whereby non -inferiority of avalglucosidase alfa compared with alglucosidase alfa was assessed first, with a non-inferiority margin of 1.1. If non-inferiority was seen, then superiority was tested with a 5% significance level. The key secondary objective was effect on functional endurance, measured by the 6-minute walk test (6MWT). Safety was assessed, including treatment-emergent adverse events and infusion-associated reactions. The modified intent-to -treat population was the primary analysis population for all efficacy analyses. The safety population was the analysis population for safety analyses. This trial is registered with ClinicalTrials.gov, NCT02782741. We report results of the 49 -week primary analysis period. Findings Between Nov 2, 2016, and March 29, 2019, 100 participants were randomly allocated avalglucosidase alfa (n=51) or alglucosidase alfa (n=49). Treatment with avalglucosidase alfa resulted in a least-squares mean improvement in upright FVC% predicted of 2.89% (S E 0.88) compared with 0.46% (0.93) with alglucosidase alfa at week 49 (difference 2.43% [95% CI 0.13 to 4.99]). Non-inferiority was shown because the lower bound of the 95% CI for the difference far exceeded the predefined non -inferiority margin but did not exclude 0 (p=0. 0074). Superiority was not reached (p=0. 063), so formal testing was stopped, as per the testing hierarchy. Improvements were also seen in the 6MWT with avalglucosidase alfa compared with alglucosidase alfa, with greater increases in distance covered (difference 3001 in [95% CI 1.33 to 58.69]) and percent predicted (4.71% [0. 25 to 9.17]). Treatment-emergent adverse events potentially related to treatment were reported in 23 (45%) of 51 participants in the avalglucosidase alfa group and in 24 (49%) of 49 in the alglucosidase alfa group, and infusion-associated reactions were reported in 13 (26%) participants in the avalglucosidase alfa group and 16 (33%) in the alglucosidase alfa group. Of the five trial withdrawals, all in the alglucosidase alfa group, four were due to adverse events, including two infusion-associated reactions. Serious treatment-emergent adverse events were reported in eight (16%) participants who received avalglucosidase alfa and in 12 (25%) who received alglucosidase alfa. One participant treated with alglucosidase alfa died because of acute myocardial infarction determined to be unrelated to treatment. Antidrug antibody responses were similar in both groups. High and persistent titres W.2 800) and neutralising antibodies were more common with alglucosidase alfa (in 16 [33%] participants) than with avalglucosidase alfa (ten [20%]). Interpretation We consider that this study provides evidence ofclinically meaningful improvement with avalglucosida se alfa therapy over alglucosidase alfa in respiratory function, ambulation, and functional endurance, with no new safety signals reported. An open-label extended -treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa, with the aim for this therapy to become the new standard treatment in late-onset Pompe disease.

Published
2021

9. Intravenous immunoglobulin treatment for mild Guillain-Barré syndrome. An international observational study

Author

Verboon, C., Harbo, T., Cornblath, D. R., Hughes, R. A. C., Van Doorn, P. A., Lunn, M. P., Gorson, K. C., Barroso, F., Kuwabara, S., Galassi, G., Lehmann, H. C., Kusunoki, S., Reisin, R. C., Binda, D., Cavaletti, G., Andersen, Jacobs B. C. H., PhD (Aarhus University Hospital, Aarhus, Denmark), Attarian, S., PhD (CHU Timone, Marseille, France), Badrising, U. A., PhD (Leiden University Medical Centre, Leiden, The, Netherlands), Bateman, K., PhD (Groote Schuur Hospital, Cape, Town, South-Africa), Benedetti, L., PhD (Ospedale Sant’ Andrea La Spezia, Spezia, La, Italy), van den Berg, B., MD (Franciscus Gasthuis, Rotterdam, Van den Bergh, P., Luc, PhD (University Clinic St., Leuven, Belgium), Bertorini, T. E., MD (The University of Tennessee Health Science Center (UTHSC), Memphis, USA), Bhavaraju-Sanka, R., MD (University Hospital/ University of Texas Health Science Center, San Antonio Texas, USA), Bianco (Milan University, M., Humanitas Clinicala and Research Institute Milan, Briani, C., MD (University of Padova, Padova, Italy), Bürmann, J., MD (Universitätsklinikum des Saarlandes, Homburg, Germany), Casasnovas, C., Ciberer, PhD (Bellvitge University Hospital - IDIBELL Neurometabolic Diseases Group., Barcelona, Spain), Chao, C. C., PhD (National Taiwan University Hospital, Taipei, Taiwan), Chavada, G., PhD (Glasgow University, Glasgow, UK), Claeys, K. G., University Hospitals Leuven, PhD (1., Leuven, Belgium, KU Leuven, 2., Cosgrove, J. S., MD (Leeds General Infirmary, Leeds, UK), Dalakas, M. C., Thomas Jefferson University, MD (1., Philadelphia, Usa, National and Kapodistrian University of Athens, 2., Athens, Greece), Davidson, A., MD (University of Glasgow, van Dijk, G. W., MD (Canisius Wilhelmina Hospital, Nijmegen, Dardiotis, E., MD (University of Thessaly, Hospital of Larissa, Larissa, Greece), Derejko, M., MD (Odense University Hospital, Odense, Denmark), Dimachkie, M. M., MD (University of Kansas Medical Center, Kansas, City, Dornonville de la Cour, C., MD (National Hospital Copenhagen, Copenhagen, Denmark), Echaniz-Laguna, A., MD (Bicêtre University Hospital, Paris, France), Eftimov, F., PhD (Amsterdam University Medical Centre, Amsterdam, Faber, C. G., PhD (Maastricht University Medical Centre, Maastricht, Fazio, R., MD (Scientific Institute San Raffaele, Milan, Italy), Fulgenzi, J. Fehmi (University of Oxford E. A., MD (Hospital Cesar Milstein Buenos Aires, Buenos, Aires, Argentina), García-Sobrino, T., MD (Hospital Clínico de Santiago, Santiago de Compostela (A Coruña), Spain), Gijsbers, C. J., MD (Vlietland Hospital, Schiedam, Granit, V., MD (Montefiore Medical, Center, New, York, Grisanti, S., MD (Ospedale Sant’ Andrea La Spezia, Gutiérrez-Gutiérrez, G., MD (Hospital Universitario Infanta Sofia, San, Sebastian, Holbech, J. V., PhD (Odense University Hospital, Holt, J. K. L., Phd, FRCP (The Walton Centre, Liverpool, UK), Homedes, C., Ciberer, MD (Bellvitge University Hospital - IDIBELL Neurometabolic Diseases Group., Islam, B., PhD (International Centre for Diarrhoeal Disease Research, Bangladesh, (icddr, Dhaka, b), Bangladesh), Islam, Z., Jahan, I., PhD candidate (International Centre for Diarrhoeal Disease Research, Jericó Pascual, I., PhD (Complejo Hospitalario de Navarra, Pamplona, Spain), Karafiath, S., MD (University of Utah School of Medicine, Salt Lake City, Kerkhoff, H., PhD (Albert Schweitzer Hospital, Dordrecht, Kimpinski, K., MD (University Hospital, Lhsc, London-Ontario, Canada), Kohler, A., MD (Instituto de Investigaciones Neurológicas Raúl Carrea, Fleni, Kolb, N., MD (University of Vermont, Burlington, Vt, Kuitwaard, K., Albert Schweitzer Hospital, PhD (1., Erasmus MC, 2., Kuwahara, M., PhD (Kindai University, Osaka, Japan), Ladha, S. S., MD (Barrow Neurology Clinics, Phoenix, Arizona, Lee Pan, E., MBChB (Groote Schuur Hospital, Marfia, G. A., MD (Neurological Clinic, Policlinico Tor Vergata, Rome, Italy), Magot, A., MD (Reference Centre for NMD, Nantes University Hospital, France), Márquez Infante, C., MD (Hospital Universitario Virgen del Rocio, Seville, Spain), Martín-Aguilar, L., MD (Hospital de la Santa Creu, i Sant Pau, Universitat Autònoma de Barcelona, Martinez Hernandez, E., MD (Institut d’Investigacions Biomèdiques August Pi, i Sunyer (IDIBAPS), Hospital, Clinic, Mataluni, G., PhD (Neurological Clinic, Meekins, G., MD (University of Minnesota, Miller, J. A. L., PhD (Royal Victoria Infirmary, Newcastle, UK), Monges, M. S., Garrahan, MD (Hospital de Pediatría J. P., Nobile Orazio, E., PhD (Milan University, Pardal, A., MD (Hospital Britanico, Pardo Fernandez (Hospital Clínico de Santiago, J., Péréon, Y., PhD (Reference Centre for NMD, Pulley, M., MD (University of Florida, Jacksonville, USA), Querol Gutierrez, L., PhD (Hospital de la Santa Creu, i Sant Pau, Reddel, S. W., PhD (Concord Repatriation General Hospital, Sydney, Australia), van der Ree, T., (Westfriesgasthuis, Md, Hoorn, Rinaldi, S., Mbchb, Samijn, PhD (University of Oxford J. P. A., MD (Maasstad Hospital, Samukawa, M., Santoro, L., PhD (University Federico II, Napels, Italy), Savransky, A., Garrahan, PhD (Hospital de Pediatría J. P., Schwindling, L., Sedano Tous, M. J., MD (Hospital Universitario Marques de Valdecilla, Santander, Cantabria, Sekiguchi, Y., PhD (Chiba University, Chiba, Japan), Shahrizaila, N., MD (Neurology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Malaya), Silvestri, N. J., Sindrup, MD (Buffalo Jacobs School of Medicine S., Sommer, C. L., MD (Universitätsklinikum Würzburg, Würzburg, Germany), Spyropoulos (Royal Victoria Infirmary, A., Stein, B., Joseph’s Regional Medical Center, MD (St., Paterson, USA), Tan, C. Y., MRCP (Neurology Unit, Tankisi, H., Vermeij, F., Vytopil, M. V., Wirtz, PhD (Tufts University School of Medicine Lahey Hospital P. W., Phd, (HagaZiekenhuis, The, Hague, Waheed, W., MD (University of Vermont Medical Center, Burlington, Addington, USA). Other collaborators were:J. M., MD (University of Virginia, Charlottesville, USA), Ajroud-Driss, S., MD (Northwestern University Feinberg, Chicago, USA), Antonini, G., MD (Mental Health and Sensory Organs (NESMOS), Sapienza, University, Sant’Andrea, Hospital, Bella, I. R., MD (University of Mass Medical School, Worcester, USA), Brannagan, T. H., MD (Columbia University, New York City, Bunschoten, C., PhD candidate (Erasmus University Medical Centre, Busby, M., Bradford, UK), Butterworth, S., MD (Pinderfields Hospital, Wakefield, UK), Conti, M. E., MD (University Hospital Clinicas, Chen, S., Phd, (Rutgers, Robert Wood Johnson University Hospital, New, Brunswick, Doets, A., Feasby, T. E., MD (University of Calgary, Calgary, Canada), Fokke, C., MD (Gelre Hospital, Zutphen and Apeldoorn, Fujioka, T., MD (Toho University Medical Center, Tokyo, Japan), Garssen, M. P. J., PhD (Jeroen Bosch Hospital, Hertogenbosch, ’S, Gilchrist, J. M., MD (Soulthern Illinois University School of Medicine, Springfield, USA), Gilhuis, J., PhD (Reinier de Graaf Gasthuis, Delft, Goldstein, J. M., MD (Yale University School of Medicine, New, Haven, Goyal, N. A., MD (University of California, Irvine, USA), Hadden, R. D. M., PhD (King’s College Hospital, London, UK), Hsieh, S. T., Htut, M., George’s Hospital, MD (St., Illa, I., Jellema, K., PhD (Haaglanden Medisch Centrum, Kaida, K., PhD (National Defense Medical College, Saitama, Japan), Katzberg, H. D., MD (University of Toronto, Toronto, Canada), Kiers, L., MD (University of Melbourne, Royal Melbourne Hospital, Parkville, Australia), Kokubun, N., MD (Dokkyo Medical University, Tochigi, Japan), van Koningsveld, R., PhD (Elkerliek Hospital, Helmond and Deurne, van der Kooi, A. J., Kwan, J. Y., MD (University of Maryland School of Medicine, Baltimore, USA), Landschoff Lassen, L., MD (Glostrup Hospital, Glostrup, Denmark), Lawson, V., MD (Wexner Medical Center at The Ohio State University, Columbus, USA), Leonhard, S. E., Mandarakas, M., PhD (Erasmus University Medical Centre, Manji, H., FRCP (Ipswich Hospital, Ipswich, UK), Mattiazzi, M. G., MD (Hospital Militar Central, Mcdermott, C. J., MD (Royal Hallamshire Hospital, Nihr, Clinical, Sheffield, UK), Mohammad, Q. D., PhD (National Institute of Neurosciences and Hospital, Dhaka, Bangladesh), Morís de la Tassa, G., MD (Hospital UniversitarioCentral de Asturias, Asturias, Spain), Nascimbene, C., PhD (Luigi Sacco Hospital, Niks, E. H., Nowak, R. J., Osei-Bonsu, M., PhD (James Cook University Hospital, Middlesbrough, UK), Pascuzzi, R. M., MD (University of Indiana School of Medicine, Indianapolis, USA), Roberts, R. C., MD (Addenbrooke’s Hospital Cambridge, Cambridge, UK), Rojas-Marcos, I., MD (Hospital Univesitario Reina Sofia, Cordoba, Spain), Roodbol, J., Rudnicki, S. A., MD (University of Arkansas, Fayetteville, USA), Sachs, G. M., MD (University of Rhode Island, Providence, USA), Schenone, A., Department of Neurosciences, PhD (1., Rehabilitation, Ophthalmology, Genetics and Maternal and Infantile Sciences (DINOGMI), University of Genova, Genova, IRCCS Policlinico San Martino, Italy 2., Genova, Italy), Sheikh, K., PhD (The University of Texas Health Science Center at Houston, Houston, USA), Twydell, P., DO (Spectrum Health System, Grand, Rapids, Van Damme, P., PhD (University Hospital Leuven, Varrato, J. D., DO (Lehigh Valley Health Network, Allentown, USA), Visser, L. H., PhD (Elisabeth-TweeSteden Hospital, Tilburg and Waalwijk, Willison, H. J., PhD (University of Glasgow, van Woerkom (Erasmus MC, M., Zhou, L., PhD (Icahn School, Verboon, C, Harbo, T, Cornblath, D, Hughes, R, Van Doorn, P, Lunn, M, Gorson, K, Barroso, F, Kuwabara, S, Galassi, G, Lehmann, H, Kusunoki, S, Reisin, R, Binda, D, Cavaletti, G, Jacobs, B, consortium, IGOS, consortium, GOS, Neurosurgery, Neurology, and Immunology

Subjects
Adult, Male, medicine.medical_specialty, intravenous immunoglobulins, DIAGNOSIS, Guillain-Barre Syndrome, Settore MED/26, DISEASE, Disease course, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, hemic and lymphatic diseases, Internal medicine, Clinical endpoint, medicine, Humans, In patient, guillain-barré syndrome, 030212 general & internal medicine, NEUROPATHIES, biology, Guillain-Barre syndrome, business.industry, Guillain-Barré syndrome (GBS), treatment, course, Confounding, Immunoglobulins, Intravenous, Middle Aged, medicine.disease, Confidence interval, Psychiatry and Mental health, Treatment Outcome, biology.protein, Female, Surgery, Observational study, Neurology (clinical), Antibody, business, 030217 neurology & neurosurgery
Abstract

ObjectiveTo compare the disease course in patients with mild Guillain-Barré syndrome (GBS) who were treated with intravenous immunoglobulin (IVIg) or supportive care only.MethodsWe selected patients from the prospective observational International GBS Outcome Study (IGOS) who were able to walk independently at study entry (mild GBS), treated with one IVIg course or supportive care. The primary endpoint was the GBS disability score four weeks after study entry, assessed by multivariable ordinal regression analysis.ResultsOf 188 eligible patients, 148 (79%) were treated with IVIg and 40 (21%) with supportive care. The IVIg group was more disabled at baseline. IVIg treatment was not associated with lower GBS disability scores at 4 weeks (adjusted OR (aOR) 1.62, 95% CI 0.63 to 4.13). Nearly all secondary endpoints showed no benefit from IVIg, although the time to regain full muscle strength was shorter (28 vs 56 days, p=0.03) and reported pain at 26 weeks was lower (n=26/121, 22% vs n=12/30, 40%, p=0.04) in the IVIg treated patients. In the subanalysis with persistent mild GBS in the first 2 weeks, the aOR for a lower GBS disability score at 4 weeks was 2.32 (95% CI 0.76 to 7.13). At 1 year, 40% of all patients had residual symptoms.ConclusionIn patients with mild GBS, one course of IVIg did not improve the overall disease course. The certainty of this conclusion is limited by confounding factors, selection bias and wide confidence limits. Residual symptoms were often present after one year, indicating the need for better treatments in mild GBS.

Published
2021

10. International Guillain-Barré Syndrome Outcome Study

Author

Jacobs, B, van den Berg, B, Verboon, C, Chavada, G, Cornblath, D, Gorson, K, Harbo, T, Hartung, H, Hughes, R, Kusunoki, S, van Doorn, P, Willison, H, Consortium, I, van Woerkom, M, Roodbol, J, Reisin, R, Reddel, S, Islam, Z, Islam, B, Mohammad, Q, van den Bergh, P, Feasby, T, Wang, Y, Péréon, Y, Lehmann, H, Dardiotis, E, Nobile Orazio, E, Shahrizaila, N, Bateman, K, Illa, I, Querol, L, Hsieh, S, Davidson, A, Addington, J, Ajroud Driss, S, Andersen, H, Antonini, G, Attarian, S, Badrising, U, Barroso, F, Benedetti, L, Beronio, A, Bianco, M, Binda, D, Briani, C, Bürmann, J, Bella, I, Bertorini, T, Bhavaraju Sanka, R, Brannagan, T, Busby, M, Butterworth, S, Campagnolo, M, Casasnovas, C, Cavaletti, G, Chao, C, Chen, S, Chetty, S, Claeys, K, Cohen, J, Conti, M, Cosgrove, J, Dalakas, M, Dimachkie, M, Dillmann, U, Domínguez González, C, Doppler, K, Dornonville de la Cour, C, Echaniz Laguna, A, Eftimov, F, Faber, C, Fazio, R, Fokke, C, Fujioka, T, Fulgenzi, E, Galassi, G, Garcia, T, Garnero, M, Garssen, M, Gijsbers, C, Gilchrist, J, Gilhuis, H, Goldstein, J, Goyal, N, Granit, V, Grapperon, A, Gutiérrez Gutiérrez, G, Gutmann, L, Hadden, R, Holbech, J, Holt, J, Homedes Pedret, C, Htut, M, Jellema, K, Jericó Pascual, I, Kaida, K, Karafiath, S, Katzberg, H, Kiers, L, Kieseier, B, Kimpinski, K, Kleyweg, R, Kokubun, N, Kolb, N, Kuitwaard, K, Kuwabara, S, Kwan, J, Ladha, S, Landschoff Lassen, L, Lawson, V, Ledingham, D, Léon Cejas, L, Luciano, C, Lucy, S, Lunn, M, Magot, A, Manji, H, Marchesoni, C, Marfia, Ga, Márquez Infante, C, Martinez Hernandez, E, Mataluni, G, Mattiazi, M, Mcdermott, C, Meekins, G, Miller, J, Monges, M, Montero, M, Morís de la Tassa, G, Nascimbene, C, Neumann, C, Nowak, R, Orizaola Balaguer, P, Osei Bonsu, M, Pan, E, Pardo Fernandez, J, Pasnoor, M, Pulley, M, Rajabally, Y, Rinaldi, S, Ritter, C, Roberts, R, Rojas Marcos, I, Rudnicki, S, Sachs, G, Samijn, J, Santoro, L, Saperstein, D, Savransky, A, Schneider, H, Schenone, A, Sedano Tous, M, Sekiguchi, Y, Sheikh, K, Silvestri, N, Sindrup, S, Sommer, C, Stein, B, Stino, A, Spyropoulos, A, Srinivasan, J, Suzuki, H, Taylor, S, Tankisi, H, Tigner, D, Twydell, P, Valzania, F, van Damme, P, van der Kooi, A, van Dijk, G, van der Ree, T, van Koningsveld, R, Varrato, J, Vermeij, F, Verschuuren, J, Visser, L, Vytopil, M, Waheed, W, Wilken, M, Wilkerson, C, Wirtz, P, Yamagishi, Y, Yiu, E, Zhou, L, Zivkovic, S, Immunology, Neurology, Jacobs, B, van den Berg, B, Verboon, C, Chavada, G, Cornblath, D, Gorson, K, Harbo, T, Hartung, H, Hughes, R, Kusunoki, S, van Doorn, P, Willison, H, van Woerkom, M, Roodbol, J, Reisin, R, Reddel, S, Islam, Z, Islam, B, Mohammad, Q, van den Bergh, P, Feasby, T, Wang, Y, Pã©rã©on, Y, Lehmann, H, Dardiotis, E, Nobile Orazio, E, Shahrizaila, N, Bateman, K, Illa, I, Querol, L, Hsieh, S, Davidson, A, Addington, J, Ajroud Driss, S, Andersen, H, Antonini, G, Attarian, S, Badrising, U, Barroso, F, Benedetti, L, Beronio, A, Bianco, M, Binda, D, Briani, C, Bã¼rmann, J, Bella, I, Bertorini, T, Bhavaraju Sanka, R, Brannagan, T, Busby, M, Butterworth, S, Campagnolo, M, Casasnovas, C, Cavaletti, G, Chao, C, Chen, S, Chetty, S, Claeys, K, Cohen, J, Conti, M, Cosgrove, J, Dalakas, M, Dimachkie, M, Dillmann, U, Domínguez González, C, Doppler, K, Dornonville de la Cour, C, Echaniz Laguna, A, Eftimov, F, Faber, C, Fazio, R, Fokke, C, Fujioka, T, Fulgenzi, E, Galassi, G, Garcia, T, Garnero, M, Garssen, M, Gijsbers, C, Gilchrist, J, Gilhuis, H, Goldstein, J, Goyal, N, Granit, V, Grapperon, A, Gutiérrez Gutiérrez, G, Gutmann, L, Hadden, R, Holbech, J, Holt, J, Homedes Pedret, C, Htut, M, Jellema, K, Jericó Pascual, I, Kaida, K, Karafiath, S, Katzberg, H, Kiers, L, Kieseier, B, Kimpinski, K, Kleyweg, R, Kokubun, N, Kolb, N, Kuitwaard, K, Kuwabara, S, Kwan, J, Ladha, S, Landschoff Lassen, L, Lawson, V, Ledingham, D, Léon Cejas, L, Luciano, C, Lucy, S, Lunn, M, Magot, A, Manji, H, Marchesoni, C, Marfia, G, Márquez Infante, C, Martinez Hernandez, E, Mataluni, G, Mattiazi, M, Mcdermott, C, Meekins, G, Miller, J, Monges, M, Montero, M, Morís de la Tassa, G, Nascimbene, C, Neumann, C, Nowak, R, Orizaola Balaguer, P, Osei Bonsu, M, Pan, E, Pardo Fernandez, J, Pasnoor, M, Pulley, M, Rajabally, Y, Rinaldi, S, Ritter, C, Roberts, R, Rojas Marcos, I, Rudnicki, S, Sachs, G, Samijn, J, Santoro, L, Saperstein, D, Savransky, A, Schneider, H, Schenone, A, Sedano Tous, M, Sekiguchi, Y, Sheikh, K, Silvestri, N, Sindrup, S, Sommer, C, Stein, B, Stino, A, Spyropoulos, A, Srinivasan, J, Suzuki, H, Taylor, S, Tankisi, H, Tigner, D, Twydell, P, Valzania, F, van Damme, P, van der Kooi, A, van Dijk, G, van der Ree, T, van Koningsveld, R, Varrato, J, Vermeij, F, Verschuuren, J, Visser, L, Vytopil, M, Waheed, W, Wilken, M, Wilkerson, C, Wirtz, P, Yamagishi, Y, Yiu, E, Zhou, L, Zivkovic, S, Rehabilitation medicine, Internal medicine, and ANS - Neuroinfection & -inflammation

Subjects
Male, Pediatrics, PROGNOSIS, diagnosis, International Cooperation, Guillain-Barré syndrome, biomarkers, outcome, prognosis, treatment, Guillain-Barre syndrome, Guillain-Barré syndrome, Neuroscience (all), Neurology (clinical), Cohort Studies, 0302 clinical medicine, Epidemiology, Outcome Assessment, Health Care, INFECTION, CRITERIA, 030212 general & internal medicine, General Neuroscience, Biobank, Observational Studies as Topic, diagnosi, Disease Progression, biomarker, Female, Settore MED/26 - Neurologia, medicine.symptom, prognosi, Cohort study, medicine.medical_specialty, Weakness, Guillain-Barre Syndrome, CLASSIFICATION, VALIDATION, 03 medical and health sciences, medicine, Humans, INTRAVENOUS IMMUNOGLOBULIN, Protocol (science), business.industry, Polyradiculoneuropathy, medicine.disease, ANTIBODIES, Observational study, business, COLLECTION, 030217 neurology & neurosurgery
Abstract

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within 2 weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course, and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1,000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1,400 participants from 143 active centers in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modeling, treatment effects, and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS.

Published
2017

12. Current treatment practice of Guillain-Barré syndrome

Author

Verboon C., Doets A. Y., Galassi G., Davidson A., Waheed W., Pereon Y., Shahrizaila N., Kusunoki S., Lehmann H. C., Harbo T., Monges S., Van Den Bergh P., Willison H. J., Cornblath D. R., Jacobs B. C., Hughes R. A. C., Gorson K. C., Hartung H. P., Van Doorn P. A., Van den Berg B., Roodbol J., Van Woerkom M., Reisin R. C., Reddel S. W., Islam Z., Islam B., Mohammad Q. D., Feasby T. E., Dardiotis E., Nobile-Orazio E., Bateman K., Illa I., Querol L., Hsieh S. T., Chavada G., Addington J. M., Ajroud-Driss S., Andersen H., Antonini G., Ariatti A., Attarian S., Badrising U. A., Barroso F. A., Benedetti L., Beronio A., Bianco M., Binda D., Briani C., Bunschoten C., Burmann J., Bella I. R., Bertorini T. E., Bhavaraju-Sanka R., Brannagan T. H., Busby M., Butterworth S., Casasnovas C., Cavaletti G., Chao C. C., Chen S., Chetty S., Claeys K. G., Conti M. E., Cosgrove J. S., Dalakas MC., Demichelis C., Derejko M. A., Dillmann U., Dimachkie M. M., Doppler K., Dornonville de la Cour C., Echaniz-Laguna A., Eftimov F., Faber C. G., Fazio R., Fokke C., Fujioka T., Fulgenzi E. A., Garcia-Sobrino T., Garssen M. P. J., Georgios H. M., Gijsbers C. J., Gilchrist J. M., Gilhuis J., Giorli E., Goldstein J. M., Goyal N. A., Granit V., Grapperon A., Gutierrez G., Hadden R. D. M., Holbech J. V., Holt J. K. L., Pedret C. H., Htut M., Jellema K., Pascual I. J., Jimeno-Montero M. C., Kaida K., Karafiath S., Katzberg H. D., Kiers L., Kieseier B. C., Kimpinski K., Kleyweg R. P., Kokubun N., Kolb N. A., Kuitwaard K., Kuwabara S., Kwan J. Y., Ladha S. S., Lassen L. L., Lawson V., Ledingham D., Lucy S. T., Lunn M. P. T., Magot A., Manji H., Marchesoni C., Marfia G. A., Infante C. M., Hernandez E. M., Mataluni G., Mattiazi M., McDermott C. J., Meekins G. D., Miller J. A. L., Moris de la Tassa G., Physiotherapist J. M., Nascimbene C., Nowak R. J., Balaguer P. O., Osei-Bonsu M., Pan E. B. L., Pardal A. M., Pardo J., Pasnoor M., Pulley M., Rajabally Y. A., Rinaldi S., Ritter C., Roberts R. C., Rojas-Marcos I., Rudnicki S. A., Ruiz M., Sachs G. M., Samijn J. P. A., Santoro L., Savransky A., Schenone A., Schwindling L., Tous M. J. S., Sekiguchi Y., Sheikh K. A., Silvestri N. J., Sindrup S. H., Sommer C. L., Stein B., Stino A. M., Spyropoulos A., Srinivasan J., Styliani R., Suzuki H., Tankisi H., Tigner D., Twydell P., Van Damme P., Van der Kooi A. J., Van Dijk G. W., Van der Ree T., Van Koningsveld R., Valzania F., Varrato J. D., Vermeij F. H., Verschuuren J., Visser L. H., Vytopil M. V., Wilken M., Wilkerson C., Wirtz P. W., Yamagishi Y., Zhou L., Zivkovic S. A., Neurology, AII - Infectious diseases, AII - Inflammatory diseases, ANS - Neuroinfection & -inflammation, Immunology, Erasmus MC other, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, Verboon, C, Doets, A, Galassi, G, Davidson, A, Waheed, W, Pereon, Y, Shahrizaila, N, Kusunoki, S, Lehmann, H, Harbo, T, Monges, S, Van Den Bergh, P, Willison, H, Cornblath, D, Jacobs, B, Hughes, R, Gorson, K, Hartung, H, Van Doorn, P, Van den Berg, B, Roodbol, J, Van Woerkom, M, Reisin, R, Reddel, S, Islam, Z, Islam, B, Mohammad, Q, Feasby, T, Dardiotis, E, Nobile-Orazio, E, Bateman, K, Illa, I, Querol, L, Hsieh, S, Chavada, G, Addington, J, Ajroud-Driss, S, Andersen, H, Antonini, G, Ariatti, A, Attarian, S, Badrising, U, Barroso, F, Benedetti, L, Beronio, A, Bianco, M, Binda, D, Briani, C, Bunschoten, C, Burmann, J, Bella, I, Bertorini, T, Bhavaraju-Sanka, R, Brannagan, T, Busby, M, Butterworth, S, Casasnovas, C, Cavaletti, G, Chao, C, Chen, S, Chetty, S, Claeys, K, Conti, M, Cosgrove, J, Dalakas, M, Demichelis, C, Derejko, M, Dillmann, U, Dimachkie, M, Doppler, K, Dornonville de la Cour, C, Echaniz-Laguna, A, Eftimov, F, Faber, C, Fazio, R, Fokke, C, Fujioka, T, Fulgenzi, E, Garcia-Sobrino, T, Garssen, M, Georgios, H, Gijsbers, C, Gilchrist, J, Gilhuis, J, Giorli, E, Goldstein, J, Goyal, N, Granit, V, Grapperon, A, Gutierrez, G, Hadden, R, Holbech, J, Holt, J, Pedret, C, Htut, M, Jellema, K, Pascual, I, Jimeno-Montero, M, Kaida, K, Karafiath, S, Katzberg, H, Kiers, L, Kieseier, B, Kimpinski, K, Kleyweg, R, Kokubun, N, Kolb, N, Kuitwaard, K, Kuwabara, S, Kwan, J, Ladha, S, Lassen, L, Lawson, V, Ledingham, D, Lucy, S, Lunn, M, Magot, A, Manji, H, Marchesoni, C, Marfia, G, Infante, C, Hernandez, E, Mataluni, G, Mattiazi, M, Mcdermott, C, Meekins, G, Miller, J, Moris de la Tassa, G, Physiotherapist, J, Nascimbene, C, Nowak, R, Balaguer, P, Osei-Bonsu, M, Pan, E, Pardal, A, Pardo, J, Pasnoor, M, Pulley, M, Rajabally, Y, Rinaldi, S, Ritter, C, Roberts, R, Rojas-Marcos, I, Rudnicki, S, Ruiz, M, Sachs, G, Samijn, J, Santoro, L, Savransky, A, Schenone, A, Schwindling, L, Tous, M, Sekiguchi, Y, Sheikh, K, Silvestri, N, Sindrup, S, Sommer, C, Stein, B, Stino, A, Spyropoulos, A, Srinivasan, J, Styliani, R, Suzuki, H, Tankisi, H, Tigner, D, Twydell, P, Van Damme, P, Van der Kooi, A, Van Dijk, G, Van der Ree, T, Van Koningsveld, R, Valzania, F, Varrato, J, Vermeij, F, Verschuuren, J, Visser, L, Vytopil, M, Wilken, M, Wilkerson, C, Wirtz, P, Yamagishi, Y, Zhou, L, and Zivkovic, S

Subjects
Adult, medicine.medical_specialty, Adolescent, Patient characteristics, PLASMA-EXCHANGE, 030204 cardiovascular system & hematology, Guillain-Barre Syndrome, Settore MED/26, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Severity of illness, Medicine, Effective treatment, INTRAVENOUS IMMUNOGLOBULIN, Humans, Prospective Studies, Child, Child, Preschool, Treatment Outcome, Prospective cohort study, Preschool, Guillain-Barre syndrome, business.industry, medicine.disease, RANDOMIZED-TRIAL, Prospective Studie, Hospital treatment, Treatment practice, Observational study, Neurology (clinical), business, 030217 neurology & neurosurgery, Human
Abstract

ObjectiveTo define the current treatment practice of Guillain-Barré syndrome (GBS).MethodsThe study was based on prospective observational data from the first 1,300 patients included in the International GBS Outcome Study. We described the treatment practice of GBS in general, and for (1) severe forms (unable to walk independently), (2) no recovery after initial treatment, (3) treatment-related fluctuations, (4) mild forms (able to walk independently), and (5) variant forms including Miller Fisher syndrome, taking patient characteristics and hospital type into account.ResultsWe excluded 88 (7%) patients because of missing data, protocol violation, or alternative diagnosis. Patients from Bangladesh (n = 189, 15%) were described separately because 83% were not treated. IV immunoglobulin (IVIg), plasma exchange (PE), or other immunotherapy was provided in 941 (92%) of the remaining 1,023 patients, including patients with severe GBS (724/743, 97%), mild GBS (126/168, 75%), Miller Fisher syndrome (53/70, 76%), and other variants (33/40, 83%). Of 235 (32%) patients who did not improve after their initial treatment, 82 (35%) received a second immune modulatory treatment. A treatment-related fluctuation was observed in 53 (5%) of 1,023 patients, of whom 36 (68%) were re-treated with IVIg or PE.ConclusionsIn current practice, patients with mild and variant forms of GBS, or with treatment-related fluctuations and treatment failures, are frequently treated, even in absence of trial data to support this choice. The variability in treatment practice can be explained in part by the lack of evidence and guidelines for effective treatment in these situations.

Published
2019

13. Phase 1–2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS

Author

Miller, T., Cudkowicz, M., Shaw, P.J., Andersen, P.M., Atassi, N., Bucelli, R.C., Genge, A., Glass, J., Ladha, S., Ludolph, A.L., Maragakis, N.J., McDermott, C.J., Pestronk, A., Ravits, J., Salachas, F., Trudell, R., Van Damme, P., Zinman, L., Bennett, C.F., Lane, R., Sandrock, A., Runz, H., Graham, D., Houshyar, H., McCampbell, A., Nestorov, I., Chang, I., McNeill, M., Fanning, L., Fradette, S., and Ferguson, T.A.

Abstract

BACKGROUND\ud \ud Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to SOD1 mutations.\ud \ud \ud METHODS\ud \ud We conducted a phase 1–2 ascending-dose trial evaluating tofersen in adults with ALS due to SOD1 mutations. In each dose cohort (20, 40, 60, or 100 mg), participants were randomly assigned in a 3:1 ratio to receive five doses of tofersen or placebo, administered intrathecally for 12 weeks. The primary outcomes were safety and pharmacokinetics. The secondary outcome was the change from baseline in the cerebrospinal fluid (CSF) SOD1 concentration at day 85. Clinical function and vital capacity were measured.\ud \ud \ud RESULTS\ud \ud A total of 50 participants underwent randomization and were included in the analyses; 48 participants received all five planned doses. Lumbar puncture–related adverse events were observed in most participants. Elevations in CSF white-cell count and protein were reported as adverse events in 4 and 5 participants, respectively, who received tofersen. Among participants who received tofersen, one died from pulmonary embolus on day 137, and one from respiratory failure on day 152; one participant in the placebo group died from respiratory failure on day 52. The difference at day 85 in the change from baseline in the CSF SOD1 concentration between the tofersen groups and the placebo group was 2 percentage points (95% confidence interval [CI], −18 to 27) for the 20-mg dose, −25 percentage points (95% CI, −40 to −5) for the 40-mg dose, −19 percentage points (95% CI, −35 to 2) for the 60-mg dose, and −33 percentage points (95% CI, −47 to −16) for the 100-mg dose.\ud \ud \ud CONCLUSIONS\ud \ud In adults with ALS due to SOD1 mutations, CSF SOD1 concentrations decreased at the highest concentration of tofersen administered intrathecally over a period of 12 weeks. CSF pleocytosis occurred in some participants receiving tofersen. Lumbar puncture–related adverse events were observed in most participants. (Funded by Biogen; ClinicalTrials.gov number, NCT02623699. opens in new tab; EudraCT number, 2015-004098-33. opens in new tab.)

Published
2020

14. Second IVIg course in Guillain-Barré syndrome with poor prognosis. The non-randomised ISID study

Author

Verboon, C., Van Den Berg, B., Cornblath, D. R., Venema, E., Gorson, K. C., Lunn, M. P., Lingsma, H., Van Den Bergh, P., Harbo, T., Bateman, K., Pereon, Y., Sindrup, So. H., Kusunoki, S., Miller, J., Islam, Z., Hartung, H. -P., Chavada, G., Jacobs, B. C., Hughes, R. A. C., Addington, Van Doorn P. A. J. M., MD (University of Virginia, Charlottesville, USA), on October 7, S. Consortia. Protected by copyright., Downloaded from 8 Verboon C, 2019 at Uppsala Universitet BIBSAM http://jnnp. bmj. com/ J Neurol Neurosurg Psychiatry: first published as 10. 1136/jnnp-2019-321496 on 5 October 2019., J Neurol Neurosurg Psychiatry 2019, et al., 1136/jnnp-2019-321496 Neuromuscular Ajroud-Driss, 0:1–9. doi:10., MD (Northwestern University Feinberg, Chicago, USA), Antonini, G., MD (Mental Health and Sensory Organs (NESMOS), Sapienza, University, Sant’Andrea, Hospital, Rome, Italy), Attarian, S., PhD (CHU Timone, Marseille, France), Barroso, F. A., MD (Instituto de Investigaciones Neurológicas Raúl Carrea, Fleni, Buenos, Aires, Argentina), Benedetti, L., PhD (Ospedale Sant’ Andrea La Spezia, Spezia, La, Italy), Bertorini, T. E., MD (The University of Tennessee Health Science Center (UTHSC), Memphis, USA), Brannagan, T. H., MD (Columbia University, New York City, USA), Briani, C., MD (University of Padova, Padova, Italy), Bhavaraju-Sanka, R., MD (University Hospital/University of Texas Health Science Center, San Antonio Texas, Butterworth, S., MD (Pinderfields Hospital, Wakefield, UK), Casasnovas, C., Ciberer, PhD (Bellvitge University Hospital – IDIBELL Neurometabolic Diseases Group., Barcelona, Spain), Cavaletti, G., MD (University Milano-Bicocca, Monza, Italy), Chen, S., Phd, (Rutgers, Robert Wood Johnson University Hospital, New, Brunswick, Claeys, K. G., University Hospitals Leuven, PhD (1., Leuven, Belgium, KU Leuven, 2., Leuven, Belgium), Cosgrove, J. S., MD (Leeds General Infirmary, Leeds, UK), Davidson, A., MD (University of Glasgow, Glasgow, UK), Dardiotis, E., MD (University of Thessaly, Hospital of Larissa, Larissa, Greece), Dornonville de la Cour, C., MD (National Hospital Copenhagen, Copenhagen, Denmark), Faber, C. G., PhD (Maastricht University Medical Centre, Maastricht, The, Netherlands), Feasby, T. E., MD (University of Calgary, Calgary, Canada), Fujioka, T., MD (Toho University Medical Center, Tokyo, Japan), Galassi, G., MD (University Hospital of Modena, Modena, Italy), Gilchrist, J. M., MD (Soulthern Illinois University School of Medicine, Springfield, USA), Goyal, N. A., MD (University of California, Irvine, USA), Granit, V., MD (Montefiore Medical, Center, New, York, Gutiérrez-Gutiérrez, G., MD (Hospital Universitario Infanta Sofia, San, Sebastian, Spain), Hadden, R. D. M., PhD (King’s College Hospital, London, UK), Holt, J. K. L., Phd, FRCP (The Walton Centre, Liverpool, UK), Htut, M., George’s Hospital, MD (St., Jericó Pascual, I., PhD (Complejo Hospitalario de Navarra, Pamplona, Spain), Karafiath, S., MD (University of Utah School of Medicine, Salt Lake City, Katzberg, H. D., MD (University of Toronto, Toronto, Canada), Kiers, L., MD (University of Melbourne, Royal Melbourne Hospital, Parkville, Australia), Kieseier, B. C., MD (Heinrich Heine University, Düsseldorf, Germany), Kimpinski, K., MD (University Hospital, Lhsc, London-Ontario, Canada), Kuwabara, S., PhD (Chiba University, Chiba, Japan), Kwan, J. Y., MD (University of Maryland School of Medicine, Baltimore, USA), Ladha, S. S., MD (Barrow Neurology Clinics, Phoenix, Arizona, Lawson, V., MD (Wexner Medical Center at The Ohio State University, Columbus, USA), Lehmann, H., PhD (University Hospital of Cologne, Universitätsklinikum, Köln, Cologne, Germany), Manji, H., FRCP (Ipswich Hospital, Ipswich, UK), Marfia, G. A., MD (Neurological Clinic, Policlinico Tor Vergata, Márquez Infante, C., MD (Hospital Universitario Virgen del Rocio, Seville, Spain), Mattiazzi, M. G., MD (Hospital Militar Central, Mcdermott, C. J., MD (Royal Hallamshire Hospital, Nihr, Clinical, Sheffield, UK), Monges, M. S., Garrahan, MD (Hospital de Pediatría J. P., Morís de la Tassa, G., MD (Hospital Universitario Central de Asturias, Asturias, Spain), Nascimbene, C., PhD (Luigi Sacco Hospital, Milan, Italy), Nobile Orazio, E., PhD (Milan University, Humanitas Clinicala and Research Institute Milan, Nowak, R. J., MD (Yale University School of Medicine, New, Haven, Osei-Bonsu (James Cook University Hospital, M., Middlesbrough, UK), Pardo Fernandez (Hospital Clínico de Santiago, J., Santiago de Compostela (A Coruña), Querol Gutierrez, L., PhD (Hospital de la Santa Creu, i Sant Pau, Universitat Autònoma de Barcelona, Reisin (Hospital Britanico, R., Rinaldi, S., Mbchb, Roberts, PhD (University of Oxford R. C., MD (Addenbrooke’s Hospital Cambridge, Cambridge, UK), Rojas-Marcos, I., MD (Hospital Univesitario Reina Sofia, Cordoba, Spain), Rudnicki, S. A., MD (University of Arkansas, Fayetteville, USA), Schenone, A., Department of Neurosciences, PhD (1., Rehabilitation, Ophthalmology, Genetics and Maternal and Infantile Sciences (DINOGMI), University of Genova, Genova, IRCCS Policlinico San Martino, Italy 2., Genova, Italy), Sedano Tous, M. J., MD (Hospital Universitario Marques de Valdecilla, Santander, Cantabria, Shahrizaila, N., MD (Neurology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Malaya), Sheikh, K., PhD (The University of Texas Health Science Center at Houston, Houston, USA), Silvestri, N. J., MD (Buffalo General Medical Center, Buffalo, Ny, Sommer, C. L., MD (Universitätsklinikum Würzburg, Würzburg, Germany), Varrato, J. D., DO (Lehigh Valley Health Network, Allentown, USA), Verschuuren, J., PhD (Leiden University Medical Centre, Leiden, Vytopil, M. V., Waheed, PhD (Tufts University School of Medicine Lahey Hospital W., MD (University of Vermont Medical Center, Burlington, USA), Zhou, L., PhD (Icahn School of Medicine at Mount Sinai, Badrising, USA). Other collaborators were:U. A., Bella, I. R., MD (University of Mass Medical School, Worcester, USA), Bunschoten, C., PhD candidate (Erasmus University Medical Centre, Rotterdam, Bürmann, J., Universitätsklinikum des Saarlandes, Homburg, Germany), Busby, M., Bradford, UK), Chao, C. C., PhD (National Taiwan University Hospital, Taipei, Taiwan), Conti, M. E., MD (University Hospital Clinicas, Dalakas, M. C., Thomas Jefferson University, MD (1., Philadelphia, Usa, National and Kapodistrian University of Athens, 2., Athens, Greece), Van Damme, P., PhD (University Hospital Leuven, Doets, A., van Dijk, G. W., MD (Canisius Wilhelmina Hospital, Nijmegen, Dimachkie, M. M., MD (University of Kansas Medical Center, Kansas, City, Doppler, K., Echaniz-Laguna, A., MD (Hopital de Hautepierre, Strasbourgh, France), Eftimov, F., PhD (Amsterdam University Medical Centre, Amsterdam, Fazio, R., MD (Scientific Institute San Raffaele, Fokke, C., MD (Gelre Hospital, Zutphen and Apeldoorn, Fulgenzi, E. A., MD (Hospital Cesar Milstein Buenos Aires, Garssen, M. P. J., PhD (Jeroen Bosch Hospital, Hertogenbosch, ’S, Zaltbommel and Drunen, Gijsbers, C. J., MD (Vlietland Hospital, Schiedam, Gilhuis, J., PhD (Reinier de Graaf Gasthuis, Delft, Grapperon, A., MD (CHU Timone, Hsieh, S. T., Illa, I., Islam, B., PhD (International Centre for Diarrhoeal Disease Research, Bangladesh, (icddr, Dhaka, b), Bangladesh), Jellema, K., PhD (Haaglanden Medisch Centrum, The, Hague, Kaida, K., PhD (National Defense Medical College, Saitama, Japan), Kokubun, N., MD (Dokkyo Medical University, Tochigi, Japan), Kolb, N., MD (University of Vermont, Burlington, Vt, van Koningsveld, R., PhD (Elkerliek Hospital, Helmond and Deurne, van der Kooi, A. J., Kuitwaard, K., PhD (Albert Schweitzer Hospital, Dordrecht, Landschoff Lassen, L., MD (Glostrup Hospital, Glostrup, Denmark), Leonhard, S. E., Mandarakas, M., PhD (Erasmus University Medical Centre, Martinez Hernandez, E., MD (Institut d’Investigacions Biomèdiques August Pi, i Sunyer (IDIBAPS), Hospital, Clinic, Mohammad, Q. D., PhD (National Institute of Neurosciences and Hospital, Dhaka, Bangladesh), Pulley, M., MD (University of Florida, Jacksonville, USA), Rajabally, Y. A., PhD (Queen Elizabeth Hospital, Birmingham, UK), Reddel, S. W., PhD (Concord Repatriation General Hospital, Sydney, Australia), van der Ree, T., (Westfriesgasthuis, Md, Hoorn, Roodbol, J., Sachs, G. M., MD (University of Rhode Island, Providence, USA), Samijn, J. P. A., PhD (Maasstad Hospital, Santoro, L., PhD (University Federico II, Napels, Italy), Stein, B., Joseph’s Regional Medical Center, MD (St., Paterson, USA), Vermeij, F. H., MD (Franciscus Gasthuis, Visser, L. H., PhD (Elisabeth-TweeSteden Hospital, Tilburg and Waalwijk, Willison, H. J., PhD (University of Glasgow, Wirtz, P., Phd, (HagaZiekenhuis, Zivkovich, S. A., PhD (University of Pittsburgh Medical Center, and Pittsburgh, USA).

Subjects
treatment, disability evaluation, drug administration schedule, adult, guillain-barré syndrome, poor prognosis, second ivig course, aged, female, guillain-barre syndrome, humans, immunoglobulin g, immunoglobulins, intravenous, immunologic factors, male, middle aged, prognosis, time factors, treatment outcome
Published
2020

15. A Phase 2, Double-Blind, randomized, Dose-Ranging trial Of Reldesemtiv in patients with ALS

Author

Shefner, J.M., Andrews, J.A., Genge, A., Jackson, C., Lechtzin, N., Miller, T.M., Cockroft, B.M., Meng, L., Wei, J., Wolff, A.A., Malik, F.I., Bodkin, C., Brooks, B.R., Caress, J., Dionne, A., Fee, D., Goutman, S.A., Goyal, N.A., Hardiman, O., Hayat, G., Heiman-Patterson, T., Heitzman, D., Henderson, R.D., Johnston, W., Karam, C., Kiernan, M.C., Kolb, S.J., Korngut, L., Ladha, S., Matte, G., Mora, J.S., Needham, M., Oskarsson, B., Pattee, G.L., Pioro, E.P., Pulley, M., Quan, D., Rezania, K., Schellenberg, K.L., Schultz, D., Shoesmith, C., Simmons, Z., Statland, J., Sultan, S., Swenson, A., Berg, L.H.V.D., Vu, T., Vucic, S., Weiss, M., Whyte-Rayson, A., Wymer, J., Zinman, L., Rudnicki, S.A., Shefner, J.M., Andrews, J.A., Genge, A., Jackson, C., Lechtzin, N., Miller, T.M., Cockroft, B.M., Meng, L., Wei, J., Wolff, A.A., Malik, F.I., Bodkin, C., Brooks, B.R., Caress, J., Dionne, A., Fee, D., Goutman, S.A., Goyal, N.A., Hardiman, O., Hayat, G., Heiman-Patterson, T., Heitzman, D., Henderson, R.D., Johnston, W., Karam, C., Kiernan, M.C., Kolb, S.J., Korngut, L., Ladha, S., Matte, G., Mora, J.S., Needham, M., Oskarsson, B., Pattee, G.L., Pioro, E.P., Pulley, M., Quan, D., Rezania, K., Schellenberg, K.L., Schultz, D., Shoesmith, C., Simmons, Z., Statland, J., Sultan, S., Swenson, A., Berg, L.H.V.D., Vu, T., Vucic, S., Weiss, M., Whyte-Rayson, A., Wymer, J., Zinman, L., and Rudnicki, S.A.

Abstract

To evaluate safety, dose response, and preliminary efficacy of reldesemtiv over 12 weeks in patients with amyotrophic lateral sclerosis (ALS). Methods: Patients (≤2 years since diagnosis) with slow upright vital capacity (SVC) of ≥60% were randomized 1:1:1:1 to reldesemtiv 150, 300, or 450 mg twice daily (bid) or placebo; active treatment was 12 weeks with 4-week follow-up. Primary endpoint was change in percent predicted SVC at 12 weeks; secondary measures included ALS Functional Rating Scale-Revised (ALSFRS-R) and muscle strength mega-score. Results: Patients (N = 458) were enrolled; 85% completed 12-week treatment. The primary analysis failed to reach statistical significance (p = 0.11); secondary endpoints showed no statistically significant effects (ALSFRS-R, p = 0.09; muscle strength mega-score, p = 0.31). Post hoc analyses pooling all active reldesemtiv-treated patients compared against placebo showed trends toward benefit in all endpoints (progression rate for SVC, ALSFRS-R, and muscle strength mega-score (nominal p values of 0.10, 0.01 and 0.20 respectively)). Reldesemtiv was well tolerated, with nausea and fatigue being the most common side effects. A dose-dependent decrease in estimated glomerular filtration rate was noted, and transaminase elevations were seen in approximately 5% of patients. Both hepatic and renal abnormalities trended toward resolution after study drug discontinuation. Conclusions: Although the primary efficacy analysis did not demonstrate statistical significance, there were trends favoring reldesemtiv for all three endpoints, with effect sizes generally regarded as clinically important. Tolerability was good; modest hepatic and renal abnormalities were reversible. The impact of reldesemtiv on patients with ALS should be assessed in a pivotal Phase 3 trial. (ClinicalTrials.gov Identifier: NCT03160898)

Published
2020

16. NEO1/NEO-EXT studies:Safety and exploratory efficacy of repeat avalglucosidase alfa dosing after up to 6 years in late-onset Pompe disease (LOPD)

Author

Schoser, B., Barohn, R., Byrne, B., Goker-Alpan, O., Kishnani, P., Ladha, S., Laforet, P., Mengel, E., Pena, L., Sacconi, S., Straub, V., Trivedi, J., Van Damme, P., van der Ploeg, A., Vissing, J., Young, P., Haack, K., Ivanina, I., Wang, Y., Dimachkie, M., Schoser, B., Barohn, R., Byrne, B., Goker-Alpan, O., Kishnani, P., Ladha, S., Laforet, P., Mengel, E., Pena, L., Sacconi, S., Straub, V., Trivedi, J., Van Damme, P., van der Ploeg, A., Vissing, J., Young, P., Haack, K., Ivanina, I., Wang, Y., and Dimachkie, M.

Published
2020

25. AUTOPHAGIC MYOPATHIES / MYOFIBRILLAR MYOPATHIES / DISTAL MYOPATHIES / POMPE DISEASE

Author

Schoser, B., primary, Barohn, R., additional, Byrne, B., additional, Goker-Alpan, O., additional, Kishnani, P., additional, Ladha, S., additional, Laforet, P., additional, Mengel, E., additional, Pena, L., additional, Sacconi, S., additional, Straub, V., additional, Trivedi, J., additional, Van Damme, P., additional, van der Ploeg, A., additional, Vissing, J., additional, Young, P., additional, Haack, K., additional, Ivanina, I., additional, Wang, Y., additional, and Dimachkie, M., additional

Published
2020
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28. Long-term safety and efficacy of subcutaneous immunoglobulin IgPro20 in CIDP: PATH extension study

Author

van Schaik, Ivo N, Mielke, Orell, Bril, Vera, van Geloven, Nan, Hartung, Hans-Peter, Lewis, Richard A, Sobue, Gen, Lawo, John-Philip, Praus, Michaela, Durn, Billie L, Cornblath, David R, Merkies, Ingemar SJ, Sabet, A, George, K, Roberts, L, Carne, R, Blum, S, Henderson, R, Van Damme, P, Demeestere, J, Larue, S, D'Amour, C, Bril, V, Breiner, A, Kunc, P, Michal, V, Sussova, J, Tomas, K, Talab, R, Michal, B, 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, Zschumtszsch, 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, IN, Eftimov, F, Notermans, NC, 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, Simpson, E, Lai, E Chi-Ho, Dimachkie, M, Barohn, RJ, 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, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Hagenacker, Tim (Beitragende*r), HUS Neurocenter, Neurologian yksikkö, Clinicum, Department of Neurosciences, Academic Medical Center, and CSL Behring

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Injections, Subcutaneous, Medizin, Chronic inflammatory demyelinating polyneuropathy, Subcutaneous immunoglobulin, INFLAMMATORY DEMYELINATING POLYNEUROPATHY, Gastroenterology, 3124 Neurology and psychiatry, law.invention, 03 medical and health sciences, MUSCLE STRENGTH, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Humans, Medicine, Prospective Studies, Dosing, Adverse effect, Prospective cohort study, Aged, 030304 developmental biology, 0303 health sciences, MMN, business.industry, Extension study, 3112 Neurosciences, Immunoglobulins, Intravenous, Polyradiculoneuropathy, Middle Aged, medicine.disease, 3. Good health, Treatment Outcome, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, Neurology, Immunoglobulin G, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

PATH study group., [Objective] To investigate the long-term safety and efficacy of weekly subcutaneous IgPro20 (Hizentra, CSL Behring) in chronic inflammatory demyelinating polyneuropathy (CIDP)., [Methods] In a 48-week open-label prospective extension study to the PATH study, patients were initially started on 0.2 g/kg or on 0.4 g/kg weekly and—if clinically stable—switched to 0.2 g/kg weekly after 24 weeks. Upon CIDP relapse on the 0.2 g/kg dose, 0.4 g/kg was (re)initiated. CIDP relapse was defined as a deterioration by at least 1 point in the total adjusted Inflammatory Neuropathy Cause and Treatment score., [Results] Eighty-two patients were enrolled. Sixty-two patients initially received 0.4 g/kg, 20 patients 0.2 g/kg weekly. Seventy-two received both doses during the study. Sixty-six patients (81%) completed the 48-week study duration. Overall relapse rates were 10% in 0.4 g/kg–treated patients and 48% in 0.2 g/kg–treated patients. After dose reduction from 0.4 to 0.2 g/kg, 51% (27/53) of patients relapsed, of whom 92% (24 of 26) improved after reinitiation of the 0.4 g/kg dose. Two-thirds of patients (19/28) who completed the PATH study without relapse remained relapse-free on the 0.2 g/kg dose after dose reduction in the extension study. Sixty-two patients had adverse events (AEs) (76%), of which most were mild or moderate with no related serious AEs., [Conclusions] Subcutaneous treatment with IgPro20 provided long-term benefit at both 0.4 and 0.2 g/kg weekly doses with lower relapse rates on the higher dose. Long-term dosing should be individualized to find the most appropriate dose in a given patient. Classification of evidence This study provides Class IV evidence that for patients with CIDP, long-term treatment with SCIG beyond 24 weeks is safe and efficacious., This study was supported by CSL Behring.

Published
2019

31. Restabilization treatment after intravenous immunoglobulin withdrawal in chronic inflammatory demyelinating polyneuropathy: Results from the pre-randomization phase of the Polyneuropathy And Treatment with Hizentra study

Author

Mielke, Orell, Bril, Vera, Cornblath, David R., Lawo, John-Philip, van Geloven, Nan, Hartung, Hans-Peter, Lewis, Richard A., Merkies, Ingemar S. J., Sobue, Gen, Durn, Billie, Shebl, Amgad, van Schaik, Ivo N., 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., Simpson, E., 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., Mielke, Orell, Bril, Vera, Cornblath, David R., Lawo, John-Philip, van Geloven, Nan, Hartung, Hans-Peter, Lewis, Richard A., Merkies, Ingemar S. J., Sobue, Gen, Durn, Billie, Shebl, Amgad, van Schaik, Ivo N., 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., Simpson, E., 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., and Gable, K.

Abstract

In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), intravenous immunoglobulin (IVIG) is recommended to be periodically reduced to assess the need for ongoing therapy. However, little is known about the effectiveness of restabilization with IVIG in patients who worsen after IVIG withdrawal. In the Polyneuropathy And Treatment with Hizentra (PATH) study, the pre-randomization period included sudden stopping of IVIG followed by 12 weeks of observation. Those deteriorating were then restabilized with IVIG. Of 245 subjects who stopped IVIG, 28 did not show signs of clinical deterioration within 12 weeks. Two hundred and seven received IVIG restabilization with an induction dose of 2 g/kg bodyweight (bw) IgPro10 (Privigen, CSL Behring, King of Prussia, Pennsylvania) and maintenance doses of 1 g/kg bw every 3 weeks for up to 13 weeks. Signs of clinical improvement were seen in almost all (n = 188; 91%) subjects. During IVIG restabilization, 35 subjects either did not show CIDP stability (n = 21, analyzed as n = 22 as an additional subject was randomized in error) or withdrew for other reasons (n = 14). Of the 22 subjects who did not achieve clinical stability, follow-up information in 16 subjects after an additional 4 weeks was obtained. Nine subjects were reported to have improved, leaving a maximum of 27 subjects (13%) who either showed no signs of clinical improvement during the restabilization phase and 4 weeks post-study or withdrew for other reasons. In conclusion, sudden IVIG withdrawal was effective in detecting ongoing immunoglobulin G dependency with a small risk for subjects not returning to their baseline 17 weeks after withdrawal.

Published
2019

32. Long-term safety and efficacy of subcutaneous immunoglobulin IgPro20 in CIDP PATH extension study

Author

van Schaik, Ivo N., Mielke, Orell, Bril, Vera, van Geloven, Nan, Hartung, Hans-Peter, Lewis, Richard A., Sobue, Gen, Lawo, John-Philip, Praus, Michaela, Durn, Billie L., Cornblath, David R., Merkies, Ingemar S. J., Sabet, A., George, K., Roberts, L., Carne, R., Blum, S., Henderson, R., Van Damme, P., Demeestere, J., Larue, S., D'Amour, C., Bril, V, Breiner, A., Kunc, P., Michal, V, Sussova, J., Tomas, K., Talab, R., Michal, B., 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., Zschumtszsch, 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., Simpson, E., 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., van Schaik, Ivo N., Mielke, Orell, Bril, Vera, van Geloven, Nan, Hartung, Hans-Peter, Lewis, Richard A., Sobue, Gen, Lawo, John-Philip, Praus, Michaela, Durn, Billie L., Cornblath, David R., Merkies, Ingemar S. J., Sabet, A., George, K., Roberts, L., Carne, R., Blum, S., Henderson, R., Van Damme, P., Demeestere, J., Larue, S., D'Amour, C., Bril, V, Breiner, A., Kunc, P., Michal, V, Sussova, J., Tomas, K., Talab, R., Michal, B., 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., Zschumtszsch, 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., Simpson, E., 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., and Gable, K.

Abstract

Objective To investigate the long-term safety and efficacy of weekly subcutaneous IgPro20 (Hizentra, CSL Behring) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods In a 48-week open-label prospective extension study to the PATH study, patients were initially started on 0.2 g/kg or on 0.4 g/kg weekly and-if clinically stable-switched to 0.2 g/kg weekly after 24 weeks. Upon CIDP relapse on the 0.2 g/kg dose, 0.4 g/kg was (re)initiated. CIDP relapse was defined as a deterioration by at least 1 point in the total adjusted Inflammatory Neuropathy Cause and Treatment score. Results Eighty-two patients were enrolled. Sixty-two patients initially received 0.4 g/kg, 20 patients 0.2 g/kg weekly. Seventy-two received both doses during the study. Sixty-six patients (81%) completed the 48-week study duration. Overall relapse rates were 10% in 0.4 g/kg-treated patients and 48% in 0.2 g/kg-treated patients. After dose reduction from 0.4 to 0.2 g/kg, 51% (27/53) of patients relapsed, of whom 92% (24 of 26) improved after reinitiation of the 0.4 g/kg dose. Two-thirds of patients (19/28) who completed the PATH study without relapse remained relapse-free on the 0.2 g/kg dose after dose reduction in the extension study. Sixty-two patients had adverse events (AEs) (76%), of which most were mild or moderate with no related serious AEs. Conclusions Subcutaneous treatment with IgPro20 provided long-term benefit at both 0.4 and 0.2 g/kg weekly doses with lower relapse rates on the higher dose. Long-term dosing should be individualized to find the most appropriate dose in a given patient. Classification of evidence This study provides Class IV evidence that for patients with CIDP, long-term treatment with SCIG beyond 24 weeks is safe and efficacious.

Published
2019

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

Author

Merkies, ISJ, van Schaik, IN, Leger, J-M, Bril, V, van Geloven, N, Hartung, H-P, Lewis, RA, Sobue, G, Lawo, J-P, Durn, BL, Cornblath, DR, De Bleecker, JL, Sommer, C, Robberecht, W, Saarela, M, Kamienowski, J, Stelmasiak, Z, Tackenberg, B, Mielke, O, 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, Auranen, M, Pouget, J, Attarian, S, Le Masson, G, Wielanek-Bachelet, A, Desnuelle, C, Delmont, E, Clavelou, P, Aufauvre, D, Schmidt, J, Zschuentzsch, J, 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, Eftimov, F, Notermans, NC, 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, Simpson, Lai, EC-H, Dimachkie, M, Barohn, RJ, 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, Franques, J, Morales, RJ, Nguento, A, Schrey, C, Zwolinska, G, Merkies, ISJ, van Schaik, IN, Leger, J-M, Bril, V, van Geloven, N, Hartung, H-P, Lewis, RA, Sobue, G, Lawo, J-P, Durn, BL, Cornblath, DR, De Bleecker, JL, Sommer, C, Robberecht, W, Saarela, M, Kamienowski, J, Stelmasiak, Z, Tackenberg, B, Mielke, O, 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, Auranen, M, Pouget, J, Attarian, S, Le Masson, G, Wielanek-Bachelet, A, Desnuelle, C, Delmont, E, Clavelou, P, Aufauvre, D, Schmidt, J, Zschuentzsch, J, 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, Eftimov, F, Notermans, NC, 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, Simpson, Lai, EC-H, Dimachkie, M, Barohn, RJ, 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, Franques, J, Morales, RJ, Nguento, A, Schrey, C, 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)-naïve 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

34. Restabilization treatment after intravenous immunoglobulin withdrawal in chronic inflammatory demyelinating polyneuropathy: Results from the pre-randomization phase of the Polyneuropathy And Treatment with Hizentra study

Author

Mielke, O, Bril, V, Cornblath, DR, Lawo, J-P, van Geloven, N, Hartung, H-P, Lewis, RA, Merkies, ISJ, Sobue, G, Durn, B, Shebl, A, van Schaik, IN, 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, Eftimov, F, Notermans, NC, 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, Simpson, E, Lai, EC-H, Dimachkie, M, Barohn, RJ, 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, Mielke, O, Bril, V, Cornblath, DR, Lawo, J-P, van Geloven, N, Hartung, H-P, Lewis, RA, Merkies, ISJ, Sobue, G, Durn, B, Shebl, A, van Schaik, IN, 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, Eftimov, F, Notermans, NC, 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, Simpson, E, Lai, EC-H, Dimachkie, M, Barohn, RJ, 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, and Gable, K

Abstract

In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), intravenous immunoglobulin (IVIG) is recommended to be periodically reduced to assess the need for ongoing therapy. However, little is known about the effectiveness of restabilization with IVIG in patients who worsen after IVIG withdrawal. In the Polyneuropathy And Treatment with Hizentra (PATH) study, the pre-randomization period included sudden stopping of IVIG followed by 12 weeks of observation. Those deteriorating were then restabilized with IVIG. Of 245 subjects who stopped IVIG, 28 did not show signs of clinical deterioration within 12 weeks. Two hundred and seven received IVIG restabilization with an induction dose of 2 g/kg bodyweight (bw) IgPro10 (Privigen, CSL Behring, King of Prussia, Pennsylvania) and maintenance doses of 1 g/kg bw every 3 weeks for up to 13 weeks. Signs of clinical improvement were seen in almost all (n = 188; 91%) subjects. During IVIG restabilization, 35 subjects either did not show CIDP stability (n = 21, analyzed as n = 22 as an additional subject was randomized in error) or withdrew for other reasons (n = 14). Of the 22 subjects who did not achieve clinical stability, follow-up information in 16 subjects after an additional 4 weeks was obtained. Nine subjects were reported to have improved, leaving a maximum of 27 subjects (13%) who either showed no signs of clinical improvement during the restabilization phase and 4 weeks post-study or withdrew for other reasons. In conclusion, sudden IVIG withdrawal was effective in detecting ongoing immunoglobulin G dependency with a small risk for subjects not returning to their baseline 17 weeks after withdrawal.

Published
2019

35. P.69NEO1 and NEO-EXT studies: exploratory efficacy of repeat avalglucosidase alfa dosing for up to 5 years in participants with late-onset Pompe disease (LOPD)

Author

Schoser, B., primary, Barohn, R., additional, Byrne, B., additional, Goker-Alpan, O., additional, Kishnani, P., additional, Ladha, S., additional, Laforêt, P., additional, Mengel, K., additional, Pena, L., additional, Sacconi, S., additional, Straub, V., additional, Trivedi, J., additional, Van Damme, P., additional, van der Ploeg, A., additional, Vissing, J., additional, Young, P., additional, An Haack, K., additional, Liu, K., additional, Fraser, P., additional, and Dimachkie, M., additional

Published
2019
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36. Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

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

Published
2018
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37. Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis

Author

Gendron, T.F. (Tania F.), Chew, J. (Jeannie), Stankowski, J.N. (Jeannette N.), Hayes, L.R. (Lindsey R.), Zhang, Y.-J. (Yong-Jie), Prudencio, M. (Mercedes), Carlomagno, Y. (Yari), Daughrity, L.M. (Lillian M.), Jansen-West, K. (Karen), Perkerson, E.A. (Emilie A.), O'Raw, A. (Aliesha), Cook, C. (Casey), Pregent, L. (Luc), Belzil, V. (Veronique), Van Blitterswijk, M. (Marka), Tabassian, L.J. (Lilia J.), Lee, C.W. (Chris W.), Yue, M. (Mei), Tong, J. (Jimei), Song, Y. (Yuping), Castanedes-Casey, M. (Monica), Rousseau, L. (Linda), Phillips, V. (Virginia), Dickson, D. (Dennis), Rademakers, S. (Suzanne), Fryer, J.D. (John D.), Rush, B.K. (Beth K.), Pedraza, O. (Otto), Caputo, A.M. (Ana M.), Desaro, P. (Pamela), Palmucci, C. (Carla), Robertson, A. (Amelia), Heckman, M.G. (Michael G.), Diehl, N.N. (Nancy N.), Wiggs, E. (Edythe), Tierney, M. (Michael), Braun, L. (Laura), Farren, J. (Jennifer), Lacomis, D. (David), Ladha, S. (Shafeeq), Fournier, C.N. (Christina N.), McCluskey, L. (Leo), Elman, L. (Lauren), Toledo, J.B. (Jon B.), McBride, J.D. (Jennifer D.), Tiloca, C. (Cinzia), Morelli, C. (Claudia), Poletti, B. (Barbara), Solca, F. (Federica), Prelle, A. (Alessandro), Wuu, J. (Joanne), Jockel-Balsarotti, J. (Jennifer), Rigo, F. (Frank), Ambrose, C. (Christine), Datta, A. (Abhishek), Yang, W. (Weixing), Raitcheva, D. (Denitza), Antognetti, G. (Giovanna), McCampbell, A. (Alexander), Swieten, J.C. (John) van, Miller, B.L. (Bruce Lars), Boxer, A.L. (Adam), Brown, R.H. (Robert H.), Bowser, R. (Robert), Miller, T.M. (Timothy M.), Trojanowski, J.Q. (John), Grossman, M. (Murray), Berry, J.D. (James D.), Hu, W.T. (William), Ratti, A. (Antonia), Traynor, B. (Bryan), Disney, M. (Matthew), Benatar, M. (Michael), Silani, V. (Vincenzo), Glass, J.D. (Jonathan D.), Floeter, M.K. (Mary Kay), Rothstein, J. (Jeffrey), Boylan, K.B. (Kevin B.), Petrucelli, L. (Leonard), Gendron, T.F. (Tania F.), Chew, J. (Jeannie), Stankowski, J.N. (Jeannette N.), Hayes, L.R. (Lindsey R.), Zhang, Y.-J. (Yong-Jie), Prudencio, M. (Mercedes), Carlomagno, Y. (Yari), Daughrity, L.M. (Lillian M.), Jansen-West, K. (Karen), Perkerson, E.A. (Emilie A.), O'Raw, A. (Aliesha), Cook, C. (Casey), Pregent, L. (Luc), Belzil, V. (Veronique), Van Blitterswijk, M. (Marka), Tabassian, L.J. (Lilia J.), Lee, C.W. (Chris W.), Yue, M. (Mei), Tong, J. (Jimei), Song, Y. (Yuping), Castanedes-Casey, M. (Monica), Rousseau, L. (Linda), Phillips, V. (Virginia), Dickson, D. (Dennis), Rademakers, S. (Suzanne), Fryer, J.D. (John D.), Rush, B.K. (Beth K.), Pedraza, O. (Otto), Caputo, A.M. (Ana M.), Desaro, P. (Pamela), Palmucci, C. (Carla), Robertson, A. (Amelia), Heckman, M.G. (Michael G.), Diehl, N.N. (Nancy N.), Wiggs, E. (Edythe), Tierney, M. (Michael), Braun, L. (Laura), Farren, J. (Jennifer), Lacomis, D. (David), Ladha, S. (Shafeeq), Fournier, C.N. (Christina N.), McCluskey, L. (Leo), Elman, L. (Lauren), Toledo, J.B. (Jon B.), McBride, J.D. (Jennifer D.), Tiloca, C. (Cinzia), Morelli, C. (Claudia), Poletti, B. (Barbara), Solca, F. (Federica), Prelle, A. (Alessandro), Wuu, J. (Joanne), Jockel-Balsarotti, J. (Jennifer), Rigo, F. (Frank), Ambrose, C. (Christine), Datta, A. (Abhishek), Yang, W. (Weixing), Raitcheva, D. (Denitza), Antognetti, G. (Giovanna), McCampbell, A. (Alexander), Swieten, J.C. (John) van, Miller, B.L. (Bruce Lars), Boxer, A.L. (Adam), Brown, R.H. (Robert H.), Bowser, R. (Robert), Miller, T.M. (Timothy M.), Trojanowski, J.Q. (John), Grossman, M. (Murray), Berry, J.D. (James D.), Hu, W.T. (William), Ratti, A. (Antonia), Traynor, B. (Bryan), Disney, M. (Matthew), Benatar, M. (Michael), Silani, V. (Vincenzo), Glass, J.D. (Jonathan D.), Floeter, M.K. (Mary Kay), Rothstein, J. (Jeffrey), Boylan, K.B. (Kevin B.), and Petrucelli, L. (Leonard)

Abstract

There is no effective treatment for amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease. However, discovery of a G4C2 repeat expansion in the C9ORF72 gene as the most common genetic cause of ALS has opened up new avenues for therapeutic intervention for this form of ALS. G4C2 repeat expansion RNAs and proteins of repeating dipeptides synthesized from these transcripts are believed to play a key role in C9ORF72-associated ALS (c9ALS). Therapeutics that target G4C2 RNA, such as antisense oligonucleotides (ASOs) and small molecules, are thus being actively investigated. A limitation in moving such treatments from bench to bedside is a lack of pharmacodynamic markers for use in clinical trials. We explored whether poly(GP) proteins translated from G4C2 RNA could serve such a purpose. Poly(GP) proteins were detected in cerebrospinal fluid (CSF) and in peripheral blood mononuclear cells from c9ALS patients and, notably, from asymptomatic C9ORF72 mutation carriers. Moreover, CSF poly(GP) proteins remained relatively constant over time, boding well for their use in gauging biochemical responses to potential treatments. Treating c9ALS patient cells or a mouse model of c9ALS with ASOs that target G4C2 RNA resulted in decreased intracellular and extracellular poly(GP) proteins. This decrease paralleled reductions in G4C2 RNA and downstream G4C2 RNA-mediated events. These findings indicate that tracking poly(GP) proteins in CSF could provide a means to assess target engagement of G4C2 RNA-based therapies in symptomatic C9ORF72 repeat expansion carriers and presymptomatic individuals who are expected to benefit from early therapeutic intervention. 2017

Published
2017
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38. International Guillain-Barré Syndrome Outcome Study: protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Author

Jacobs, B, van den Berg, B, Verboon, C, Chavada, G, Cornblath, D, Gorson, K, Harbo, T, Hartung, H, Hughes, R, Kusunoki, S, van Doorn, P, Willison, H, van Woerkom, M, Roodbol, J, Reisin, R, Reddel, S, Islam, Z, Islam, B, Mohammad, Q, van den Bergh, P, Feasby, T, Wang, Y, Pã©rã©on, Y, Lehmann, H, Dardiotis, E, Nobile Orazio, E, Shahrizaila, N, Bateman, K, Illa, I, Querol, L, Hsieh, S, Davidson, A, Addington, J, Ajroud Driss, S, Andersen, H, Antonini, G, Attarian, S, Badrising, U, Barroso, F, Benedetti, L, Beronio, A, Bianco, M, Binda, D, Briani, C, Bã1⁄4rmann, J, Bella, I, Bertorini, T, Bhavaraju Sanka, R, Brannagan, T, Busby, M, Butterworth, S, Campagnolo, M, Casasnovas, C, Cavaletti, G, Chao, C, Chen, S, Chetty, S, Claeys, K, Cohen, J, Conti, M, Cosgrove, J, Dalakas, M, Dimachkie, M, Dillmann, U, Domínguez González, C, Doppler, K, Dornonville de la Cour, C, Echaniz Laguna, A, Eftimov, F, Faber, C, Fazio, R, Fokke, C, Fujioka, T, Fulgenzi, E, Galassi, G, Garcia, T, Garnero, M, Garssen, M, Gijsbers, C, Gilchrist, J, Gilhuis, H, Goldstein, J, Goyal, N, Granit, V, Grapperon, A, Gutiérrez Gutiérrez, G, Gutmann, L, Hadden, R, Holbech, J, Holt, J, Homedes Pedret, C, Htut, M, Jellema, K, JericÃ3 Pascual, I, Kaida, K, Karafiath, S, Katzberg, H, Kiers, L, Kieseier, B, Kimpinski, K, Kleyweg, R, Kokubun, N, Kolb, N, Kuitwaard, K, Kuwabara, S, Kwan, J, Ladha, S, Landschoff Lassen, L, Lawson, V, Ledingham, D, Léon Cejas, L, Luciano, C, Lucy, S, Lunn, M, Magot, A, Manji, H, Marchesoni, C, Marfia, G, Márquez Infante, C, Martinez Hernandez, E, Mataluni, G, Mattiazi, M, Mcdermott, C, Meekins, G, Miller, J, Monges, M, Montero, M, Morís de la Tassa, G, Nascimbene, C, Neumann, C, Nowak, R, Orizaola Balaguer, P, Osei Bonsu, M, Pan, E, Pardo Fernandez, J, Pasnoor, M, Pulley, M, Rajabally, Y, Rinaldi, S, Ritter, C, Roberts, R, Rojas Marcos, I, Rudnicki, S, Sachs, G, Samijn, J, Santoro, L, Saperstein, D, Savransky, A, Schneider, H, Schenone, A, Sedano Tous, M, Sekiguchi, Y, Sheikh, K, Silvestri, N, Sindrup, S, Sommer, C, Stein, B, Stino, A, Spyropoulos, A, Srinivasan, J, Suzuki, H, Taylor, S, Tankisi, H, Tigner, D, Twydell, P, Valzania, F, van Damme, P, van der Kooi, A, van Dijk, G, van der Ree, T, van Koningsveld, R, Varrato, J, Vermeij, F, Verschuuren, J, Visser, L, Vytopil, M, Waheed, W, Wilken, M, Wilkerson, C, Wirtz, P, Yamagishi, Y, Yiu, E, Zhou, L, Zivkovic, S, Zivkovic, S., BINDA, DAVIDE, CAVALETTI, GUIDO ANGELO, Jacobs, B, van den Berg, B, Verboon, C, Chavada, G, Cornblath, D, Gorson, K, Harbo, T, Hartung, H, Hughes, R, Kusunoki, S, van Doorn, P, Willison, H, van Woerkom, M, Roodbol, J, Reisin, R, Reddel, S, Islam, Z, Islam, B, Mohammad, Q, van den Bergh, P, Feasby, T, Wang, Y, Pã©rã©on, Y, Lehmann, H, Dardiotis, E, Nobile Orazio, E, Shahrizaila, N, Bateman, K, Illa, I, Querol, L, Hsieh, S, Davidson, A, Addington, J, Ajroud Driss, S, Andersen, H, Antonini, G, Attarian, S, Badrising, U, Barroso, F, Benedetti, L, Beronio, A, Bianco, M, Binda, D, Briani, C, Bã1⁄4rmann, J, Bella, I, Bertorini, T, Bhavaraju Sanka, R, Brannagan, T, Busby, M, Butterworth, S, Campagnolo, M, Casasnovas, C, Cavaletti, G, Chao, C, Chen, S, Chetty, S, Claeys, K, Cohen, J, Conti, M, Cosgrove, J, Dalakas, M, Dimachkie, M, Dillmann, U, Domínguez González, C, Doppler, K, Dornonville de la Cour, C, Echaniz Laguna, A, Eftimov, F, Faber, C, Fazio, R, Fokke, C, Fujioka, T, Fulgenzi, E, Galassi, G, Garcia, T, Garnero, M, Garssen, M, Gijsbers, C, Gilchrist, J, Gilhuis, H, Goldstein, J, Goyal, N, Granit, V, Grapperon, A, Gutiérrez Gutiérrez, G, Gutmann, L, Hadden, R, Holbech, J, Holt, J, Homedes Pedret, C, Htut, M, Jellema, K, JericÃ3 Pascual, I, Kaida, K, Karafiath, S, Katzberg, H, Kiers, L, Kieseier, B, Kimpinski, K, Kleyweg, R, Kokubun, N, Kolb, N, Kuitwaard, K, Kuwabara, S, Kwan, J, Ladha, S, Landschoff Lassen, L, Lawson, V, Ledingham, D, Léon Cejas, L, Luciano, C, Lucy, S, Lunn, M, Magot, A, Manji, H, Marchesoni, C, Marfia, G, Márquez Infante, C, Martinez Hernandez, E, Mataluni, G, Mattiazi, M, Mcdermott, C, Meekins, G, Miller, J, Monges, M, Montero, M, Morís de la Tassa, G, Nascimbene, C, Neumann, C, Nowak, R, Orizaola Balaguer, P, Osei Bonsu, M, Pan, E, Pardo Fernandez, J, Pasnoor, M, Pulley, M, Rajabally, Y, Rinaldi, S, Ritter, C, Roberts, R, Rojas Marcos, I, Rudnicki, S, Sachs, G, Samijn, J, Santoro, L, Saperstein, D, Savransky, A, Schneider, H, Schenone, A, Sedano Tous, M, Sekiguchi, Y, Sheikh, K, Silvestri, N, Sindrup, S, Sommer, C, Stein, B, Stino, A, Spyropoulos, A, Srinivasan, J, Suzuki, H, Taylor, S, Tankisi, H, Tigner, D, Twydell, P, Valzania, F, van Damme, P, van der Kooi, A, van Dijk, G, van der Ree, T, van Koningsveld, R, Varrato, J, Vermeij, F, Verschuuren, J, Visser, L, Vytopil, M, Waheed, W, Wilken, M, Wilkerson, C, Wirtz, P, Yamagishi, Y, Yiu, E, Zhou, L, Zivkovic, S, Zivkovic, S., BINDA, DAVIDE, and CAVALETTI, GUIDO ANGELO

Abstract

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within 2 weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course, and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1,000 patients with a follow-up of 1–3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1,400 participants from 143 active centers in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modeling, treatment effects, and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS.

Published
2017

44. Technology Valuation Solutions

Author

Ladha, S. and Deevi, S.C.

Subjects
Technology Valuation Solutions (Book) -- Boer, F. Peter, Books -- Book reviews, Business, general, Business, Engineering and manufacturing industries
Abstract

Technology Valuation Solutions; F. Peter Boer; Wiley Publishers, New York, NE; 2004; 204 pp., $89.95. While no company can sustain its leadership position in an industry without continuously inventing new [...]

Published
2005

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