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1. Clinical utility of adjunctive retigabine in partial onset seizures in adults

Author

Rejdak K, Luszczki JJ, Błaszczyk B, Chwedorowicz R, and Czuczwar SJ

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Konrad Rejdak1, Jarogniew J Luszczki2,3, Barbara Blaszczyk4, Roman Chwedorowicz5, Stanislaw J Czuczwar2,51Department of Neurology, Medical University of Lublin, Lublin, 2Department of Pathophysiology, Medical University of Lublin, Lublin, 3Isobolography Analysis Laboratory, Institute of Agricultural Medicine, Lublin, 4Faculty of Health Sciences, High School of Economics and Law, Kielce, 5Department of Physiopathology, Institute of Agricultural Medicine, Lublin, PolandAbstract: In ~30% of epileptic patients, full seizure control is not possible, which is why the search for novel antiepileptic drugs continues. Retigabine exhibits a mechanism of action that is not shared by the available antiepileptic drugs. This antiepileptic enhances potassium currents via Kv7.2–7.3 channels, which very likely results from destabilization of a closed conformation or stabilization of the open conformation of the channels. Generally, the pharmacokinetics of retigabine are linear and the drug undergoes glucuronidation and acetylation. Results from clinical trials indicate that, in the form of an add-on therapy, retigabine proves an effective drug in refractory epileptic patients. The major adverse effects of the add-on treatment are dizziness, somnolence, and fatigue. This epileptic drug is also considered for other conditions – neuropathic pain, affective disorders, stroke, or even Alzheimer’s disease.Keywords: antiepileptic drugs, epilepsy, seizure control

Published
2012

2. Effect of the Factor XIa Inhibitor Asundexian According to Baseline Infarct Pattern and on MRI Covert Infarct Outcomes

Author

Smith, Eric E., Shoamanesh, Ashkan, Xu, Lizhen, Heenan, Laura, Saad, Feryal, Colorado, Pablo, Chen, Chih-Hao, Lemmens, Robin, De Marchis, Gian Marco, Caso, Valeria, Masjuan, Jaime, Hirano, Teruyuki, Milanov, Ivan, Campbell, Bruce C.V., Mas, Jean-Louis, Connolly, Stuart J., Mundl, Hardi, Hart, Robert G., Bailey, P., Kleinig, T., Cordato, D., Choi, P., Garcia-Esperon, C., Chew, A., Cloud, G., Stanislaus, V., Krause, M., Priglinger, M., Grimley, R., Ghia, D., Sahathevan, R., Brown, H., Kwan, C., Devlin, M., Greisenegger, S., Bonelli-Nauer, S., Rath, J., Langer, A., Marko, M., Ferrari, J., Bernegger, A., Baumgartinger, M., Vigl, M., Krebs, S., Lang, W., Knoflach, M., Dejakum, B., Kiechl, S., Töll, T., Domig, L., Mutzenbach, J.S., Ganser, B., Hecker, C., Rösler, C., Bubel, N., Pikija, S., Zellner, T., Leitner, U., Berger, O., Surböck, B., Beirer, S., Staykov, D., Schrammel, D., Halilovic, A., Frattner, M., Barmherzigen, D., Lampl, C., Höfer, C., Nagl, S., Bocksrucker, C., Demeestere, J., Desfontaines, P., Ciobanu, C., De Pauw, A., Terwecoren, A., Hasenbroekx, M.C., Clement, F., De Klippel, N., Soors, P., Hermans, S., De Raedt, S., Vandervorst, F., Seynaeve, L., Fockaert, N., Smet, S., Rutgers, M., Del Gaudio, N., Paindeville, P., Staikov, I., Simeonova, A., Stoyanova, I., Cholakova, M., Mihnev, N., Petrova, T., Koralova, A., Dimov, D., Kuzev, Y., Danovska, M., Marinova, D., Marinova-Trifonova, D., Ovcharova, E., Mladenovski, I., Yanakieva, M., Stoev, P., Dimitrova, M., Todorova-Georgieva, S., Haralanov, L., Milkov, B., Solakov, D., Petkova, N., Ignatova-Valkova, V., Karabinov, V., Marinova, V., Miteva, Y., Andonova, V., Kasabova, D., Kostadinova, E., Shopova-Vrabcheva, Y., Gatev, D., Semova, D., Halil, E., Kaprelyan, A., Ivanov, B., Panov, G., Grudkova, M., Syuleyman, N., Kalpachki, R., Alexiev, F., Ivanova, I., Kancheva, K., Sakelarova, T., Maslarov, D., Drenska, D., Georgiev, V., Petrova, K., Petrova, N., Ivanova, I., Semerdjieva, N., Zhelyazkov, P., Spasova-Markova, S., Dong, X., Wang, D., Wang, S., Huang, W., Zhao, H., Wang, C., Jie, L., Xinyang, Y., Ping, Z., Dong, Q., Wang, Y., Fuling, Y., Yue, W., Liu, R., Yang, Y., Stetkarova, I., Mikulenka, P., Vasko, P., Peisker, T., Bar, M., Roubec, M., Mikulik, R., Cabukova, M., Vinklarek, J., Kovar, M., Pansky, M., Mencl, P., Skoda, O., Carek, M., Pernicka, M., Skodova, M., Geier, P., Cepkova, J., Drlik, J., Prax, T., Herzig, R., Krajickova, D., Vitkova, E., Haluskova, S., Vaclavik, D., Martinkova, J., Blejcharova, K., Tkacova, M., Pavlik, O., Nevšímalová, M., Rosol, J., Nevsimalova, M., Hruby, R., Iversen, H., Andersen, A.V., Rahimi, D., Christensen, H., Grundtvig, J., Hjort, N., Andersen, G., Sandal, B., Stilund, M., Modrau, B., Strade, A., Porobic, M., Andersen, S.D., Kruuse, C., Ölmestig, J., Kolmos, M., Parvez, A., Christensen, T., Stokholm, J., Jensen, H.B., Putaala, J., Strbian, D., Sibolt, G., Tiainen, M., Martinez-Majander, N., Curtze, S., Raty, S., Kraemer, Y., Roine, R., Aivo, J., Ruuskanen, J., Ylikotila, P., Roine, S., Hallikainen, M., Jakala, P., Kurl, S., Julkunen, V., Sibon, I., Olindo, S., Richard, S., Larrue, V., Gollion, C., Catala, H., Henon, H., Lucie, D.S., Nelly, D., Calvet, D., Malbranque, A., Mazé, B., Barbieux-Ghitu, C., Rosso, C., Samson, Y., Vannier, S., Moulin, T., Bonnet, L., Reiner, P., Buffon, F., Denier, C., Amri, K., Legris, N., Chassin, O., Selli, N., Mariana, S., Berrouschot, J., Stoll, A., Klunk, D., Keilitz, J., Neustadt, M., Zerrenner, S., Veltkamp, R., Hajjar, K., Heeger, A., Winezki, E., Apel, L., Pompsch, M., Mueller, P., Rappard, P., Auer, R., Ringleb, P.A., Berberich, A., Heyse, M., Mundiyanapurath, S., Reiff, T., Poli, S., Gomez-Exposito, A., Mengel, A., Tünnerhoff, J., Adeyemi, K., Poli, K., Kusch, V., Pelz, J., Michalski, D., Wartenberg, K., Althaus, K., Tavares, F., Mueller, S., Soda, H., Rascher, A., Hiermann, E., Weinhardt, R., Weissenborn, K., Leotescu, A., Grosse, G., Worthmann, H., Ernst, J., Gabriel, M., Schuppner, R., Schäfer, J.H., Charisse, D., Gruber, K., Kurka, N., Reitz, S.C., Pfeilschifter, W., Lee, J.I., Gliem, M., Moll, M., Steiner, T., Segura, L., Szegedi, N., Barandi, D., Uhrinakova, L., Czencz, M., Pasztor, M., Gyuker, N., Bartha, N.E., May, Z., Simony, Z., Szasz, G., Kakuk, I., Pető, N., Panczel, G.F., Olah, A., Racz, O., Balla, T., Horvath, B., Tuba, K., Czinderi, V., Klivenyi, P., Annus, A., Hertelendy, P., Szapary, L., Bosnyak, E., Kalmar, P., Karadi, Z., Cziba, L., Olah, L., Berki, A., Hudak, L., Kozák, M., Babel, S., Nemeth, L., Molnár, B., Simon, Z., Roveri, L., Cerri, F., Giacalone, G., Zini, A., Mauro, G., Asioli, G.M., Forlivesi, S., Arnone, G., Fiaccadori, A., Maria Fontana Francesca, E., Allegra, G., Mosconi, M.G., Longoni, M., Terlizzi, R., Paolucci, M., Tassi, R., Franci, B., Lucani, B., Domenichelli, C., Paoletti, D., Acampa, M., Zedde, M.L., Pezzella, F.R., Mangiardi, M., Galizia, P., Anticoli, S., Scalise, S., Lattanzi, S., Norata, D., Cannuccia, M., Cavallini, A., Federica, F., Denaro, M.F., Tosi, P., Sonoda, K., Kawajiri, M., Kusano, Y., Haraguchi, K., Kawano, H., Terasaki, T., Kaneko, C., Murase, S., Kumagai, M., Murai, N., Miyazaki, Y., Mori, T., Hatano, T., Kawanishi, M., Ochiai, J., Ishihara, S., Uehara, T., Yasaka, M., Nakagawa, H., Makino, M., Yonehara, T., Fukushima, Y., Hirotsune, N., Sakai, N., Yamasaki, M., Coutinho, J., Wouters, A., den Hertog, H., Zwartbol, R., Beumer, D., Kerklaan, J., Hilkens, P., Schreuder, T., Propper, D., Slowik, A., Wlodarczyk, E., Wrona, P., Pulyk, R., Lasek-Bal, A., Kosarz-Lanczek, K., Puz, P., Bilik, M., Magielska, A., Zamiela – Żółciak, A., Ochocinska, L., Bahdasaryan, S., Stępień, A., Dębiec, A., Joanna, K., Pawel, M., Jacek, S., Daniel, P., Marta, S., Rejdak, K., Wojczal, J., Luchowski, P., Fryze, W., Wisniewska, A., Krzyzanowska, M., Skowron, P., Wolosz, A., Galan, A., Grzymala, K., Krajewska, M., Nowak, R., Kłos, M., Cruz, V., Castro, P., Ferro, J., Canhão, P., Gouveia, R., Inácio, N., Rodrigues, M., Rachão, A., Ionel, C., Pereira, L., Viana-Baptista, M., Machado, C., Fernandes, C., Sargento, J., Inácio, N., Timchenko, L., Mironova, J., Zhadan, O., Torgashova, A., Bazhenova, O., Barashenkova, M., Kireeva, M., Romadina, N., Stepanova, I., Lenskaya, L., Lukinykh, L., Vorontsova, T., Agafina, A., Fedorova, A., Yashina, A., Alasheev, A., Smolkin, A., Prazdnichkova, E., Lutskovich, O., Gonysheva, Y., Mordvintseva, E., Nechaev, A., Martynova, E., Fedoraeva, N., Vishnyakova, T., Popov, D., Merzliakova, A., Margarita, K., Rechkalova, L., Ilyina, A., Kurenkova, N., Barbarash, O., Bazdyrev, E., Zvereva, T., Hromova, A., Morkvenas, A., Postnikova, E., Kovalenko, G., Taran, I., Pavlov, L., Ott, M., Chernitsova, N., Vodopyanova, N., Drozdova, E., Korebo, E., Lobanova, M., Lazareva, N., Snegova, N., Nikolaeva, O., Kolesnikov, Y., Kosheleva, Y., Krastev, G., Tomasova, K., Danis, M., Mako, M., Jankovicova, Z., Stevkova, Z., Kovacik, M., Kubikova, T., Jarosova, A., Serdahely, V., Cilingova, I., Pribulova, I., Sedlak, J., Slebodova, K., Paldaufova, M., Risnovsky, R., Berndtova, B., Urbanova, I., Junas, R., Karapetian, S., Gurcik, L., Vantrobova, A., Verbovsky, F., Vanacka, K., Ferenc, M., Galik, P., Bucakova, S., Ferencova, M., Kubalova, P., Boksanska, Z., Zacharova, E., Mahundi, E., Judita, H., Bachnak, M., Turcani, P., Kvasnicova Kamenska, A., Jurik, M., Vestenicka, V., Kycina, M., Sagatova, E., Dvorak, M., Hlubekova, A., Kucera, C., Gernath, L., Ferenc, M., Frimmelova, P., Slebodnikova, J., Aksteinerova, N., Horny, V., Gregova, Z., Segura, T., Romero, C., Ayo, O., Masjuan Vallejo, J., Cruz, A., De felipe, A, Matute, M.C., Garcia, S., Tembl Ferrairo, J., Vielba, I., Morales Caba, L., Molina, C., Garcia-Tornel García-Camba, Á., Requena Ruiz, M., Noelia, R., Rodriguez-Yañez, M., Rodriguez Castro, E., Lopez, I., Santamaria, M., Arias, S., Purroy García, F., Vázquez Justes, D., Mauri Capdevila, G., Vicente Pascual, M., Martí Fabregas, J., Camps Renom, P., Rodríguez Campello, A., Giralt, E., Krupinski, J., Molina, J., Trillo Senin, C. Ramos Martin, S., De La Fuente Sanz, E., Moniche, F., Manuel, M.R., Pardo, B., Martínez, I., Hernández Pérez, M., Arenillas Lara, J.F., De Lera, M., Egido, J.A., Gomez Escalonilla, C., Guillan, M., Martinez, J., Lindgren, A., Andsberg, G., Wictor, L., Leonidou, M., Stenman, M., Dalberg, N., Laska, A.C., Grünfeldt, A., Lundström, A., Nadzjafov, E., Rooth, E., Dalenbring, I., Sandén, P., Johansson, E., Thomas, G., Zietz, A.V., Rudin, S., Dittrich, T.D., Lilian, K., Kägi, G., Vehoff, J., Arnold, M., Scutelnic, A., Clénin, L., Beyeler, M., Madlaine, M., Maamari, B., Siepen, B., Vynckier, J., Tarnutzer, A., Bertschi, D., Luciani, M., Cereda, C., Maulucci, F., Bianco, G., Shairin, S., Pihan, H.A., Salmen, S., Quinn, T., McAlpine, C., Wright, F., Kalladka, D., Taylor, E., Sohaa, J., Brown, Z., Dawson, J., Cameron, A., Muir, S., Dima, S., Khan, U., Zhang, L., Warburton, E., Chatterjee, K., Nallasivan, A., Curran, D., Haider, S., Ghani, U., Kenton, A., Dallol, B., Mirza, M., Menezes, B., Davies, R., Robinson, T.G., Manning, L., Sztriha, L., Phinney, T., Sethi, P., Altafullah, I., Sharaf, A., Ostrander, M., Renati, S., Burgin, W.S., Olds, K., Delio, P., Malek, A., Dissin, J., Khatri, P., Flaherty, M., Demel, S., and Dofitas, S.

Published
2024
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4. 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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5. Safety and Tolerability of Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy: Results of the ProCID Study.

Author

Cornblath, David R., van Doorn, Pieter A., Hartung, Hans-Peter, Merkies, Ingemar S. J., Katzberg, Hans D., Hinterberger, Doris, Clodi, Elisabeth, Kastrev, S., Rizova, V., Milanov, I., Massie, R., Taleb, R., Bednar, M., Ridzon, P., Schmidt, J., Zschüntzsch, J., Csilla, R., Vécsei, L., Rejdak, K., and Koszewicz, M.

Subjects
CHRONIC inflammatory demyelinating polyradiculoneuropathy, SAFETY, CONTACT dermatitis
Abstract

Background and Aims: The ProCID study evaluated the efficacy and safety of three doses of a 10% liquid intravenous immunoglobulin (IVIg) preparation (panzyga®) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This report describes the safety findings. Methods: Patients were randomised to receive a 2.0 g/kg induction dose followed by maintenance doses of either 0.5, 1.0 or 2.0 g/kg IVIg every 3 weeks over 24 weeks. Results: All 142 enrolled patients were included in the safety analyses. In total, 286 treatment-emergent adverse events (TEAEs) were reported in 89 patients, of which 173 (60.5%) were considered treatment-related. Most TEAEs were of mild severity. Eleven serious TEAEs were reported in 6 patients. Two serious TEAEs in one patient (headache and vomiting) were considered related to treatment, which resolved without study discontinuation. No treatment-related thrombotic events, haemolytic transfusion reactions or deaths occurred. One patient discontinued the study due to a TEAE (allergic dermatitis) probably related to IVIg. Headache was the only dose-dependent TEAE, with incidences ranging from 2.9 to 23.7%, the incidence of all other TEAEs was similar across treatment groups. Most TEAEs were associated with the induction dose infusion, and the rate of TEAEs decreased thereafter. The median (IQR) daily IVIg dose was 78 (64–90) g, and 94.4% of patients tolerated the maximal infusion rate of 0.12 ml/kg/min without pre-medication. Interpretation: Infusions of 10% IVIg at doses up to 2.0 g/kg with high infusion rates were safe and well tolerated in patients with CIDP. Clinical trial numbers: EudraCT 2015-005443-14, NCT02638207. [ABSTRACT FROM AUTHOR]

Published
2023
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6. Cognitive and Motor Decline in Dementia with Lewy Bodies and Parkinson's Disease Dementia

Author

Gonzalez MC, Tovar-Rios DA, Alves G, Dalen I, Williams-Gray CH, Camacho M, Forsgren L, Backstrom D, Lawson RA, Macleod AD, Counsell CE, Paquet C, DeLena C, D'Antonio F, Pilotto A, Padovani A, Blanc F, Falup-Pecurariu C, Lewis SJG, Rejdak K, Papuc E, Hort J, Nedelska Z, O'Brien J, Bonanni L, Marquie M, Boada M, Pytel V, Abdelnour C, Alcolea D, Beyer K, Tysnes O-B, Aarsland D, Maple-Grodem J

Published
2023
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7. Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Author

Leurs, CE, Twaalfhoven, HAM, Lissenberg-Witte, BI, van Pesch, V, Dujmovic, I, Drulovic, J, Castellazzi, M, Bellini, T, Pugliatti, M, Kuhle, J, Villar, LM, Alvarez-Cermeño, JC, Alvarez-Lafuente, R, Hegen, H, Deisenhammer, F, Walchhofer, LM, Thouvenot, E, Comabella, M, Montalban, X, Vécsei, L, Rajda, C, Galimberti, D, Scarpini, E, Altintas, A, Rejdak, K, Frederiksen, JL, Pihl-Jensen, G, Jensen, PEH, Khalil, M, Voortman, MM, Fazekas, F, Saiz, Albert, La Puma, D, Vercammen, M, Vanopdenbosch, L, Uitdehaag, BMJ, Killestein, J, Bridel, C, Teunissen, Charlotte E, Universitat Autònoma de Barcelona, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Basic (bio-) Medical Sciences, Ayşe, Altıntaş, Leurs, C.E., Twaalfhoven, H.A.M., Lissenberg-Witte, B.I., van Pesch, V., Dujmovic, I., Drulovic, J., Castellazzi, M., Bellini, T., Pugliatti, M., Kuhle, J., Villar, L.M., Alvarez-Cermeño, J.C., Alvarez-Lafuente, R., Hegen, H., Deisenhammer, F., Walchhofer, L.M., Thouvenot, E., Comabella, M., Montalban, X., Vécsei, L., Rajda, C., Galimberti, D., Scarpini, E., Rejdak, K., Frederiksen, J.L., Pihl-Jensen, G., Jensen, P.E.H., Khalil, M., Voortman, M.M., Fazekas, F., Saiz, A., La Puma, D., Vercammen, M., Vanopdenbosch, L., Uitdehaag, B.M.J., Killestein, J., Bridel, C., Teunissen, C., School of Medicine, Department of Neurology, Neurology, Laboratory Medicine, Epidemiology and Data Science, APH - Methodology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Department of Anatomy and Neurosciences [Amsterdam, The Netherlands] (Amsterdam Neuroscience), Section Clinical Neuroanatomy [Amsterdam, The Netherlands], VU University Medical Center [Amsterdam]-VU University Medical Center [Amsterdam], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Cliniques Universitaires Saint-Luc [Bruxelles], Clinical Centre of Serbia, Università degli Studi di Ferrara (UniFE), University Hospital Basel [Basel], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Red Española de Esclerosis Múltiple (REEM), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Department of Neurology, Medical University of Innsbruck, Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre d'Esclerosi Múltiple de Catalunya (CemCat), Vall d'Hebron University Hospital [Barcelona], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Szeged [Szeged], Centro Dino Ferrari [Milano], Università degli Studi di Milano [Milano] (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Koç University, Medical University of Lublin, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Danish Multiple Sclerosis Research Centre, Copenhagen University Hospital-Copenhagen University Hospital, Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Department of Neurology, AZ Sint Jan Brugge Oostende, Neuroscience Amsterdam, VU University Medical Centre, 1081HV 1117, Amsterdam, Amsterdam Neuroscience [Pays-Bas], and Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam]

Subjects
KFLC (kappa free light chain), Adult, Male, Multiple Sclerosis, Clinical Neurology, Esclerosi múltiple, CSF, CSF (cerebrospinal fluid), Immunoglobulin light chain, Sensitivity and Specificity, NO, Multiple sclerosis, Immunoglobulin kappa-Chains, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, Immunoglobulin lambda-Chains, Humans, Medicine, Diagnostic biomarker, biomarkers, KFLC, OCB, 030304 developmental biology, 0303 health sciences, business.industry, Biochemical markers, Oligoclonal Bands, Reproducibility of Results, Middle Aged, OCB (oligoclonal IgG band), Free Light Chain, Biomarkers, Neurology, Multicenter study, Marcadors bioquímics, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), business, Original Research Papers, 030217 neurology & neurosurgery, Kappa
Abstract

Objective: to validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: we performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: the cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS., NA

Published
2020

8. 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

13. Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Author

UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Leurs, CE, Twaalfhoven, HAM, Lissenberg-Witte, BI, Van Pesch, Vincent, Dujmovic, I, Drulovic, J, Castellazzi, M, Bellini, T, Pugliatti, M, Kuhle, J, Villar, LM, Alvarez-Cermeño, JC, Alvarez-Lafuente, R, Hegen, H, Deisenhammer, F, Walchhofer, LM, Thouvenot, E, Comabella, M, Montalban, X, Vécsei, L, Rajda, C, Galimberti, D, Scarpini, E, Altintas, A, Rejdak, K, Frederiksen, JL, Pihl-Jensen, G, Jensen, PEH, Khalil, M, Voortman, MM, Fazekas, F, Saiz, A, La Puma, D, Vercammen, M, Vanopdenbosch, L, Uitdehaag, BMJ, Killestein, J, Bridel, C, Teunissen, C, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Leurs, CE, Twaalfhoven, HAM, Lissenberg-Witte, BI, Van Pesch, Vincent, Dujmovic, I, Drulovic, J, Castellazzi, M, Bellini, T, Pugliatti, M, Kuhle, J, Villar, LM, Alvarez-Cermeño, JC, Alvarez-Lafuente, R, Hegen, H, Deisenhammer, F, Walchhofer, LM, Thouvenot, E, Comabella, M, Montalban, X, Vécsei, L, Rajda, C, Galimberti, D, Scarpini, E, Altintas, A, Rejdak, K, Frederiksen, JL, Pihl-Jensen, G, Jensen, PEH, Khalil, M, Voortman, MM, Fazekas, F, Saiz, A, La Puma, D, Vercammen, M, Vanopdenbosch, L, Uitdehaag, BMJ, Killestein, J, Bridel, C, and Teunissen, C

Abstract

OBJECTIVE: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). METHODS: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. RESULTS: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. CONCLUSION: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

Published
2020

14. Kappa free light chains is a valid tool in the diagnostics of MS:A large multicenter study

Author

Leurs, C. E., Twaalfhoven, H. A. M., Lissenberg-Witte, B. I., van Pesch, V., Dujmovic, I., Drulovic, J., Castellazzi, M., Bellini, T., Pugliatti, M., Kuhle, J., Villar, L. M., Alvarez-Cermeño, J. C., Alvarez-Lafuente, R., Hegen, H., Deisenhammer, F., Walchhofer, L. M., Thouvenot, E., Comabella, M., Montalban, X., Vécsei, L., Rajda, C., Galimberti, D., Scarpini, E., Altintas, A., Rejdak, K., Frederiksen, J. L., Pihl-Jensen, G., Jensen, P. E. H., Khalil, M., Voortman, M. M., Fazekas, F., Saiz, A., La Puma, D., Vercammen, M., Vanopdenbosch, L., Uitdehaag, B. M. J., Killestein, J., Bridel, C., Teunissen, C., Leurs, C. E., Twaalfhoven, H. A. M., Lissenberg-Witte, B. I., van Pesch, V., Dujmovic, I., Drulovic, J., Castellazzi, M., Bellini, T., Pugliatti, M., Kuhle, J., Villar, L. M., Alvarez-Cermeño, J. C., Alvarez-Lafuente, R., Hegen, H., Deisenhammer, F., Walchhofer, L. M., Thouvenot, E., Comabella, M., Montalban, X., Vécsei, L., Rajda, C., Galimberti, D., Scarpini, E., Altintas, A., Rejdak, K., Frederiksen, J. L., Pihl-Jensen, G., Jensen, P. E. H., Khalil, M., Voortman, M. M., Fazekas, F., Saiz, A., La Puma, D., Vercammen, M., Vanopdenbosch, L., Uitdehaag, B. M. J., Killestein, J., Bridel, C., and Teunissen, C.

Abstract

Objective: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

Published
2020

19. 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

23. 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

24. 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

25. 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

26. 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

27. Kappa free light chains is a valid tool in the diagnostics of MS: a large multicenter study

Author

Ayşe, Altıntaş, Leurs, C.E.; Twaalfhoven, H.A.M.; Lissenberg-Witte, B.I.; van Pesch, V.; Dujmovic, I.; Drulovic, J.; Castellazzi, M.; Bellini, T.; Pugliatti, M.; Kuhle, J.; Villar, L.M.; Alvarez-Cermeño, J.C.; Alvarez-Lafuente, R.; Hegen, H.; Deisenhammer, F.; Walchhofer, L.M.; Thouvenot, E.; Comabella, M.; Montalban, X.; Vécsei, L.; Rajda, C.; Galimberti, D.; Scarpini, E.; Rejdak, K.; Frederiksen, J.L.; Pihl-Jensen, G.; Jensen, P.E.H.; Khalil, M.; Voortman, M.M.; Fazekas, F.; Saiz, A.; La Puma, D.; Vercammen, M.; Vanopdenbosch, L.; Uitdehaag, B.M.J.; Killestein, J.; Bridel, C.; Teunissen, C., School of Medicine, Department of Neurology, Ayşe, Altıntaş, Leurs, C.E.; Twaalfhoven, H.A.M.; Lissenberg-Witte, B.I.; van Pesch, V.; Dujmovic, I.; Drulovic, J.; Castellazzi, M.; Bellini, T.; Pugliatti, M.; Kuhle, J.; Villar, L.M.; Alvarez-Cermeño, J.C.; Alvarez-Lafuente, R.; Hegen, H.; Deisenhammer, F.; Walchhofer, L.M.; Thouvenot, E.; Comabella, M.; Montalban, X.; Vécsei, L.; Rajda, C.; Galimberti, D.; Scarpini, E.; Rejdak, K.; Frederiksen, J.L.; Pihl-Jensen, G.; Jensen, P.E.H.; Khalil, M.; Voortman, M.M.; Fazekas, F.; Saiz, A.; La Puma, D.; Vercammen, M.; Vanopdenbosch, L.; Uitdehaag, B.M.J.; Killestein, J.; Bridel, C.; Teunissen, C., School of Medicine, and Department of Neurology

Abstract

Objective: to validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: we performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: the cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS., NA

Published
2019

30. Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome

Author

Disanto, G1, Adiutori, R2, Dobson, R2, Martinelli, V3, Dalla Costa G3, Runia, T4, Evdoshenko, E5, Thouvenot, E6, Trojano, M7, Norgren, N8, Teunissen, C9, Kappos, L10, Giovannoni, G2, Kuhle, J, Bianchi, L, Topping, J, Bestwick, Jp, Meier, Uc, Lazareva, N, Iaffaldano, P, Direnzo, V, Khademi, M, Piehl, F, Comabella, M, Sombekke, M, Killestein, J, Hegen, H, Rauch, S, D'Alfonso, S, Alvarez-Cermeño, Jc, Kleinová, P, Horáková, D, Roesler, R, Lauda, F, Llufriu, S, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Menge, T, Rajda, C, Bergamaschi, R, Moll, N, Khalil, M, Marignier, R, Dujmovic, I, Larsson, H, Malmestrom, C, Scarpini, E, Fenoglio, C, Wergeland, S, Laroni, A, Annibali, V, Romano, S, Martínez, Ad, Carra, A, Salvetti, M, Uccelli, A, Torkildsen, Ø, Myhr, Km, Galimberti, D, Rejdak, K, Lycke, J, Frederiksen, Jl, Drulovic, J, Confavreux, C, Brassat, D, Enzinger, C, Fuchs, S, Bosca, I, Pelletier, J, Picard, C, Colombo, E, Franciotta, D, Derfuss, T, Lindberg, Rl, Yaldizli, Ö, Vécsei, L, Kieseier, Bc, Hartung, Hp, Villoslada, P, Siva, A, Saiz, A, Tumani, H, Havrdová, E, Villar, Lm, Leone, M, Barizzone, N, Deisenhammer, F, Montalban, X, Tintoré, M, Olsson, T, Lehmann, S, Castelnovo, G, Lapin, S, Hintzen, R, Furlan, R, Comi, G, Ramagopalan, Sv., Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Laboratory Medicine, Amsterdam Neuroscience - Neuroinfection & -inflammation, Disanto, G., Adiutori, R., Dobson, R., Martinelli, V., Dalla Costa, G., Runia, T., Evdoshenko, E., Thouvenot, E., Trojano, M., Norgren, N., Teunissen, C., Kappos, L., Giovannoni, G., Kuhle, J., on behalf of the International ClinicallyIsolated Syndrome Study, Group, and Neurology

Subjects
Male, Pathology, Future studies, Gastroenterology, 0302 clinical medicine, Neurofilament Proteins, Multiple Sclerosi, 0303 health sciences, Clinically isolated syndrome, medicine.diagnostic_test, Medicine (all), Neurofilament Protein, Demyelinating Disease, Magnetic Resonance Imaging, Psychiatry and Mental Health, Predictive value of tests, Disease Progression, Biomarker (medicine), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Human, Adult, medicine.medical_specialty, Multiple Sclerosis, Neurofilament light, multiple sclerosis, adult, axons, biomarkers, demyelinating diseases, disease progression, female, follow-up studies, humans, magnetic resonance imaging, male, neurofilament proteins, predictive value of tests, neurology (clinical), psychiatry and mental health, surgery, arts and humanities (miscellaneous), medicine (all), [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Axon, Follow-Up Studie, 03 medical and health sciences, Arts and Humanities (miscellaneous), Predictive Value of Tests, Internal medicine, medicine, Humans, In patient, MULTIPLE SCLEROSIS, 030304 developmental biology, business.industry, Multiple sclerosis, Magnetic resonance imaging, Biomarker, medicine.disease, Axons, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, Demyelinating Diseases, Follow-Up Studies
Abstract

International audience; BACKGROUND:Neurofilament light chain (NfL) represents a promising biomarker for axonal injury. We present the first exploratory study on serum NfL in patients with a clinically isolated syndrome (CIS) and healthy controls.METHODS:We investigated serum NfL levels in 100 patients with CIS with a short conversion interval to clinically definite multiple sclerosis (MS) (fast converters (FC), median (IQR) conversion time: 110 days (79-139)); 98 patients with non-converting CIS (non-converters (NC), follow-up: 6.5 years (5.3-7.9)); and 92 healthy controls.RESULTS:NfL levels were higher in FC (24.1 pg/mL (13.5-51.8)) and NC (19.3 pg/mL (13.6-35.2)) than in healthy controls (7.9 pg/mL (5.6-17.2)) (OR=5.85; 95% CI 2.63 to 13.02; p = 1.5 × 10(-5) and OR = 7.03; 95% CI 2.85 to 17.34; p = 2.3 × 10(-5), respectively). When grouping FC and NC, increased serum NfL concentration was also associated with increasing numbers of T2 hyperintense MRI lesions (OR = 2.36; 95% CI 1.21 to 4.59; p = 0.011), gadolinium-enhancing lesions (OR = 2.69; 95% CI 1.13 to 6.41; p=0.026) and higher disability scores (OR = 2.54; 95% CI 1.21 to 5.31; p = 0.013) at CIS diagnosis.CONCLUSIONS:If replicated in future studies, serum NfL may represent a reliable and easily accessible biomarker of early axonal damage in CIS and MS.

Published
2016

35. Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Author

Leurs, CE, primary, Twaalfhoven, HAM, additional, Lissenberg-Witte, BI, additional, van Pesch, V, additional, Dujmovic, I, additional, Drulovic, J, additional, Castellazzi, M, additional, Bellini, T, additional, Pugliatti, M, additional, Kuhle, J, additional, Villar, LM, additional, Alvarez-Cermeño, JC, additional, Alvarez-Lafuente, R, additional, Hegen, H, additional, Deisenhammer, F, additional, Walchhofer, LM, additional, Thouvenot, E, additional, Comabella, M, additional, Montalban, X, additional, Vécsei, L, additional, Rajda, C, additional, Galimberti, D, additional, Scarpini, E, additional, Altintas, A, additional, Rejdak, K, additional, Frederiksen, JL, additional, Pihl-Jensen, G, additional, Jensen, PEH, additional, Khalil, M, additional, Voortman, MM, additional, Fazekas, F, additional, Saiz, A, additional, La Puma, D, additional, Vercammen, M, additional, Vanopdenbosch, L, additional, Uitdehaag, BMJ, additional, Killestein, J, additional, Bridel, C, additional, and Teunissen, C, additional

Published
2019
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37. Axonal degeneration and inflammationin acute optic neuritis

Author

Petzold, A., Rejdak, K., and Plant, G.T.

Subjects
Optic neuritis -- Research, Optic neuritis -- Physiological aspects, Optic neuritis -- Diagnosis, Nervous system -- Degeneration, Nervous system -- Research, Nervous system -- Physiological aspects, Health, Psychology and mental health
Published
2004

38. Epstein-Barr-negative MS: a true phenomenon?

Author

Dobson, Ruth, Kuhle, Jens, Middeldorp, Jaap, Giovannoni, Gavin, on behalf of the international CIS study investigators including Dalla Costa, G, Furlan, R, Martinelli, V, Comi, G, Runia, T, Hintzen, R, Evdoshenko, E, Lazareva, N, Lapin, S, Thouvenot, E, Lehmann, S, Castelnovo, G, Iaffaldano, P, Direnzo, V, Trojano, M, Khademi, . M, Piehl, F, Olsson, T, Comabella, M, Montalban, X, Tintoré, M, Sombekke, M, Killestein, J, Teunissen, C, Hegen, H, Deisenhammer, F, Rauch, S, D'Alfonso, S, Barizzone, N, Alvarez Cermeño, Jc, Villar, Lm, Kleinová, P, Horáková, D, Havrdová, E, Roesler, R, Lauda, F, Tumani, H, Llufriu, S, Villoslada, P, Saiz, A, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Siva, A, Menge, T, Kieseier, Bc, Hartung, Hp, Rajda, C, Vécsei, L, Bergamaschi, R, Colombo, E, Franciotta, D, Moll, N, Pelletier, J, Picard, C, Khalil, M, Enzinger, C, Fuchs, S, Marignier, R, Confavreux, C, Dujmovic, I, Drulovic, J, Larsson, H, Malmestrom, C, Lycke, J, Scarpini, E, C. Fenoglio, C, Galimberti, D, Wergeland, S, Torkildsen, Ø, Myhr, Km, Laroni, Alice, Uccelli, Antonio, Annibali, V, Romano, S, Salvetti, M, Martínez, Ad, Carra, A, Rejdak, K, Frederiksen, Jl, Brassat, D, Bosca, I, Casanova, B, Derfuss, T, Lindberg, R, Yaldizli, Ö, Kappos, L, Leone, M., and Pathology

Subjects
0301 basic medicine, business.industry, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Neurology, Epstein barr, Phenomenon, Medicine, Neurology (clinical), business, Competence (human resources), Social psychology, Clinical/Scientific Notes, 030217 neurology & neurosurgery
Abstract

This work was supported by institutional funding and in part by the BMBF grant KKNMS (Competence Net Multiple Sclerosis) to H Tumani.

Published
2017

39. Cladribine in myasthenia gravis: a pilot open‐label study.

Author

Rejdak, K., Szklener, S., Korchut, A., and Baranowski, D.

Subjects
*MYASTHENIA gravis, *PILOT projects, *LONGITUDINAL method, *ADVERSE health care events, *TREATMENT effectiveness
Abstract

Background and purpose: The aim of this study was to assess the effectiveness of cladribine treatments in a population of patients with refractory myasthenia gravis (MG). Methods: In a prospective open‐label study of cladribine in refractory MG, 13 patients received cladribine at baseline with repetitive cycles driven by clinical response. A Myasthenia Gravis Composite (MGC) score was obtained and a standard dose of steroids was administered. Results: A total of 11 patients achieved significant clinical improvement in MGC score during their therapy. The mean MGC score declined from 15.1 to 6.3 points within 4 months of observation. The dosage of prednisolone declined from 9.5 to 1.9 mg. None of the patients required intravenous immunoglobulin or plasma exchange treatments and no adverse events occurred in the study period. Conclusion: Cladribine seems to be a safe and effective emergency therapy in a population of patients with refractory MG. [ABSTRACT FROM AUTHOR]

Published
2020
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40. Convulsive status epilepticus management in adults and children: Report of the Working Group of the Polish Society of Epileptology

Author

Jędrzejczak, J., primary, Mazurkiewicz-Bełdzińska, M., additional, Szmuda, M., additional, Majkowska-Zwolińska, B., additional, Steinborn, B., additional, Ryglewicz, D., additional, Owczuk, R., additional, Bartkowska-Śniatkowska, A., additional, Widera, E., additional, Rejdak, K., additional, Siemiński, M., additional, and Nagańska, E., additional

Published
2018
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41. 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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44. Conversion from clinically isolated syndrome to multiple sclerosis:A large multicentre study

Author

Kuhle, J, Disanto, G, Dobson, R, Adiutori, R, Bianchi, L, Topping, J, Bestwick, J P, Meier, U-C, Marta, M, Dalla Costa, G, Runia, T, Evdoshenko, E, Lazareva, N, Thouvenot, E, Iaffaldano, P, Direnzo, V, Khademi, M, Piehl, F, Comabella, M, Sombekke, M, Killestein, J, Hegen, H, Rauch, S, D'Alfonso, S, Alvarez-Cermeño, J C, Kleinová, P, Horáková, D, Roesler, R, Lauda, F, Llufriu, S, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Menge, T, Rajda, C, Bergamaschi, R, Moll, N, Khalil, M, Marignier, R, Dujmovic, I, Larsson, H, Malmestrom, C, Scarpini, E, Fenoglio, C, Wergeland, S, Laroni, A, Annibali, V, Romano, S, Martínez, A D, Carra, A, Salvetti, M, Uccelli, A, Torkildsen, Ø, Myhr, K M, Galimberti, D, Rejdak, K, Lycke, J, Fredriksen, Jette Lautrup, Drulovic, J, Confavreux, C, Brassat, D, Enzinger, C, Fuchs, S, Bosca, I, Pelletier, J, Picard, C, Colombo, E, Franciotta, D, Derfuss, T, Lindberg, Rlp, Yaldizli, Ö, Vécsei, L, Kieseier, B C, Hartung, H P, Villoslada, P, Siva, A, Saiz, A, Tumani, H, Havrdová, E, Villar, L M, Leone, M, Barizzone, N, Deisenhammer, F, Teunissen, C, Montalban, X, Tintoré, M, Olsson, T, Trojano, M, Lehmann, S, Castelnovo, G, Lapin, S, Hintzen, R, Kappos, L, Furlan, R, Martinelli, V, Comi, G, Ramagopalan, S V, Giovannoni, G, Kuhle, J, Disanto, G, Dobson, R, Adiutori, R, Bianchi, L, Topping, J, Bestwick, J P, Meier, U-C, Marta, M, Dalla Costa, G, Runia, T, Evdoshenko, E, Lazareva, N, Thouvenot, E, Iaffaldano, P, Direnzo, V, Khademi, M, Piehl, F, Comabella, M, Sombekke, M, Killestein, J, Hegen, H, Rauch, S, D'Alfonso, S, Alvarez-Cermeño, J C, Kleinová, P, Horáková, D, Roesler, R, Lauda, F, Llufriu, S, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Menge, T, Rajda, C, Bergamaschi, R, Moll, N, Khalil, M, Marignier, R, Dujmovic, I, Larsson, H, Malmestrom, C, Scarpini, E, Fenoglio, C, Wergeland, S, Laroni, A, Annibali, V, Romano, S, Martínez, A D, Carra, A, Salvetti, M, Uccelli, A, Torkildsen, Ø, Myhr, K M, Galimberti, D, Rejdak, K, Lycke, J, Fredriksen, Jette Lautrup, Drulovic, J, Confavreux, C, Brassat, D, Enzinger, C, Fuchs, S, Bosca, I, Pelletier, J, Picard, C, Colombo, E, Franciotta, D, Derfuss, T, Lindberg, Rlp, Yaldizli, Ö, Vécsei, L, Kieseier, B C, Hartung, H P, Villoslada, P, Siva, A, Saiz, A, Tumani, H, Havrdová, E, Villar, L M, Leone, M, Barizzone, N, Deisenhammer, F, Teunissen, C, Montalban, X, Tintoré, M, Olsson, T, Trojano, M, Lehmann, S, Castelnovo, G, Lapin, S, Hintzen, R, Kappos, L, Furlan, R, Martinelli, V, Comi, G, Ramagopalan, S V, and Giovannoni, G

Abstract

BACKGROUND AND OBJECTIVE: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort.METHODS: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS.RESULTS: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres.CONCLUSIONS: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

Published
2015

50. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study

Author

Kuhle, J, primary, Disanto, G, additional, Dobson, R, additional, Adiutori, R, additional, Bianchi, L, additional, Topping, J, additional, Bestwick, JP, additional, Meier, U-C, additional, Marta, M, additional, Costa, G Dalla, additional, Runia, T, additional, Evdoshenko, E, additional, Lazareva, N, additional, Thouvenot, E, additional, Iaffaldano, P, additional, Direnzo, V, additional, Khademi, M, additional, Piehl, F, additional, Comabella, M, additional, Sombekke, M, additional, Killestein, J, additional, Hegen, H, additional, Rauch, S, additional, D’Alfonso, S, additional, Alvarez-Cermeño, JC, additional, Kleinová, P, additional, Horáková, D, additional, Roesler, R, additional, Lauda, F, additional, Llufriu, S, additional, Avsar, T, additional, Uygunoglu, U, additional, Altintas, A, additional, Saip, S, additional, Menge, T, additional, Rajda, C, additional, Bergamaschi, R, additional, Moll, N, additional, Khalil, M, additional, Marignier, R, additional, Dujmovic, I, additional, Larsson, H, additional, Malmestrom, C, additional, Scarpini, E, additional, Fenoglio, C, additional, Wergeland, S, additional, Laroni, A, additional, Annibali, V, additional, Romano, S, additional, Martínez, AD, additional, Carra, A, additional, Salvetti, M, additional, Uccelli, A, additional, Torkildsen, Ø, additional, Myhr, KM, additional, Galimberti, D, additional, Rejdak, K, additional, Lycke, J, additional, Frederiksen, JL, additional, Drulovic, J, additional, Confavreux, C, additional, Brassat, D, additional, Enzinger, C, additional, Fuchs, S, additional, Bosca, I, additional, Pelletier, J, additional, Picard, C, additional, Colombo, E, additional, Franciotta, D, additional, Derfuss, T, additional, Lindberg, RLP, additional, Yaldizli, Ö, additional, Vécsei, L, additional, Kieseier, BC, additional, Hartung, HP, additional, Villoslada, P, additional, Siva, A, additional, Saiz, A, additional, Tumani, H, additional, Havrdová, E, additional, Villar, LM, additional, Leone, M, additional, Barizzone, N, additional, Deisenhammer, F, additional, Teunissen, C, additional, Montalban, X, additional, Tintoré, M, additional, Olsson, T, additional, Trojano, M, additional, Lehmann, S, additional, Castelnovo, G, additional, Lapin, S, additional, Hintzen, R, additional, Kappos, L, additional, Furlan, R, additional, Martinelli, V, additional, Comi, G, additional, Ramagopalan, SV, additional, and Giovannoni, G, additional

Published
2015
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