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I. Chang, M. Novas, J. Rana, J. Marantz, E. Ehler, R. Taláb, H. Hartung, A. Csányi, L. Csiba, G. Jakab, R. Hintzen, H. Kwiecinski, Z. Maciejek, A. Belova, A. N. Boiko, A. Elchaninov, V. Kozlov, M. Odinak, S. Shvarkov, A. Skoromets, I. Stolyarov, O. Vorobieva, I. Zavalishin, J. Hillert, T. Olsson, M. Eraksoy, R. Karabudak, A. Siva, M. Sharief, C. Confavreux, J. Ware, M. Barnett, M. Paine, J. Lechner-Scott, R. Beran, C. Chapman, R. Schwartz, H. Butzkueven, R. Casse, R. Macdonell, T. Berger, F. Fazekas, G. Ransmayr, K. Vass, S. Belachew, P. D. de Deyn, B. Dubois, R. Medaer, P. Seeldrayers, L. Vanopdenbosch, V. Bhan, J. Bouchard, S. Christie, P. Grammond, F. Jacques, G. Vorobeychik, V. Brinar, V. Demarin, Z. Ambler, P. Kaňovský, E. Meluzínová, I. Rektor, O. Škoda, Marta Vachová Duchcovská, Pierre Clavelou Antoanela, I. Coman, C. Confavreux, G. Edan, O. Gout, C. Lebrun-Frénay, Anne-Caroline Papeix, P. Vermersch, K. Bachus-Banaschak, M. Berghoff, Florian Bethke, A. Chan, H. Diener, B. Griewing, J. Haas, C. Heesen, A. Hufnagel, F. Heidenreich, Silke Marckmann-Böenke, M. Marziniak, T. Rosenkranz, H. Schneider, V. Siefjediers, J. Springub, M. Stangel, F. Stögbauer, F. Bergh, K. Tinschert, N. Grigoriadis, A. Kyritsis, A. Papadimitriou, Luis Fernando Salguero Gonzalez, D. Chon, Hugo Alfredo Ordoñez Sarg, C. Agrawal, Velmurugendran Cu, S. Dwivedee, S. Kothari, Rahul Kulkarni, S. Kushwaha, A. Meena, M. Mehndiratta, Subhash Chandra Mukherjee, L. Pandit, Arun B. Shah, R. Shukla, K. Vijayan, A. Achiron, S. Flechter, R. Milo, A. Vaknin-Dembinsky, C. Pozzilli, Freddy Guillermo Castro Farfan, R. Rangel Guerra, Ildefonso Rodríguez-Leyva, J. L. Oropeza de Alba, R. A. Revilla, J. F. Rivera, E. Sanders, R. Hupperts, D. Mason, E. Willoughby, A. Băjenaru, F. Mureșanu, S. Nica, M. Simu, D. Obradovic, V. Krajn̆ák, F. Badenhorst, Judy Green, J. Heckmann, Michael Isaacs, M. Linnebank, S. Müller, M. Duddy, C. Hawkins, R. Nicholas, Jacqueline Palace, B. Sharrack, E. Silber, B. Turner, A. Camac, W. Chumley, H. Crayton, S. Dixit, J. English, N. Gordon, Lawrence P Goldstick, P. Gottschalk, E. Grazioli, W. Grainger, Barbara Green, B. Grelinger, Ajay Gupta, G. Hayat, B. Hendin, L. Henson, A. Hentati, C. Herrman, A. Itkin, T. Janus, L. Kasper, E. Lathi, E. Mowry, Gareth Parry, P. Riskind, S. Rizvi, H. Rossman, T. Scott, S. Shafer, J. Storey, B. Thrower, M. Rossen, William A. Tosches, Lori Trefts, A. Turel, R. Gold, L. Kappos, D. Arnold, G. Giovannoni, K. Dawson, P. Gallacher, C. Milla, P. Kowey, C. Kneebone, A. Fedulau, S. Likhachev, E. Mikhailova, Halina Naumova, D. Decoo, C. Sindic, L. Gaer, S. Grgić, O. Sinanović, E. Suljic, N. Deleva, D. Georgiev, L. Haralanov, S. Ivanova, I. Manchev, D. Minchev, P. Stamenova, I. Tournev, Elena Vacheva, Z. Zahariev, Roberto Vargas Howell, Alexander Parajeles Vindas, A. Bar-Or, G. Blevins, M. Kremenchutzky, Felix Veloso, Norbert Witt, M. Habek, J. Rudež, S. Soldo-Butković, R. B. Vurdelja, D. Doležil, Jiří Nova'k, D. Václavík, K. Antsov, K. Gross-Paju, S. Haldre, Alla Palu, T. Toomsoo, Abdullatif Al Khedr, W. Camu, J. de Seze, M. Debouverie, G. Defer, P. Labauge, T. Moreau, L. Rumbach, Klemens Angnstwurm, H. Benes̆, A. Berthele, H. Boldt, A. Christopher, T. Derfuss, I. Eisensehr, Peter Emrich, W. Feneberg, F. Hoffmann, R. Hohlfeld, Reinhard Hüntemann, B. Kallmann, B. Kieseier, I. Kleiter, H. Landefeld, W. Lüer, S. Masri, M. Mäurer, G. Nelles, P. Oschmann, C. Paschen, G. Reifschneider, M. Sailer, S. Schimrigk, Mechthild Spiegel-Meixensberger, A. Steinbrecher, B. Storch‐Hagenlocher, B. Tackenberg, K. Tiel‐Wilck, C. Karageorgiou, P. Papathanasopoulos, T. Thomaides, N. Vlaikidis, D. Arjundas, M. Behari, S. Shah, Amitabha Ghosh, Pahari Ghosh, N. Ichaporia, D. Khurana, Rahul Kulkarni, M. Mehndiratta, Neeta Mehta, U. Misra, J. Mukherji, Shankara Nellikunja, S. Radhakrishnan, A. Salem, P. Sethi, Gagandeep Singh, Civil Lines, M. Singh, Y. Singh, R. Srinivasa, K. Vijayan, B. Sweeney, R. Gilad, R. Shahien, M. Metra, A. Paegle, V. Daskalovska, Cesar M. Delgado, J. Escamilla, B. Estañol, N. López, M. Macias, G. Punzo, S. Quiñones, M. Rentería, Chihuahua’ Jose Santos, M. Gavriliuc, S. Groppa, O. Odainic, P. Timmings, A. Członkowska, M. Dorobek, W. Drozdowski, W. Fryze, H. Hertmanowska, A. Kaminska, Magdalena Kapelusiak-Pielok, Magdalena Kleczkowska, J. Kochanowicz, H. Kwiecinski, J. Losy, P. Nowacki, W. Nyka, K. Pierzchala, R. Podemski, A. Potemkowski, K. Selmaj, Z. Stelmasiak, A. Szczudlik, A. Tutaj, A. Wajgt, T. Zieliński, Á. Chinea, R. Bălaşa, V. Ionescu-Dimancea, P. Mihancea, Cristian Popescu, Liviu Codrut Protosevici, S. M. Drakulić, Č. Nadj, R. Raičević, S. Vojinović, Edita Kahancová, E. Kurča, L. Lisý, P. Turčáni, R. Arroyo, Ó. Fernández, C. Guijarro, G. Izquierdo, X. Montalban, C. Oreja-Guevara, J. Prieto, F. S. Lopez, Nataliya Buchakchyys'ka, Galyna Chmyr, A. Goloborodko, N. Grytsay, T. Kobys, G. Kushnir, V. Lebedynets, N. Lytvynenko, S. Moskovko, T. Nehrych, B. Palamar, Igor Pasyura, T. Ryabichenko, N. Voloshina, M. Apperson, Angela Applebee, S. Asher, R. Ayala, D. Ayres, S. Azizi, M. Baker, Brendan Bauer, R. Bomprezzi, R. Buckler, W. Carlini, S. Cohan, Giles Crowell, K. Edwards, Geoffery Eubank, W. Felton, P. Fodor, J. Foley, C. Ford, M. Forester, E. Fox, R. Fox, S. Freedman, G. Garmany, S. Gazda, D. Giang, B. Glaun, S. Gold, M. Gottesman, Mark Gudesblatt, J. Herbert, A. Herskowitz, W. Honeycutt, J. Huddlestone, R. Hull, S. Hunter, G. Hutton, D. Jacobs, M. Janicki, B. Khatri, R. Kinkel, S. Krolczyk, L. Krupp, C. Laganke, M. Levin, Jonathan M. Licht, C. Luzzio, S. Lynch, D. Mattson, D. Mikol, T. Miller, A. Minagar, Galen Mitchell, H. Moses, Donald Negroski, Stephen Newman, G. Pardo, Malti J. Patel, A. Perel, J. Phillips, M. Picone, K. Rammohan, T. H. Rao, J. Rinker, S. Sadiq, J. Schaeffer, W. Sheremata, Robert K Shin, R. Shubin, S. Silverman, Robert Smith, L. Stein, Michael Stein, David F Steiner, B. Steingo, H. Sullivan, W. Sunter, A. Vaishnav, A. Vásquez, J. Voci, J. Warach, B. Weinstock-Guttman, M. Williams, S. Wray, R. Fox, J. Phillips, M. Hutchinson, E. Havrdová, M. Kita, Kate Wilson, Minhua Yang, K. Dawson, J. Antel, J. Ware, C. Polman, P. Kowey, Raymond Chung, G. Bakris, J. Richert, Burt Seibert, D. Brandes, D. Brassat, B. Cohen, R. Diem, M. Goldman, R. Herndon, Aaron E Miller, H. Tumani, Teresa Alfaro-Vidal, C. Crespo, J. Foster, K. Hunter, A. Garcia-Gomez, D. MacManus, David H. Miller, V. Santana, D. Tozer, Claudia Kingshott-Wheeler, T. Yousry
95 1. 4. 2016.

Characterizing absolute lymphocyte count profiles in dimethyl fumarate–treated patients with MS

Background:Delayed-release dimethyl fumarate (DMF), indicated for the treatment of patients with relapsing-remitting multiple sclerosis (MS), is a disease-modifying therapy with potential immunomodulatory and neuroprotective effects. In clinical trials, DMF was associated with reduced white blood cell and absolute lymphocyte counts. Current US prescribing information recommends obtaining a complete blood count, including absolute lymphocyte count (ALC), before initiating and during DMF treatment. Methods:We conducted an integrated analysis of phase 2b/3/long-term extension studies of DMF in MS (N = 2,470) to characterize ALC profiles. Results:Mean ALCs decreased by 30% during the first year and then plateaued, remaining above the lower limit of normal (LLN). Among patients treated ≥6 months (N = 2,099), 2.2% experienced ALCs <500 mm3 persisting ≥6 months. ALCs remained ≥LLN in 84% and 76% of patients during the first 6 and 12 months, respectively; of these, 0.1% and 0%, respectively, developed ALCs <500 mm3 persisting ≥6 months at any time. Evidence of ALC improvement following DMF discontinuation was observed. DMF efficacy was not substantially different in patients with and without lymphopenia. Conclusion:Lymphocyte monitoring provides effective means for early identification of patients at risk for developing severe, prolonged lymphopenia.


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