@article{854e16b63d0849308c892a402d420eb4,
title = "Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring",
abstract = "Natalizumab is a new treatment option for patients with active relapsing-remitting multiple sclerosis. In phase III studies, natalizumab was highly effective and well tolerated; however, three cases of progressive multifocal leucoencephalopathy (PML) were identified (estimated incidence of one per 1000; 95% CI 0·2-2·8; mean treatment period 17·9 months). In this Review we summarise the current information on PML, the three confirmed cases of PML, and the results of an extensive safety assessment of all patients treated with natalizumab. On the basis of these reviews, we make recommendations for appropriate selection of candidates for natalizumab and pretreatment assessments. In addition, a three-step diagnostic and management algorithm was developed to monitor natalizumab-treated patients with multiple sclerosis for PML and other opportunistic infections. The algorithm includes strategies for clinical, MRI, and laboratory assessments. Maintaining clinical vigilance allows for early suspension of natalizumab in potential cases of PML, thereby increasing the opportunity for immune reconstitution, which may improve prognosis if PML is confirmed.",
author = "Ludwig Kappos and David Bates and Hartung, {Hans Peter} and Eva Havrdova and David Miller and Polman, {Chris H.} and Mads Ravnborg and Hauser, {Stephen L.} and Rudick, {Richard A.} and Weiner, {Howard L.} and O'Connor, {Paul W.} and John King and Radue, {Ernst Wilhelm} and Tarek Yousry and Major, {Eugene O.} and Clifford, {David B.}",
note = "Funding Information: This consensus paper was proposed by LK and CHP and is based on meetings by several independent committees composed of lead investigators of the clinical studies with natalizumab in multiple sclerosis, and additional experts in the field of multiple sclerosis, PML, and natalizumab in Europe, the USA, Canada, and Australia. The authors thank the participants in these committees for their valuable input, especially the participants of the International Multiple Sclerosis Expert Forum (IMSEF), a group of experts established by Biogen Idec to provide guidance on the indication and necessary precautions of treatment with natalizumab in multiple sclerosis. Meetings of the IMSEF and the other committees were supported by Biogen Idec. We thank Verena Rohrer for assistance with preparation of the manuscript. Jillian Licata, Candace Lundin, and Nancy Bormann, employees of Thomson Scientific Connexions, also helped with the language editing of this manuscript but did not have any influence on its content. Their activities were funded by Biogen Idec. Funding Information: The authors disclose the following conflicts of interest: LK discloses that the University Hospital, Basel, has received research support from Biogen Idec, GlaxoSmithKline, Novartis Pharmaceuticals, Sanofi-Aventis, Schering, Serono, Teva Pharmaceuticals, and Wyeth Pharmaceuticals. LK has been principal investigator, member, or chair of steering committees or advisory boards in multiple sclerosis clinical trials sponsored by Abbott Laboratories, Bayer, Bayhill, Berlex, Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Centocor, Eisai, Elan Pharmaceuticals, Genzyme, GlaxoSmithKline, Immune Response, Neurocrine, Novartis Pharmaceuticals, Sanofi-Aventis, Schering, Serono, Roche, Teva Pharmaceuticals, UCB Pharma, and Wyeth, and has received lecture fees from one or more of these companies. Payments and consultancy fees were exclusively used for the support of research activities. DB has received honoraria and research support from Biogen Idec, Serono, Schering, and Teva Pharmaceuticals. H-PH has received honoraria and consultancy fees from, and participated as an investigator in phase II and III trials for, Biogen Idec, Bayer Vital, Schering, Serono, and Teva Pharmaceuticals. H-PH has received research grant support from Biogen Idec. EH has received clinical study research funding from Biogen Idec, Novartis Pharmaceuticals, Octapharma, Schering, Serono, and Teva Pharmaceuticals. She has received honoraria for symposium lectures from Biogen Idec, Pfizer, Schering, and Teva Pharmaceuticals. DM has received grant support from Biogen Idec, Elan, Schering, and GlaxoSmithKline for performance of MRI analyses in clinical trials, as well as honoraria for advisory or consultancy work, lectures, and related travel expenses from Aventis, Biogen Idec, Bristol Myers Squibb, GlaxoSmithKline, Schering, Serono, UCB Pharma, and Wyeth. CHP has received consultancy fees from Biogen Idec, Schering AG, Teva Pharmaceuticals, Serono, Novartis Pharmaceuticals, GlaxoSmithKline, and Antisense Therapeutics, lecture fees from Biogen Idec, Schering AG, and Teva Pharmaceuticals, and grant support from Biogen Idec, Schering AG, Wyeth, Novartis Pharmaceuticals, and GlaxoSmithKline. MR has received travel grants and consultancy fees from Aventis, Biogen Idec, Coloplast, and Schering. SLH has received a research grant from Biogen Idec for neurodegenerative disease research. RAR discloses that the Cleveland Clinic has received research support from Biogen Idec. RAR was principal investigator for the SENTINEL trial, which was supported by Biogen Idec. HLW has received consultancy fees from Autoimmune, Biogen Idec, Pepgen, Pfizer, Serono, Teva Pharmaceuticals, and Vascular Biogenics. PWO has served as a consultant for and received research trial grant support from Biogen Idec. JK has received honoraria and consultancy fees from Biogen Idec, Sanofi-Aventis, Schering, and Serono. EWR has received grant support from Biogen Idec, Schering, Novartis, Sanofi-Aventis, and GlaxoSmithKline for assessment of multicentre multiple sclerosis studies. Payments for advisory board and steering committee membership as well as speaker honoraria by the above mentioned companies to EWR were exclusively used for research projects at the Department of Neuroradiology. TY received support to perform MRI analyses through a research grant from Biogen Idec to the Institute of Neurology. EOM has no relationships to disclose. DBC has received payment as a consultant by Biogen Idec, Genzyme, Millennium, Pfizer, and Schering-Plough, and as a speaker by Boehringer-Ingelheim and Bristol-Myers Squibb. DBC has received research support from Bavarian Nordic, NeurogesX, Pfizer, Roche, Savient Pharmaceuticals, and Tibotec. ",
year = "2007",
month = may,
doi = "10.1016/S1474-4422(07)70078-9",
language = "English",
volume = "6",
pages = "431--441",
journal = "Lancet Neurology",
issn = "1474-4422",
number = "5",
}