J Neurol (2012) 259:1814–1823 DOI 10.1007/s00415-012-6414-9 O R I G I N A L C O M M U N I C A T I O N Natalizumab treatment of multiple sclerosis in Spain: results of an extensive observational study O. Ferna´ ndez • C. Oreja-Guevara • R. Arroyo • G. Izquierdo • J. L. Pe´rez • X. Montalban Received: 6 September 2011 / Revised: 3 January 2012 / Accepted: 6 January 2012 / Published online: 31 January 2012 The Author(s) 2012. This article is published with open access at Springerlink.com Abstract Natalizumab has been shown to be effective in pivotal clinical trials in multiple sclerosis; however, the patients in whom treatment is indicated in clinical practice have a different clinical proﬁle from those included in the clinical trials. The aim of this study is therefore to collect data on natalizumab use in everyday clinical practice in Spain. The 86 participating centers throughout Spain sub- mitted data on disease characteristics at baseline and after treatment. Valid data were available for 1,364 patients (69.3% women, 86.9% with relapsing–remitting disease). On behalf of the Spanish Experience with Natalizumab Study Group (GEXNE). The members of the GEXNE group are listed in appendix. O. Ferna´ndez (&) Institute of Clinical Neurosciences, Carlos Haya Regional University Hospital, Avenida Carlos Haya s/n, 29010 Ma´laga, Spain e-mail: oscar.fernandez.sspa@juntadeandalucia.es C. Oreja-Guevara Multiple Sclerosis Unit, La Paz University Hospital, Madrid, Spain R. Arroyo Multiple Sclerosis Unit, San Carlos Clinic Hospital, Madrid, Spain G. Izquierdo Neurology Department, Virgen Macarena University Hospital, Seville, Spain J. L. Pe´rez Neurology, Sierrallana Hospital, Torrelavega, Cantabria, Spain X. Montalban Neuroimmunology Unit, Vall d’Hebron University Hospital, Barcelona, Spain 123 Ninety-three percent had received prior therapy for multiple sclerosis. For the 825 patients on treatment for at least a year, the annualized relapse rate (ARR) decreased from median 2.0 [mean 2.01, 95% conﬁdence interval (CI) 1.92–2.11] in the year prior to natalizumab to 0.0 (mean 0.25, 95% CI 0.21–0.29) at 1 year (p \ 0.001). The Expanded Disability Status Scale (EDSS) score decreased from median 3.5 at baseline (mean 3.71, 95% CI 3.60–3.82) to 3.0 (mean 3.37, 95% CI 3.25–3.49) (p \ 0.0001). The discontinuation rate was 14%. One patient discontinued natalizumab due to progressive multifocal leukoencepha- lopathy (PML) and another due to probable PML (subse- quently conﬁrmed). Although our patients had more severe disease than those in the pivotal study, a similar reduction in ARR was observed. This ﬁnding is in line with previous observational studies. The effect was independent of base- line EDSS. Keywords Multiple sclerosis Natalizumab Observational study Spain Relapse Disability progression Introduction Natalizumab is a monoclonal antibody that interferes with leukocyte trafﬁcking into the central nervous system by antagonizing the a4 subunit of integrin expressed on the surface of activated T-cells [1, 2]. Such an action is thought to reduce the inﬂammatory component of multiple sclerosis (MS), particularly during the early relapsing–remitting phases of the disease [3]. A number of randomized con- trolled phase II and phase III studies have shown natal- izumab to be effective at reducing the annualized relapse rate (ARR) and also disease progression as measured using