J Neurol (2012) 259:1814–1823 the Expanded Disability Status Scale (EDSS). In most cases, a substantial reduction in disease activity according to magnetic resonance imaging (MRI) measures has also been documented [4–7]. Natalizumab has been on the market in Spain since 2007, and as of July 2010, 1,865 patients had been treated. Natalizumab was approved largely on the strength of the pivotal AFFIRM study, which compared natalizumab infusions with placebo infusions in patients who for the most part had not received prior MS therapy [6]. However, in view of the risk of progressive multifocal leukoen- cephalopathy (PML)—developed by two patients in the SENTINEL study [7], which compared natalizumab versus the combination of natalizumab plus interferon b-1a IM— the indication was limited to patients who have failed front- line therapy or who have an aggressive form of the disease. As a consequence, patients treated in clinical practice tend to have more severe disease than those enrolled in the AFFIRM study [8–12]. The aim of this multicenter, retrospective study is to collect data on patients treated with natalizumab in Spain in everyday clinical practice and to compare the patient and disease characteristics both with those published in clinical trials and with other observational studies. Patients and methods All Spanish centers that had treated at least one patient with natalizumab before 31 May 2010 were invited to participate in the study. To be included, patients had to be diagnosed with MS and have received at least one dose of natalizumab prior to this cut-off date. All patients gave written informed consent for their data to be used in the study, which was approved by the Ethics Committees of the participating centers and notiﬁed to the Spanish Drug Agency. The investigators retrospectively ﬁlled out electronic data-col- lection forms (an Excel spreadsheet) for natalizumab-trea- ted patients from their clinical records. Data were transferred anonymously from the returned Excel forms to the database to safeguard the privacy of the patients. The data-collection forms included sections for demo- graphic data (sex and date of birth), baseline disease data [year of diagnosis of MS, prior treatments, clinical form of MS prior to initiation of natalizumab treatment, EDSS score prior to treatment with natalizumab, ARR prior to treatment with natalizumab, and MRI data (presence of T1 Gd-enhancing lesions and T2-hyperintense lesions prior to treatment)], details of natalizumab treatment (number of natalizumab perfusions), and disease data after initiating treatment (EDSS score at 6 and 12 months after starting treatment, ARR after 12 months of treatment, and MRI 1815 data after 12 months of treatment). In addition, safety data were collected (adverse drug reactions, neutralizing anti- bodies, hypersensitivity reactions, and reason for treatment withdrawal when applicable). Data from the forms were collected and analyzed by a contract research organization (Phidea Marvin, Madrid, Spain). Statistical analysis Descriptive statistics were calculated for patient data [mean, standard deviation (SD), minimum, median, maxi- mum for continuous variables, and percentages for cate- gorical variables]. Variables were compared using the McNemar test or the Wilcoxon test as appropriate, and statistical signiﬁcance was set at p \ 0.05. Analysis was performed with the SAS program. Results Data capture Data were collected from 86 Spanish centers, correspond- ing to an estimated 56% of all Spanish centers where na- talizumab is prescribed and accounting for approximately 85% of natalizumab prescriptions in Spain. Data were available for 1,415 patients. Fifty-one patients were excluded from the subsequent analyses because of inconsistency in the data (36 patients), ﬁrst administration of natalizumab before the patient’s 18th birthday (14 patients), or missing number of infusions (one patient). The ﬁnal number of patients analyzed was there- fore 1,364. Patient characteristics In the year prior to treatment the median ARR was 2.0 (range 1–14) (mean 2.01, 95% CI 1.94–2.08). The median EDSS score at baseline was 3.5 (mean 3.77, 95% CI 3.68–3.86). Most patients had EDSS between 2 and 3 [478/ 1,318 (36.3%)] and between 3.5 and 4.5 [349/1,318 (26.5%)]. Fifty-three patients (4.0%) had baseline EDSS [6 points. The patients included predominantly had the relapsing–remitting form (87%); the remainder had sec- ondary progressive MS with relapses. A large majority of patients had received prior MS treatment [1,268/1,363 (93.0%)], and the median duration of this prior treatment was 52 months (range 0–258 months). Subcutaneous (SC) interferon beta 1a was the most common prior treatment, followed by interferon beta 1b SC (Table 1). In total, 603 patients (44.2%) had received only one prior treatment while 665 (48.8%) had 123