J Neurol (2012) 259:1814–1823 Outcome measure Annualized relapse ratea Percentage of patients with at least one relapsea Basal EDSS score Patients with Gd-enhancing lesions at baseline Table 2 Efﬁcacy outcomes for patients on treatment for at least 12 months Baseline n 826 826 839 563 Value Median 2.0 (0–14) Mean 2.01 (1.92–2.11) 733 (88.7%) Median 3.50 (0–8.5) Mean 3.71 (3.60–3.82) 289 (51.3%) At 12 months/during 12-month treatment period n 825 825 839 563 Value Median 0.0 (0–4)b Mean 0.25 (0.21–0.29) 168 (20.4%) 3.00 (0–7.5)c Mean 3.37 (3.25–3.49) 33 (5.9%) 1817 Results presented as median (range), mean (95% conﬁdence interval), or absolute number (%) EDSS Expanded Disability Status Scale a In the year prior to baseline b p \ 0.001 versus baseline (Wilcoxon test) c p \ 0.001 versus baseline (McNemar test) Concomitant infections were reported by 144 patients out of 1,283 with data available (11.2%) during natalizumab treatment; none of these were considered severe. Efﬁcacy outcomes For patients who completed at least 12 months of treat- ment, the median ARR decreased from 2.0 (mean 2.01, 95% CI 1.92–2.11) in the year prior to treatment to 0.0 (mean 0.25, 95% CI 0.21–0.29) during the 12-month treatment period [p \ 0.0001 (McNemar test)] (Table 2). On stratiﬁcation by baseline EDSS, similar decreases were observed across the different initial disease severities (Fig. 1). In addition, the percentage of patients with at least one relapse decreased from 89% in the year prior to treatment to 20% in the year after starting treatment. The EDSS score also decreased [from median 3.5 at baseline to 3.0 at 12 months (p \ 0.0001, Wilcoxon test), mean from 3.71 (95% CI 3.60–3.82) at baseline to 3.37 (95% CI 3.25–3.49) at 12 months] (Table 2). Twenty-four percent of the patients showed improvement in EDSS (deﬁned as a decrease of C1.0 point) and only 6% showed worsening (deﬁned as an increase of C1.0 point) between baseline and 1 year after treatment [Table 3, p \ 0.0001 for the differences (McNemar test)], the rest (70%) remaining stable. Less than half the patients were free of Gd-enhancing lesions in the year prior to starting natalizumab treatment (Table 2), whereas in the year following start of treatment, 96.4% were free of such lesions [p \ 0.0001 (McNemar test)]. Only 23/289 patients (8.0%) with baseline Gd- enhancing lesions still had Gd-enhancing lesions after 1 year of treatment, whereas 10/274 patients (3.7%) with- out baseline Gd-enhancing lesions developed such lesions after 1 year of treatment. After 1 year of treatment, 84.5% of patients were free of new T2-hyperintense lesions. Fig. 1 Change in annualized relapse rate (year prior to and year after starting natalizumab treatment for all patients in treatment for at least 12 months) by baseline Expanded Disability Status Scale score. Percentages indicate relative reductions in the ARR between the year before treatment and the year on treatment Table 3 Summary of change in disease status according to Expanded Disability Status Scale score Time period relative to baseline -12–0 months 0–6 months 6–12 months Change in disease status Improvement Stability Worsening 3.55 68.14 28.31 Improvement deﬁned as decrease C1 point on Expanded Disability Status Scale, stability as \1 point change, and worsening as increase C1 point over time. Only patients in treatment for 12 months inclu- ded. The differences were statistically signiﬁcant [p \ 0.0001 (McNemar test)] We deﬁned a variable ‘‘disease free’’ as patients without any of the following: worsening EDSS (C1 point increase), presence of relapses, and presence of Gd-enhancing and 17.52 78.68 3.8 23.77 69.98 6.25 123