Abstract
Background/objectives In the adaptive dose-ranging, 6- or 3-month BOLD study in patients with relapsing-remitting multiple sclerosis, once-daily siponimod (BAF312) showed dose-dependent reduction of combined unique active lesion number and annualized relapse rate (ARR); near-maximal effects were observed at 2 mg. Here, we report the efficacy findings of first 12 months of the extension (representing >18 or 15 months of total treatment). Design/methods Patients either continued on siponimod doses assigned in the core phase or were re-randomized from placebo to siponimod 10, 2, 1.25, 0.5 and 0.25 mg: 33, 29, 43, 29 and 50 patients comprised each dose group, respectively. Patients had >7 days (washout time) study drug interruption between core and extension phases to enable siponimod dose titration from 0.25 mg over the first 10 days. Magnetic resonance imaging (MRI) was performed at extension baseline, month 6 and month 12. Results 263/297 (88.6%) patients completed the core study; 184 of these (62.0%) entered the extension. The following data pertain to patients taking 10, 2, 1.25, 0.5 and 0.25 mg, respectively. 27, 25, 37, 24 and 37 patients had a 12-month MRI, and mean gadolinium-enhancing lesion numbers at extension month 12 were: 0.1, 0.5, 0.1, 0.6, 0.8 (compared with 1.7, 1.4, 1.8, 3.1, 1.3 at core study baseline, and 1.7 in placebo at month 6). Mean numbers of new/enlarged T2 lesions at extension month 12 were 0.4, 0.6, 0.2, 1.7 and 1.7, and ARRs were 0.27 (95% confidence interval, 0.14–0.52), 0.18 (0.08–0.42), 0.13 (0.06–0.28), 0.34 (0.18–0.64) and 0.33 (0.20–0.54). No new safety issues were observed. Conclusion Over the 12-month extension, MRI-assessed inflammatory lesion activity and ARRs remained low, particularly in the 1.25, 2 and 10 mg treatment groups, with no new safety concerns.
Published Version
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