Faculty Bibliography

OBJECTIVE: A previous phase 3 study showed significant improvement in walking ability in multiple sclerosis (MS) patients treated with oral, extended-release dalfampridine (4-aminopyridine) 10mg twice daily. The current study was designed to confirm efficacy and further define safety and pharmacodynamics. METHODS: This was a 39-center, double-blind trial in patients with definite MS of any course type. Participants were randomized to 9 weeks of treatment with dalfampridine (10mg twice daily; n = 120) or placebo (n = 119). Response was defined as consistent improvement on the Timed 25-Foot Walk, with percentage of timed walk responders (TWRs) in each treatment group as the primary outcome. The last on-treatment visit provided data from 8 to 12 hours postdose, to examine maintenance of effect. RESULTS: One patient from each group was excluded from the modified Intention to Treat population. The proportion of TWRs was higher in the dalfampridine group (51/119 or 42.9%) compared to the placebo group (11/118 or 9.3%, p < 0.0001). The average improvement in walking speed among dalfampridine-treated TWRs during the 8-week efficacy evaluation period was 24.7% from baseline (95% confidence interval, 21.0-28.4%); the mean improvement at the last on-treatment visit was 25.7%, showing maintenance of effect over the interdosing period. There were no new safety findings. INTERPRETATION: This interventional study provides class 1 evidence that dalfampridine extended-release tablets produce clinically meaningful improvement in walking ability in a subset of people with MS, with the effect maintained between doses

Pediatric multiple sclerosis (MS) accounts for up to 5% of all MS cases. Work conducted over the past 5 years has provided new information about the treatment, pathogenesis, demographics, and natural history of this disorder. Genetic and environmental factors seem to exert critical influences on its development. Clinical, MRI and laboratory data from prepubertal and postpubertal children suggest differences between the immune response and/or CNS environment in younger compared with older children and adults with MS. Randomized, controlled treatment trials for pediatric MS have not yet been performed, but therapies used in adult MS have been evaluated in this population, and their use seems to be safe. This article provides a comprehensive review of current knowledge regarding pediatric MS, highlighting new advances in the field.