Walking impairment in patients with multiple sclerosis - a new therapeutic approach and clinical potential of dalfampridine extended release tablets.

Abstract

Walking impairment is a clinical hallmark of multiple sclerosis (MS) that has been under-recognized as a therapeutic target for pharmacologic intervention. The development and approval of dalfampridine extended release tablets (dalfampridine-ER; known as prolonged-, modified, or sustained-release fampridine outside the USA), 10 mg taken twice daily, to improve walking in patients with MS, fills a previously unmet need. In three randomized, double-blind, placebo-controlled trials, dalfampridine-ER improved walking speed in approximately one-third (37%) of treated patients, and average walking speed on therapy among these responders improved by approximately 25% relative to baseline. Walking-speed improvement among responders was clinically significant, as determined by a statistically significant improvement in the patient-reported 12-item Multiple Sclerosis Walking Scale. Long-term extension studies indicate that responders were able to maintain benefits, compared with nonresponders over prolonged periods of treatment. Dalfampridine-ER was generally well tolerated. Dizziness, insomnia, balance disorder, headache, nausea, urinary tract infection, and asthenia were the most common adverse events. Although the incidence of seizures appeared to be dose related, among patients treated with dalfampridine-ER in the three trials, the rate of seizures was 0.25%. These efficacy and safety data suggest that dalfampridine-ER can be a useful and clinically relevant addition to the pharmacologic armamentarium for the management of MS symptoms and disabilities. Because of its narrow therapeutic index and potential for seizures, it is especially important in the clinical setting to adhere to the dosing recommended in the approved labels.