Dalfampridine Utilization and Efficacy Assessment in Clinical Practice
Two phase 3 trials showed approximately 35% of patients receiving dalfampridine were Timed 25 Foot Walk (T25FW) responders, with average improvement in walking speed of 25%. We examined if T25FW response rate and magnitude differ in clinical practice.
To assess utilization of dalfampridine and magnitude of walking speed improvement in clinical practice.
Single-center retrospective study evaluating all patients for whom dalfampridine was prescribed since approval, from March 2010 through August 2013. Inclusion criteria for T25FW analyses: diagnosis of MS, dalfampridine treatment ≥ 3 months, and minimum of two T25FW measurements within one year pre- and post- treatment. Descriptive statistics were used for cohort characterization. Logistic regression was used to assess mean pre-T25FW time as a predictor of response.
Chart review identified 221 intention-to-treat (ITT) patients. Dalfampridine was shipped to 174 (78.7%), twelve of whom never began therapy. Thirty patients (13.5%) discontinued dalfampridine in < 3 months due to lack of subjective benefit. 67 patients (30.5%) had insufficient visits or documentation during the time window, and 6 patients (2.7%) were non-ambulatory at baseline. Fifty-three patients (23.9%) met our inclusion criteria for walking speed analysis, with mean T25FW of 9.5 seconds (range 3.8 to 66.3).
Twenty-nine of these patients (56.9%) showed improvement in T25FW speed, and 24 (53.8%) showed none. In 10 patients (18.9%), the T25FW improvement was < 10%. Eleven patients (20.8%) improved between 10 - 20%. Only 8 patients (15.1%) achieved a clinically meaningful threshold of > 20% improvement, comprising 3.6% of the 221 patients in the ITT population. Despite this, 47 of the 53 (88.7%) continued therapy at last point of follow up.
Mean baseline T25FW time was not a statistically significant clinical predictor for response to dalfampridine, controlling for age, gender and type of MS (p = .815).
Our real world cohort demonstrated a lower rate and magnitude of T25FW improvement than was seen in clinical trials. Given that only a small minority of patients who continued on dalfampridine showed a clinically meaningful T25FW improvement, the T25FW may be an insensitive measure of actual therapeutic response to dalfampridine. Pretreatment walking speed was not a clinical predictor of response to dalfampridine, suggesting that investigation of paraclinical measures may be of use.