Prolonged release (PR) fampridine is indicated for the improvement of walking in adult multiple sclerosis (MS) patients. Several studies have supported that PR-fampridine improves walking ability in this population; however, reported effects have varied widely across studies and study design.
To conduct a systematic literature review (SLR) and meta-analysis (MA) to summarize the evidence on the efficacy and effectiveness of PR-fampridine in MS patients.
Following PRISMA guidelines, a systematic search of PubMed, EMBASE, YORK and Cochrane Library was conducted from January 1, 2006-April 1, 2019 to identify publications comparing the efficacy and effectiveness of PR-fampridine from Randomized Controlled Trials (RCTs) and observational studies (OBS). For RCTs, outcome measures include Timed 25-Foot Walk (T25FW) and 12-item Multiple Sclerosis Walking Scale (MSWS-12) responders and MSWS-12 scores; for OBS, T25FW walking time and MSWS-12 scores. In the MA, pooled estimates were derived using odds ratios (OR) and standardized mean differences (SMD) of both endpoints. Results from RCTs and OBS were reported separately using a random effects model.
Of a total of 897 unique citations, 27 studies met all criteria for inclusion in the MA, 9 RCTs and 18 single-arm OBS. A pooled estimate based on T25FW responder data from 4 RCTs showed statistically significant improvements in walking ability in the PR-fampridine vs. placebo group; OR (95% CI): 4.8 (2.9-7.9), p<0.0005. Also, findings based on MSWS-12 responder data from 2 RCTs showed significant improvements in walking ability in the PR-fampridine group vs. placebo; OR (95% CI): 1.7 (1.1-2.5); p=0.011. A pooled estimate of mean MSWS-12 scores from 4 RCTs also showed significant improvements in the PR-fampridine vs. placebo group; OR (95% CI): 1.5 (1.2-1.9); p<0.0005. Summary estimates from OBS suggest a significant improvement vs. baseline on T25FW time derived from 9 studies showing that walking time was significantly improved vs. baseline; with SMD (95% CI): –0.31 (-0.479 to -0.146); p<0.0005. Also, the pooled estimate from MSWS-12 endpoint in 6 studies showed that walking ability was statistically improved vs. baseline; SMD (95% CI): -0.98 (-0.892 to -1.058); p<0.0005.
Across randomized and observational data, the use of PR-fampridine is consistently associated with significantly improved walking ability in MS patients measured by MSWS-12 or T25FW endpoints.
This study is funded by Biogen. Biogen funded the analyses for this abstract.