Background

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.

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

Background

Natalizumab (NTZ) and fingolimod (FTY) are effective treatments for patients with relapsing-remitting multiple sclerosis (RRMS), yet comparative randomised controlled trials (RCTs) of their effectiveness have been limited.

Objectives

To compare the effectiveness of NTZ versus FTY in a network meta-analysis (NMA) of studies in RRMS patients, including indirect evidence from RCTs and direct real-world evidence from non-randomized studies (NRSs).

Methods

RCTs and NRSs were identified in a systematic literature review of studies assessing the effectiveness of NTZ and FTY. An NMA was employed to synthesize the evidence. RCTs indirectly compared treatments via placebo. Outcomes evaluated at 2 years included relapse rate (3 RCTs, 10 NRSs), relapse free patients (3 RCTs, 7 NRSs), 6-month confirmed disability worsening (CDW) (3 RCTs, 3 NRSs), 6-month confirmed disability improvement (CDI) (2 RCTs, 3 NRSs), and no evidence of disease activity (NEDA-3; defined as no relapses, no CDW, and no active magnetic resonance imaging lesions) (2 RCTs, 5 NRSs). Incidence rate ratios (IRRs), odds ratios (ORs) and hazard ratios (HRs) summarised relative effects; values <1 favoured NTZ. Sensitivity analyses employed design-adjusted NMA models; NRSs were down-weighted according to their risk of bias with the ROBINS-I tool.

Results

The relapse rate (IRR [95% confidence interval (CI)]) was lower in patients treated with NTZ than with FTY in RCTs (0.67 [0.51–0.88]), NRSs (0.65 [0.50–0.85]) and the NMA (0.67 [0.55–0.82]). The probability (OR [95% CI]) of remaining relapse free was higher with NTZ than with FTY in RCTs (0.88 [0.62–1.25]), NRSs (0.48 [0.35–0.67]) and the NMA (0.52 [0.39–0.70]). The probability (OR [95% CI]) of CDW was lower with NTZ than with FTY in RCTs (0.66 [0.42–1.05]), NRSs (0.80 [0.54–1.17]) and the NMA (0.74 [0.55–0.99]). The probability (HR [95% CI]) of CDI was similar with NTZ and FTY in RCTs (0.98 [0.53–1.81]) but was higher with NTZ than with FTY in NRSs (0.52 [0.24–1.14]) and the NMA (0.59 [0.33–1.05]). NEDA-3 was more often achieved (OR [95% CI]) with NTZ than with FTY in RCTs (0.55 [0.32–0.93]), NRSs (0.38 [0.29–0.50]) and the NMA (0.41 [0.32–0.52]). Design-adjusted NMAs did not substantially alter the clinical interpretation of results.

Conclusions

NTZ was more effective than FTY across a range of key effectiveness measures. In the absence of head-to-head trials, these results provide evidence about the comparative effectiveness of NTZ and FTY.

This study is funded by Biogen. Biogen funded the analyses and writing support for this abstract. Writing support was provided by Ashfield Healthcare Communications (Middletown, CT, USA).

Background

Unemployment rates can be high among patients with multiple sclerosis (MS), and a return to work after unemployment can be difficult, highlighting the importance of treatment in preventing a departure from the workforce due to MS. Natalizumab is a highly effective treatment for patients with relapsing-remitting MS (RRMS) and was associated with positive employment outcomes in real-world studies.

Objectives

To evaluate changes in employment status in RRMS patients treated with natalizumab in the TYSABRI Observational Program (TOP), a large observational study assessing the long-term safety and effectiveness of natalizumab.

Methods

This retrospective analysis included patients aged ≤65 years at TOP enrolment (i.e., baseline [BL]) who were surveyed on their employment status in the year before natalizumab initiation and in the period since treatment initiation (N=2004). Multivariate logistic regression tested the association between BL characteristics and employment outcomes.

Results

At BL, patients had a mean (standard deviation [SD]) Expanded Disability Status Scale (EDSS) score of 3.5 (1.5). At the survey, patients had a mean (SD) of 5.5 (3.3) years of natalizumab treatment. Survey responses indicated that in the year before natalizumab initiation, 1107 patients (55.2%) were working; 814 patients (40.6%) were working full time, 53 (2.6%) were working part time due to MS, 265 (13.2%) were not working due to MS, and 240 (12.0%) and 632 (31.5%) were working part time or not at all, respectively, for other reasons. After natalizumab initiation, 861 patients (43.0%) improved (1.3%) or maintained (41.6%) their employment level, whereas 170 (8.5%) experienced a decline in employment level due to MS and 256 (12.8%) remained unemployed due to MS. Significant predictors of improving/maintaining employment status were younger age (adjusted odds ratio [aOR]: 0.756; P=0.005), lower BL EDSS score (aOR: 0.747; P<0.001), and fewer relapses in the year before natalizumab initiation (aOR: 0.829; P=0.042), but did not include sex, prior therapy use, or RRMS duration.

Conclusions

Of patients who were working prior to natalizumab initiation, 77.0% maintained or improved their employment level with an average follow up of 5.5 years. Overall, favourable outcomes were predicted by younger age and less BL disease activity, supporting the importance of natalizumab initiation early in the disease course to help prevent patients from leaving the workforce due to MS.

The TOP study is funded by Biogen. Biogen funded the analyses and writing support for this abstract. Writing support was provided by Ashfield Healthcare Communications (Middletown, CT, USA).

Background

Natalizumab (NTZ) and fingolimod (FTY) are effective treatments for patients with relapsing-remitting multiple sclerosis (RRMS), yet comparative randomised controlled trials (RCTs) of their effectiveness have been limited.

Objectives

To compare the effectiveness of NTZ versus FTY in a network meta-analysis (NMA) of studies in RRMS patients, including indirect evidence from RCTs and direct real-world evidence from non-randomized studies (NRSs).

Methods

RCTs and NRSs were identified in a systematic literature review of studies assessing the effectiveness of NTZ and FTY. An NMA was employed to synthesize the evidence. RCTs indirectly compared treatments via placebo. Outcomes evaluated at 2 years included relapse rate (3 RCTs, 10 NRSs), relapse free patients (3 RCTs, 7 NRSs), 6-month confirmed disability worsening (CDW) (3 RCTs, 3 NRSs), 6-month confirmed disability improvement (CDI) (2 RCTs, 3 NRSs), and no evidence of disease activity (NEDA-3; defined as no relapses, no CDW, and no active magnetic resonance imaging lesions) (2 RCTs, 5 NRSs). Incidence rate ratios (IRRs), odds ratios (ORs) and hazard ratios (HRs) summarised relative effects; values <1 favoured NTZ. Sensitivity analyses employed design-adjusted NMA models; NRSs were down-weighted according to their risk of bias with the ROBINS-I tool.

Results

The relapse rate (IRR [95% confidence interval (CI)]) was lower in patients treated with NTZ than with FTY in RCTs (0.67 [0.51–0.88]), NRSs (0.65 [0.50–0.85]) and the NMA (0.67 [0.55–0.82]). The probability (OR [95% CI]) of remaining relapse free was higher with NTZ than with FTY in RCTs (0.88 [0.62–1.25]), NRSs (0.48 [0.35–0.67]) and the NMA (0.52 [0.39–0.70]). The probability (OR [95% CI]) of CDW was lower with NTZ than with FTY in RCTs (0.66 [0.42–1.05]), NRSs (0.80 [0.54–1.17]) and the NMA (0.74 [0.55–0.99]). The probability (HR [95% CI]) of CDI was similar with NTZ and FTY in RCTs (0.98 [0.53–1.81]) but was higher with NTZ than with FTY in NRSs (0.52 [0.24–1.14]) and the NMA (0.59 [0.33–1.05]). NEDA-3 was more often achieved (OR [95% CI]) with NTZ than with FTY in RCTs (0.55 [0.32–0.93]), NRSs (0.38 [0.29–0.50]) and the NMA (0.41 [0.32–0.52]). Design-adjusted NMAs did not substantially alter the clinical interpretation of results.

Conclusions

NTZ was more effective than FTY across a range of key effectiveness measures. In the absence of head-to-head trials, these results provide evidence about the comparative effectiveness of NTZ and FTY.

This study is funded by Biogen. Biogen funded the analyses and writing support for this abstract. Writing support was provided by Ashfield Healthcare Communications (Middletown, CT, USA).