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.
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).
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.
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.
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).