Long-Term Efficacy Outcomes of Natalizumab vs. Fingolimod in Patients With Highly Active Relapsing-Remitting Multiple Sclerosis: Real-World Data From a Multiple Sclerosis Reference Center

Abstract

Background: Natalizumab (NTZ) and fingolimod (FTY) are second-line disease modifying treatments (DMTs) approved for Relapsing – Remitting Multiple Sclerosis (RRMS). Few studies are available on a direct comparison between NTZ and FTY, based on post-marketing experience, with conflicting results and reporting relatively short follow-up period.Aim: We hereby report real-world experience of a MS Center with respect to NTZ vs. FTY comparison in terms of efficacy and safety, referencing long-term follow-up.Methods: We used retrospective data for all patients that received 2nd-line treatment NTZ (since May 2007) or FTY (since September 2011). Primary endpoints were, among others, annual EDSS score (mean change from baseline), time to disability worsening or improvement, Annualized Relapse Rate (ARR) after 12 and 24 months and upon total treatment duration, time to first relapse and time to radiological progression.Results: A total of 138 unmatched patients, 84 treated with NTZ and 54 treated with FTY were included. Following Propensity Score (PS) matching, 31 patients in each group were retained. Mean follow-up period for NTZ- and FTY-treated patients was 4.43 ± 0.29 and 3.59 ± 0.32 years (p = 0.057), respectively. In the matched analysis, time to disability improvement and time to disability worsening was comparable between groups. A higher proportion of patients remained free of relapse under NTZ, compared to FTY (Log Rank test p = 0.021, HR: 0.25, 95% CI: 0.08–0.8), as well as free of MRI activity (Log Rank test p = 0.006, HR: 0.26, 95% CI: 0.08–0.6). Treatment discontinuation due to MRI activity was significantly higher for FTY-treated patients compared to NTZ (Log Rank test p = 0.019, HR: 0.12, 95% CI: 0.05–0.76).Conclusion: Our results indicate toward NTZ superiority with respect to relapse and MRI activity outcomes. The fact that NTZ-treated patients may achieve long-standing clinical and radiological remission points toward the need for long follow-up data.

Use of natalizumab in persons with multiple sclerosis: 2022 update

“…When initiated early in the disease course, natalizumab was associated with fewer relapses and reduced disability worsening (Butzkueven et al, 2020a;Wiendl et al, 2021). The long-term effectiveness of natalizumab was also described in other real-world studies (Boziki et al, 2021;Davidescu et al, 2021;Efthimios et al, 2021;Guger et al, 2021;Horakova et al, 2020;Prosperini et al, 2017). Results from these studies indicate that, when administered long-term, natalizumab is effective and has an adequate safety profile, provided subjects are closely monitored.…”

“…Real-world cohorts of persons with RRMS from single centers, multicenters, and national and international registries have been well utilized to explore the comparative effectiveness of natalizumab with another highly effective DMT, fingolimod, across clinical, radiological, disability, and disease activity outcomes (Barbin et al, 2016;Baroncini et al, 2016;Boziki et al, 2021;Braune et al, 2013;Curti et al, 2019;Guerra et al, 2021;Kalincik et al, 2015;Koch-Henriksen et al, 2017;Prosperini et al, 2017). The majority of these studies have shown natalizumab to be superior to fingolimod with regard to ARR, proportion of PwMS relapsing at 1 and 2 years and over longer time periods, short-term disability improvement, and proportions of PwMS with gadolinium (Gd)-enhancing lesions or new T2 lesions at 1 and 2 years (Barbin et al, 2016;Baroncini et al, 2016;Boziki et al, 2021;Kalincik et al, 2015).…”

“…Real-world cohorts of persons with RRMS from single centers, multicenters, and national and international registries have been well utilized to explore the comparative effectiveness of natalizumab with another highly effective DMT, fingolimod, across clinical, radiological, disability, and disease activity outcomes (Barbin et al, 2016;Baroncini et al, 2016;Boziki et al, 2021;Braune et al, 2013;Curti et al, 2019;Guerra et al, 2021;Kalincik et al, 2015;Koch-Henriksen et al, 2017;Prosperini et al, 2017). The majority of these studies have shown natalizumab to be superior to fingolimod with regard to ARR, proportion of PwMS relapsing at 1 and 2 years and over longer time periods, short-term disability improvement, and proportions of PwMS with gadolinium (Gd)-enhancing lesions or new T2 lesions at 1 and 2 years (Barbin et al, 2016;Baroncini et al, 2016;Boziki et al, 2021;Kalincik et al, 2015). Several studies use the metric of "no evidence of disease activity (NEDA) encompassing the absence of three clinical/imaging markers (NEDA-3)" -i.e., absence of relapses, no new radiological activity, and no confirmed disability progression (Wong et al, 2018) have shown a significantly higher proportion of PwMS treated with natalizumab than fingolimod achieved NEDA-3 at 2 years, with one study extending this observation to 4 years (Baroncini et al, 2016;Curti et al, 2019;Guerra et al, 2021;Prosperini et al, 2017).…”

“…Anti-JCV antibody seropositivity and increased risk for PML is the most common reason for natalizumab discontinuation (Boziki et al, 2021;Chisari et al, 2021;Coerver et al, 2021;Guger et al, 2021;Hersh et al, 2020;Karanasios et al, 2021). If JCV index is > 1.5, management options include extending the dosing interval of natalizumab or switching to an alternative DMT.…”

New Therapeutic Targets for Hepatic Fibrosis in the Integrin Family, α8β1 and α11β1, Induced Specifically on Activated Stellate Cells

“…Learned from the developmental history, not all, but many of the αv-inhibitors have an inherent nonspecific property with regard to binding of inhibitors to the target and engagement of the target integrin to ligands. In contrast, the integrin inhibitors already in the clinic, such as abciximab (targeting αIIbβ3 on platelets) [ 96 ], natalizumab (α4β1 on T-cells) [ 97 , 98 ], vedolizumab (α4β7 on T-cells) [ 99 ], and lifitegrast (αLβ2 on T-cells) [ 100 ] commonly bind specifically to their targets. Three of the inhibitors are target specific mAbs, and the other inhibitor, liftegrast, is localized in the site of pathology (dry eye) due to the nature of the ophthalmic solution.…”